trimethoprim--sulfamethoxazole-drug-combination and HIV-Infections

Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX.. We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies.. We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > .05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7-11.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1-34.2; I2 = 0.0%; P < .01) or P-C (13.7%; 95% CI, 9.8-18.8; I2 = 32.0%; P = .031). These results were consistent in analyses restricted to RCT data.. TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines.

Topics: Encephalitis; HIV Infections; Humans; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.. A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.. The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.. A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.. The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.. The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.

Topics: Aged; Diabetes Mellitus; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic fungal infection that occurs in people with impaired or suppressed immunity such as patients with human immunodeficiency virus or organ transplant. However, the incidence and characteristics of PCP in the population with long-term hemodialysis is poorly described in the literature.. We present a case of a 50-year-old female patient being transferred to our hospital in February 2022 with a 20-day history of cough and tight breath. She received amoxicillin and cephalosporin anti-infection treatment successively in local hospital but no significant improvement in symptoms. She had a 2-year history of hemodialysis and no relevant transplantation and human immunodeficiency virus infection. She was diagnosed as ANCA associated vasculitis (AAV) and given oral prednisone acetate (20 mg/day) and methotrexate (2.5 mg/week) half a year ago.. Based on the patient's medical history, Lung computerized tomography image, the Next generation sequencing report, the patient was diagnosed with renal failure, anti-neutrophil cytoplasmic antibody associated vasculitis, and Pneumocystis pneumonia.. The dosage of immunosuppressant was reduced due to leucocyte dripping and fever, and antibiotic and antifungal treatment were also given. The patient's lung condition was getting worse and noninvasive ventilator was required to maintain blood oxygen. Blood filtration is used to remove toxins. Ganciclovir and trimethoprim-sulfamethoxazole was used based on the next generation sequencing report.. The patient died of respiratory failure.. The risk of PCP in hemodialysis patients may be higher than that in ordinary population, and the prognosis of patients with immunosuppression may be worse. Dynamic assessment of vasculitis activity is necessary for hemodialysis patients with AAV because infections may obscure lung symptoms of AAV. It is not recommended that hemodialysis patients with long-term immunosuppression should reduce or stop the dosage of immunosuppressive drugs during the treatment because it may aggravate the condition of PCP. There is still no clear conclusion on whether hemodialysis patients need preventive medicine, but the identification of risk factors and early diagnosis and treatment are important for the prognosis of PCP on hemodialysis population.

Topics: Anti-Infective Agents; Female; HIV Infections; HIV Seropositivity; Humans; Immunosuppressive Agents; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often delayed and illness is associated with increased mortality.. To provide a comprehensive review of clinical presentation, risk factors, diagnostic strategies, and treatment options for PCP in patients without HIV infection.. Web-based literature review on PCP for trials, meta-analyses, and systematic reviews using PubMed. The restriction to the English language was applied.. Common underlying conditions in patients without HIV infection having PCP are haematological malignancies, autoimmune and inflammatory diseases, solid organ or haematopoietic stem cell transplant, and previous corticosteroid exposure. New risk groups include patients receiving monoclonal antibodies and immunomodulating therapies. Patients without HIV infection who have PCP present with rapid onset and progression of pneumonia, increased duration of hospitalization and a significantly higher mortality rate than patients infected with HIV. PCP is diagnosed by a combination of clinical symptoms and radiological as well as mycological features. Results of immunofluorescence microscopy from bronchoalveolar lavage, PCR testing, and computed tomography imaging as well as the evaluation of clinical presentation are required. The established treatment regime consists of trimethoprim and sulfamethoxazole.. Although the number of patients with immunosuppression due to causes different from HIV is increasing, a simultaneous rise in PCP incidence is observed. In the group of patients without HIV infection, rapid onset of symptoms, a more complex course, and a high mortality rate are recorded. Therefore, the time to diagnosis must be as short as possible to initiate effective therapy promptly. This review aims to raise awareness of PCP in an increasingly affected at-risk group and provides clinicians with a practical guide for efficient diagnosis and targeted therapy. Furthermore, it intends to display current inadequacies in research on the topic of PCP.

Topics: Bronchoalveolar Lavage; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.. We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.. We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.. Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.. In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.

Topics: Anti-Infective Agents; Child; Female; HIV Infections; Humans; Infant; Malaria; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; World Health Organization

Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa.. A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I. Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88-4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61-1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13-1.35), male gender (AHR = 1.43, 95% CI: 1.22-1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34-3.23), anemia (AHR = 1.73, 95% CI: 1.34-2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08-2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08-2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3-0.77).. In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people.

Topics: Adult; Africa South of the Sahara; Child; HIV Infections; Humans; Incidence; Isoniazid; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

This comprehensive review explores the intricate relationship between 2 major global health challenges, malaria and HIV, with a specific focus on their impact on children. These diseases, both endemic in sub-Saharan Africa, create a dual burden that significantly elevates the risk of morbidity and mortality, particularly in children with compromised immune systems due to HIV. The review delves into the complex mechanisms by which these infections interact, from heightened clinical malaria frequencies in HIV-infected individuals to the potential impact of antiretroviral therapy on malaria treatment. Different research engines were utilized in writing this paper such as Web of Science, Google Scholar, Pubmed Central, ResearchGate, and Academia Edu. To address this critical health concern, the study identifies and discusses various regulatory and treatment strategies. It emphasizes the importance of daily cotrimoxazole prophylaxis and insecticide-treated nets in preventing malaria in children with HIV. The potential of antiretroviral protease inhibitors and mRNA-based vaccines as innovative solutions is highlighted. Additionally, the study underscores the significance of climate data and artificial intelligence in improving diagnostics and drug development. Furthermore, the review introduces the concept of genetically modified mosquitoes as a novel approach to vector control, offering a promising avenue to protect HIV-positive individuals from mosquito-borne diseases like malaria. Through a comprehensive analysis of these strategies, the study aims to provide a foundation for policymakers, healthcare professionals, and researchers to develop effective regulations and interventions that reduce the dual burden of malaria and HIV in children, improving public health outcomes in endemic regions.

Topics: Animals; Antimalarials; Artificial Intelligence; Child; HIV Infections; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination

WHO first recommended cotrimoxazole prophylaxis for all infants who are HIV-exposed but uninfected (HEU) in 2000, given the ability of this treatment to prevent mortality from pneumocystis pneumonia in adults living with HIV. Over the last 21 years, evidence has been generated from the use of cotrimoxazole prophylaxis in infants who are HEU, including two randomised controlled trials, which have shown no clinical benefit and an increase in antibiotic resistance and microbiome dysbiosis. Additionally, improvements in health care over the last two decades in terms of antiretroviral treatment and prophylaxis for mothers and infants, and notably improved vaccination programmes, have substantially reduced the risk of HIV transmission and the overall morbidity and mortality of infants who are HEU from pneumonia and diarrhoeal diseases. Here, we highlight these changes in health care alongside the unchanged cotrimoxazole prophylaxis guidelines and call for a change in these guidelines on the basis of a public health and ethics approach.

Topics: Adult; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Severe drug hypersensitivity reactions to antibiotics are rare but trimethoprim-sulfamethoxazole (TMP-SMX) is uniquely associated with numerous and varied manifestations including a reaction resembling septic shock, first observed in human immunodeficiency virus (HIV)/AIDS patients. Over the past 25 years about 20 cases have been reported and an association with the virus and related immune system dysregulation was assumed. However, recent reports in adults have recognized similar shock-like reactions in non-HIV infected individuals. Here we review severe TMP-SMX hypersensitivity reactions and within the context of these known reactions, describe three non-HIV infected adolescent patients with shock-like reactions to TMP-SMX observed in one institution over 1.5 years.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Paracoccidioidomycosis (PCM) is an infection caused by fungi of the genus Paracoccidioides and is marked by a strong predilection for men; nevertheless, some women have had developed PCM and have presented oral involvement by the disease.. To review all published cases until August 2020 of oral PCM in women, with emphasis on the presence of systemic changes, deleterious habits (tobacco and alcohol) and oral manifestation features through a systematic review.. Observational studies (both prospective and retrospective) and case reports indexed in the Embase, PubMed, Scopus, Web of Science and LIVIVO databases were selected by two reviewers in a two-phase process following the pre-established PICOS criteria.. Twenty-five studies met the eligibility criteria and were selected for qualitative synthesis, of which 72 participants were enrolled. Brazilian White women between 40 and 50 years were the most affected and social history revealed them to be housewives or rural workers. Fifteen women (33.3% of the informed cases) presented any systemic change at the time of PCM diagnosis, namely pregnancy, HIV infection and/or depression. Moriform stomatitis was predominant and affected preferentially the gingivae and alveolar processes in the form of a single painful lesion. Most patients were treated with sulfamethoxazole + trimethoprim or itraconazole.. Oral PCM in women is rare; some cases showed systemic changes at the time of PCM diagnosis, namely HIV infection, pregnancy and depression. New studies should be conducted to elucidate the influence of systemic alterations on the development of oral PCM in women.

Topics: Adult; Brazil; Coinfection; Databases, Factual; Female; HIV Infections; Humans; Itraconazole; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Atovaquone; CD4 Lymphocyte Count; CD4-CD8 Ratio; COVID-19; Dideoxynucleosides; Female; Glucocorticoids; Graft Rejection; HIV Infections; HIV-1; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lamivudine; Male; Middle Aged; Mycophenolic Acid; Pneumonia, Pneumocystis; Prednisolone; Raltegravir Potassium; RNA, Viral; SARS-CoV-2; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity in immunocompromised patients, with a higher mortality in non-HIV than in HIV patients. P. jirovecii is one of the rare transmissible pathogenic fungi and the only one that depends fully on the host to survive and proliferate. Transmissibility among humans is one of the main specificities of P. jirovecii. Hence, the description of multiple outbreaks raises questions regarding preventive care management of the disease, especially in the non-HIV population. Indeed, chemoprophylaxis is well codified in HIV patients but there is a trend for modifications of the recommendations in the non-HIV population. In this review, we aim to discuss the mode of transmission of P. jirovecii, identify published outbreaks of PCP and describe molecular tools available to study these outbreaks. Finally, we discuss public health and infection control implications of PCP outbreaks in hospital setting for in- and outpatients.

Topics: Chemoprevention; Cross Infection; Disease Outbreaks; HIV Infections; Humans; Immunocompromised Host; Infection Control; Mycological Typing Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

A fixed dose of trimethoprim-sulphamethoxazole (TMP/SMZ) is the first-line therapy for Pneumocystis jirovecii pneumonia (PJP). Other alternative regiments have shown a suboptimal cure rate. However, TMP/SMZ has been reported to cause haemolyses when administered to patients with G6DP deficiency. PJP might be fatal without treatment. To date, there is still insufficient evidence to manage PJP with TMP/SMZ in G6DP deficiency population.. We report a G6PD-deficient patient with human immunodeficiency virus (HIV) and PJP infection treated successfully with 21 days of high dose TMP/SMZ without any signs and symptoms of haemolysis.. Based on our experience, it is worth to note that despite TMP/SMZ is consider unsafe in patient with pre-existing G6PD-deficiency, it could still be suggested as the initial drug of choice in Taiwanese or southeast Asian population for treating PJP infected HIV patient.

Topics: Adult; Anti-Bacterial Agents; Glucosephosphate Dehydrogenase Deficiency; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is an opportunistic disease that mainly affects patients with a deficiency of cell-mediated immunity, especially acquired immunodeficiency syndrome (AIDS). The incidence of PCP in these patients has declined substantially owing to the widespread use of antiretroviral therapy and PCP prophylaxis. However, PCP is still a major AIDS-related opportunistic infection, particularly in patients with advanced immunosuppression in whom human immunodeficiency virus type 1 (HIV-1) infection remains undiagnosed or untreated. The clinical manifestations, diagnosis, treatment, and prevention of PCP in patients with HIV-1 infection are addressed in this review.

Topics: Anti-Bacterial Agents; Biomarkers; HIV Infections; HIV-1; Humans; Immunity, Cellular; L-Lactate Dehydrogenase; Mucin-1; Opportunistic Infections; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.

Topics: Anti-Bacterial Agents; HIV Infections; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.. To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.. We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.. Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.. Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.. Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo.Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes.When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I. Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women.

Topics: Abortion, Spontaneous; Africa South of the Sahara; Antimalarials; Dizziness; Drug Combinations; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant, Low Birth Weight; Insecticide-Treated Bednets; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

The HIV epidemic continues to be a major global public health issue. Since 2012, there has been a paucity of information from the Republic of the Congo on HIV incidence and prevalence rates, national HIV programme effectiveness, highly active antiretroviral therapy (HAART) rollout, patient adherence to treatment, operational and basic science research studies on HIV/AIDS, and donor funding and its impact on the country. A review of the existing literature on HIV in the Republic of the Congo was conducted, focused on prevalence trends, effectiveness of the current national HIV programme, HAART rollout, patient adherence to antiretrovirals (ARVs), resistance to ARVs, the cost of treatment, and operational issues affecting HIV/AIDS programmes in the country. In light of the findings, several important priority areas for scaling-up HIV/AIDS services, programmatic and research activities in the Republic of the Congo are highlighted.

Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Congo; Health Services; HIV Infections; Humans; Incidence; Infectious Disease Transmission, Vertical; Medication Adherence; Prevalence; Program Evaluation; Sustainable Development; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Severe systemic reactions resembling septic shock have been described following trimethoprim-sulfamethoxazole (TMP-SMX) administration. Nearly all cases described in the literature occurred in HIV-infected patients.. We present a 42-year-old woman with a history of systemic lupus erythematosus (SLE) who was admitted to the Intensive Care Unit (ICU) twice with fever and circulatory shock after taking a dose of TMP-SMX 800-160 mg. She had no respiratory distress, urticarial rash or eosinophilia on presentation. Infectious workup during both admissions was negative and treatment with antibiotics, steroids and vasopressors was de-escalated with clinical improvement. She was found to be HIV negative, however, labs revealed a low CD4+ count.. TMP-SMX can rarely result in a severe, non-anaphylactic circulatory shock; if initially unrecognized, patients may undergo repeat drug exposure with an associated high morbidity risk. While more commonly reported in HIV individuals, this case demonstrates that TMP-SMX related circulatory shock can occur in a HIV negative patient.

Topics: Adult; Anti-Bacterial Agents; Female; HIV Infections; Humans; Lupus Erythematosus, Systemic; Shock; Trimethoprim, Sulfamethoxazole Drug Combination

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA.. Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines.. A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions.. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials.

Topics: Africa South of the Sahara; Anti-Bacterial Agents; Anti-Retroviral Agents; Counseling; HIV Infections; Home Care Services; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV-negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV-positive children.. To summarise the effects of TB preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017.. We included trials of HIV-positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo.. Two review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE.. We included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV-positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported.In HIV-positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups.. Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV-positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. .

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Child; HIV Infections; Humans; Incidence; Isoniazid; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

Topics: Anti-Infective Agents, Urinary; Chemoprevention; HIV Infections; Humans; Incidence; Recurrence; Secondary Prevention; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent.. We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models.. Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97).. The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.

Topics: Adult; Antiprotozoal Agents; Clindamycin; Cohort Studies; Female; HIV Infections; Humans; Male; Middle Aged; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

HIV-infected persons are particularly susceptible to the development of severe pneumococcal disease, even in the setting of combination antiretroviral therapy (cART), due to slow, incomplete recovery of anti-pneumococcal host defenses. This risk is increased by avoidable aspects of lifestyle, particularly smoking, which intensify immunosuppression. Clearly, more effective preventive measures are needed to counter this threat. Areas covered: This is a detailed review of the published literature focusing on currently available strategies for prevention of pneumococcal infection in HIV-infected patients, including cotrimoxazole prophylaxis, cART, pneumococcal vaccination, and smoking cessation strategies. This is preceded by a consideration of the epidemiology, clinical presentation, risk factors, and outcome of pneumococcal disease. Expert commentary: Cotrimoxazole prophylaxis has been shown to reduce morbidity and mortality in HIV-infected patients, although there is inconsistent data on the preventive efficacy against pneumococcal infections. Some recent studies have documented unchanged incidences of IPD in adult patients in the cART era. With regard to pneumococcal vaccination, routine acceptance of the efficacy of the PCV13/PPV23 sequential administration prime-boost strategy awaits the outcome of clinical trials in those with HIV infection. Smoking cessation, and discontinuation of excessive alcohol consumption and intravenous drug abuse, are priority strategies to prevent severe pneumococcal infection.

Topics: Adult; Anti-Bacterial Agents; HIV Infections; Humans; Incidence; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Smoking; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Resistance, Microbial; HIV Infections; Humans; Molecular Diagnostic Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole is an inexpensive, broad-spectrum antimicrobial drug that is widely used in developing countries. Before antiretroviral therapy (ART) scale-up, co-trimoxazole prophylaxis reduced morbidity and mortality in adults and children with HIV by preventing bacterial infections, diarrhoea, malaria, and Pneumocystis jirovecii pneumonia, despite high levels of microbial resistance. Co-trimoxazole prophylaxis reduces early mortality by 58% (95% CI 39-71) in adults starting ART. Co-trimoxazole provides ongoing protection against malaria and non-malaria infections after immune reconstitution in ART-treated individuals in sub-Saharan Africa, leading to a change in WHO guidelines, which now recommend long-term co-trimoxazole prophylaxis for adults and children in settings with a high prevalence of malaria or severe bacterial infections. Co-trimoxazole prophylaxis is recommended for HIV-exposed infants from age 4-6 weeks; however, the risks and benefits of co-trimoxazole during infancy are unclear. Co-trimoxazole prophylaxis reduces anaemia and improves growth in children with HIV, possibly by reducing inflammation, either through direct immunomodulatory activity or through effects on the intestinal microbiota leading to reduced microbial translocation. Ongoing trials are now assessing the ability of adjunctive co-trimoxazole to reduce mortality in children after severe anaemia or severe acute malnutrition. In this Review, we discuss the mechanisms of action, benefits and risks, and clinical trials of co-trimoxazole in developing countries.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antimalarials; Chemoprevention; Clinical Trials as Topic; Developing Countries; HIV Infections; Humans; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (CTX) prophylaxis is among the key interventions provided to HIV-infected individuals in resource-limited settings. We conducted a systematic review of the available evidence.. MEDLINE, Embase, Global Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included articles addressed impact of CTX prophylaxis on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the quality of evidence in individual articles and assessed the overall quality of the body of evidence, the expected impact, and the cost effectiveness (CE) for each outcome.. Of the initial 1418 identified articles, 42 met all inclusion criteria. These included 9 randomized controlled trials, 26 observational studies, 2 systematic reviews with meta-analysis, 1 other systematic review, and 4 CE studies. The overall quality of evidence was rated as "good" and the expected impact "high" for both mortality and morbidity. The overall quality of evidence from the 4 studies addressing retention in care was rated as "poor," and the expected impact on retention was rated as "uncertain." The 4 assessed CE studies showed that provision of CTX prophylaxis is cost effective and sometimes cost saving. No studies addressed impact on quality of life or HIV transmission.. CTX prophylaxis is a cost-effective intervention with expected high impact on morbidity and mortality reduction in HIV-infected adults in resource-limited settings. Benefits are seen in both pre-antiretroviral therapy and antiretroviral therapy populations.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cost-Benefit Analysis; Developing Countries; Health Impact Assessment; Health Resources; HIV Infections; Humans; Income; Outcome Assessment, Health Care; Quality of Life; Trimethoprim, Sulfamethoxazole Drug Combination

HIV-infected adults are at increased risk of severe malaria and death. Malaria prevention in people living with HIV (PLHIV) consists of several interventions, including cotrimoxazole (CTX) prophylaxis and insecticide-treated nets (ITNs). We conducted a systematic review of the available evidence.. MEDLINE, EmBase, Global Health, CINAHL, SOCA, and African Index Medicus were used to identify articles relevant to the CTX prophylaxis and ITNs interventions from 1995 to July 2014. For each individual study, we assessed the quality of evidence and the impact of the 2 interventions on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. For each outcome, we summarized the quality of the overall body of evidence, the expected impact, and costing and cost-effectiveness (CE).. The overall quality of evidence regarding malaria-related morbidity was rated as "good" for CTX prophylaxis and "fair" for ITN use; the expected "impact" of these interventions on morbidity was rated "high" and "uncertain," respectively. Three studies that addressed the costing and CE of ITN provision for malaria prevention in PLHIV consisted of 2 full "level 1" and 1 partial "level 2" economic evaluations.. CTX prophylaxis is effective in reducing malaria-related morbidity among PLHIV. Limited evidence is available with respect to the impact and the CE of ITN use and/or provision in this population.

Topics: Adult; Antimalarials; Cost-Benefit Analysis; Developing Countries; Health Impact Assessment; Health Resources; HIV Infections; Humans; Insecticide-Treated Bednets; Malaria; Morbidity; Outcome Assessment, Health Care; Quality of Life; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose.. We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163.. 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per μL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per μL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per μL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39).. Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per μL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings.. None.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Cost-Benefit Analysis; Drug Administration Schedule; Female; HIV Infections; Humans; Infant, Newborn; Male; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Pregnancy; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Antiretroviral therapy (ART) is the main intervention needed to reduce morbidity and mortality and to prevent tuberculosis in adults living with HIV. However, in most resource-limited countries, especially in sub-Saharan Africa, ART is started too late to have an effect with substantial early morbidity and mortality, and in high tuberculosis burden settings ART does not reduce the tuberculosis risk to that reported in individuals not infected with HIV. Co-trimoxazole preventive therapy started before or with ART, irrespective of CD4 cell count, reduces morbidity and mortality with benefits that continue indefinitely. Isoniazid preventive therapy as an adjunct to ART prevents tuberculosis in high-exposure settings, with long-term treatment likely to be needed to sustain this benefit. Unfortunately, both preventive therapies are underused in low-income and high-burden settings. ART development has benefited from patient-centred simplification with several effective regimens now available as a one per day pill. We argue that co-trimoxazole and isoniazid should also be combined into a single fixed-dose pill, along with pyridoxine (vitamin B6), that would be taken once per day to help with individual uptake and national scale-up of therapies.

Topics: Adult; Africa South of the Sahara; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Coinfection; Drug Combinations; Female; HIV Infections; HIV-1; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Tablets; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Vitamin B 6

Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.. Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.. Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.. The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Female; HIV Infections; Humans; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination

Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking.. Initiated by WHO, a panel of experts in BU and HIV management developed guidance principles for the management of BU-HIV co-infection based on review of available scientific evidence, current treatment experience, and global recommendations established for management of HIV infection and tuberculosis.. The expert panel agreed that all BU patients should be offered quality provider-initiated HIV testing and counselling. In areas with high prevalence of malaria and/or bacterial infections, all patients with HIV co-infection should be started on cotrimoxazole preventative therapy. Combination antibiotic treatment for BU should be commenced before starting antiretroviral therapy (ART) and provided for 8 weeks duration. The suggested combination is rifampicin (10 mg/kg daily up to a maximum of 600 mg/day) plus streptomycin (15 mg/kg daily). An alternative regimen is rifampicin plus clarithromycin (7.5 mg/kg twice daily up to a maximum of 1000 mg daily) although due to drug interactions with antiretroviral drugs this regimen should be used with caution. ART should be initiated in all BU-HIV co-infected patients with symptomatic HIV disease (WHO clinical stage 3 or 4) regardless of CD4 cell count and in asymptomatic individuals with CD4 count ≤500 cells/mm(3) . If CD4 count is not available, BU-HIV co-infected individuals with category 2 or 3 BU disease should be offered ART. For eligible individuals, ART should be commenced as soon as possible within 8 weeks after commencing BU treatment, and as a priority in those with advanced HIV disease (CD4 ≤ 350 cells/mm(3) or WHO stage 3 or 4 disease). All co-infected patients should be actively screened for tuberculosis before commencing BU treatment and before starting ART. Programmes should implement a monitoring and reporting system to document the outcomes of BU-HIV interventions.. Knowledge of the clinical and epidemiological interactions between BU and HIV disease is limited. While awaiting more urgently needed evidence, current management practice of both diseases has been useful to build simple 'common sense' preliminary guidance on how to manage BU-HIV co-infection.

Topics: Africa; Anti-Bacterial Agents; Anti-HIV Agents; Buruli Ulcer; CD4 Lymphocyte Count; Coinfection; Endemic Diseases; Guidelines as Topic; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa.. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses.. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire.. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.

Topics: Africa South of the Sahara; Antimalarials; Child; Drug Combinations; Drug Resistance; HIV Infections; Humans; Malaria; Mutation; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Female; HIV Infections; Humans; Insecticide-Treated Bednets; Malaria; Mefloquine; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low- and middle-income countries through a systematic review and meta-analysis.. PubMed and Embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in HIV-infected individuals aged ≥ 13 years on cotrimoxazole and ART and on ART alone. The Newcastle-Ottawa Quality Assessment Scale was used to assess selection, confounding and measurement bias. Publication bias was assessed using Egger's and Begg's tests. Sensitivity analysis was performed because the I-squared statistic indicated substantial heterogeneity in study results. A random-effects model was used for meta-analysis.. Nine studies were included. Begg and Egger P-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. The I-squared statistic was 93.2%, indicating high heterogeneity in study results. The sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with World Health Organization stage 3 or 4 HIV disease at baseline explained the heterogeneity. The summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29-0.61). Since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after ART-induced immune reconstitution.. Cotrimoxazole significantly increased survival in HIV-infected adults on ART. Further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients.

Topics: Anti-HIV Agents; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Confidence Intervals; Global Health; HIV Infections; Humans; Mortality; Odds Ratio; Statistics as Topic; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Despite the dramatic decrease in opportunistic infections after the introduction of highly active antiretroviral therapy, Pneumocystis jirovecii pneumonia remains the major AIDS related infection in France.. The clinical, radiological and microbiological diagnosis is usually easily made in HIV-infected patients. The preferred treatment is high dose trimethoprim-sulfamethoxazole, in association with steroids in cases of severe hypoxaemia. This has led to a dramatic reduction in mortality in these patients. Prophylactic treatment is mandatory in highly immunosuppressed patients (CD4 counts<200/μL) whose viraemia is not well controlled by antiretroviral therapy.. Whether PCR-based diagnosis would be useful for HIV-infected patients is a matter of debate, as is also the clinical significance of P. jirovecii colonization. The best alternative regimens for treating P. jirovecii pneumonia in cases of treatment failure or severe intolerance to trimethoprim-sulfamethoxazole are not clearly defined.. In the context of universal HIV testing and recent guideline recommendations to start antiretroviral therapy early in the course of HIV infection, the frequency of P. jirovecii pneumonia should continue to decline in France.

Topics: AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; France; HIV; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12 months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antitubercular Agents; Drug Resistance, Bacterial; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Meningeal

Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has long been recommended for immunosuppressed HIV-infected adults and children born to HIV-infected women. Despite this, many resource-limited countries have not implemented this recommendation, partly because of fear of widespread antimicrobial resistance not only to TMP-SMX, but also to other antibiotics. We aimed to determine whether TMP-SMX prophylaxis in HIV-infected and/or exposed individuals increases bacterial resistance to antibiotics other than TMP-SMX.. A literature search was conducted in Medline, Global Health, Embase, Web of Science, ELDIS, and ID21.. A total of 501 studies were identified, and 17 met the inclusion criteria. Only 8 studies were of high quality, of which only 2 had been specifically designed to answer this question. Studies were classified as (1) studies in which all participants were infected and/or colonized and in which rates of bacterial resistance were compared between those taking or not taking TMP-SMX and (2) studies comparing those who had a resistant infection with those who were not infected. Type 1 studies showed weak evidence that TMP-SMX protects against resistance. Type 2 studies provided more convincing evidence that TMP-SMX protects against infection.. There was some evidence that TMP-SMX prophylaxis protects against resistance to other antibiotics. However, more carefully designed studies are needed to answer the question conclusively.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Bacterial Infections; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; beta-Glucans; Biomarkers; Bronchoalveolar Lavage; Bronchoscopy; CD4 Lymphocyte Count; Dihydropteroate Synthase; Drug Resistance, Fungal; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumothorax; Polymerase Chain Reaction; Primary Prevention; Radiography, Thoracic; S-Adenosylmethionine; Secondary Prevention; Tetrahydrofolate Dehydrogenase; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Topics: Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Antitubercular Agents; Disease Outbreaks; Global Health; Government Programs; Health Facilities; Health Services Needs and Demand; HIV Infections; Humans; Infection Control; Isoniazid; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Diarrhoea is a major cause of morbidity and mortality among infants and children worldwide, especially in low- and middle-income countries. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a condition that similarly disproportionately affects low- and middle-income countries; of the nearly 2.1 million children under age 15 years living with HIV/AIDS, the large majority reside in sub-Saharan Africa. Infants and children with HIV infection have more frequent and more severe diarrhoea than children without HIV. Interventions including vitamin A, zinc and cotrimoxazole may contribute substantially to preventing diarrhoea in children with HIV infection or exposure to HIV.. We perform a systematic review of randomised controlled trials and nonrandomised studies that examine the effectiveness of vitamin A, zinc and cotrimoxazole on mortality and morbidity from diarrhoea in HIV-infected and -exposed infants and children.. Electronic databases including Pubmed, Central and EMBASE were searched without limits to language from 1980 to April 2010. Conference database searches were performed, experts were contacted and bibliographies were handsearched.. Randomised controlled trials (RCTs) and nonrandomised studies (NRSs) that examined the effectiveness of the three interventions were included.. Two reviewers independently assessed citations for eligibility and double-extracted included studies. Assessment of bias of individual studies was performed independently by both reviewers. Only two summary estimates were performed due to heterogeneity in study design and interventions.. Four RCTs were identified for vitamin A. One RCT was identified for zinc. One RCT and two NRSs were identified for cotrimoxazole. Vitamin A reduced mortality overall in children with HIV infection (four studies). A pooled estimate of three studies for reduction in mortality from vitamin A compared to placebo had a relative risk (DerSimonian and Laird method, random effects) of 0.50 (95% confidence interval (CI): 0.31 to 0.79) in 267 patients. Diarrheoa-specific mortality did not reach statistical significance and diarrhoeal morbidity outcomes were variable in three trials. Zinc supplementation reduced the number of physician visits for watery diarrhoea in one trial. Cotrimoxazole reduced mortality and hospitalisations compared to placebo in one RCT, although diarrhoea-specific morbidities were not significant.. Vitamin A shows benefits in reduction of mortality in HIV-infected children. The effect of vitamin A on children with HIV exposure is not clear and needs further review. Zinc and combination vitamin A, zinc and micronutrient supplementation did not show an effect compared to vitamin A alone in children with HIV infection. Cotrimoxazole reduced mortality and some morbidity in children with HIV infection. Further research may clarify the effects of these interventions on morbidity from diarrhoea and in the population of children with HIV exposure.

Topics: Anti-Infective Agents; Breast Feeding; Child; Diarrhea; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Micronutrients; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin A; Vitamins; Zinc

Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm(3), although the risks are much lower with use of highly active antiretroviral treatment.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis? What are the effects of antituberculosis prophylaxis in people with HIV infection? What are the effects of prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people with, and without, previous MAC disease? What are the effects of prophylaxis for cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV)? What are the effects of prophylaxis for invasive fungal disease in people with, and without, previous fungal disease? What are the effects of discontinuing prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir; antituberculosis prophylaxis; atovaquone; azithromycin (alone or plus rifabutin); clarithromycin (alone, or plus rifabutin and ethambutol); discontinuing prophylaxis for CMV, MAC, and PCP; ethambutol added to clarithromycin; famciclovir; fluconazole; isoniazid; itraconazole; oral ganciclovir; rifabutin (alone or plus macrolides); trimethoprim-sulfamethoxazole; and valaciclovir.

Topics: AIDS-Related Opportunistic Infections; Fluconazole; HIV Infections; Humans; Isoniazid; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) and tuberculosis (TB) are overlapping epidemics that cause an immense burden of disease in sub-Saharan Africa. This region is home to the majority of the world's co-infected patents, who have higher TB case fatality and recurrence rates than patients with TB alone. A World Health Organization interim policy has been developed to reduce the joint burden of TB-HIV disease, an important component of which is provision of HIV care to co-infected patients. This review focuses on HIV testing of TB patients and, for those who are HIV-positive, the administration of adjunctive cotrimoxazole preventive treatment (CPT) and antiretroviral treatment (ART). HIV testing has moved from a voluntary, client-initiated intervention to one that is provider-initiated and a routine part of the diagnostic work-up. The efficacy and safety of CPT in HIV-infected patients is now well established, and this is an essential part of the package of HIV care. ART scale-up in Africa can substantially improve outcomes in co-infected patients. However, the clinical and programmatic challenges of combining ART with anti-tuberculosis treatment need to be resolved to realise the full potential of this benefit. These include the optimal time to start ART, how best to combine rifampicin-containing regimens with first-line and second-line ART regimens, management of immune reconstitution disease, the role of isoniazid preventive treatment with ART after TB treatment completion, and where and how to provide combined treatment to best suit the patient. Clinical and operational studies in the next few years should help to resolve some of these issues.

Topics: Africa South of the Sahara; Anti-Infective Agents; Anti-Retroviral Agents; Comorbidity; Counseling; Disease Management; Drug Administration Schedule; Drug Synergism; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Children with HIV are at increased risk of acquiring tuberculosis (TB), a common cause of acute and chronic respiratory disease and death in HIV-infected children living in areas where prevalence of the disease is high. Children infected with HIV and TB have worse outcomes than HIV-uninfected children who have TB; thus, preventing the infection and disease in HIV-infected children is potentially an important public health intervention. Isoniazid, an anti-tuberculosis medication, has been used effectively to prevent TB in HIV-uninfected children, but currently there are no guidelines on the use of TB preventive therapy in HIV-infected children.. To determine the impact of TB preventive therapy on TB-related incidence and death in HIV-infected children. We searched the Cochrane Controlled Trials Register (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed, EMBASE, and AIDSearch. In addition, we scanned reference lists, manually searched conference abstracts, and contacted content experts.. We included studies of HIV-infected children randomised to receive TB preventive therapy or placebo, or an alternative TB preventive regimen. Participants could have tuberculin skin test results that were positive or negative.. Two authors independently used the study selection criteria, assessed methodological quality and extracted data. Effects were assessed using hazard ratios.. One trial met the selection criteria for the review. The trial participants were HIV-infected children, most of whom were not taking antiretroviral therapy. Subjects were randomised to isoniazid and cotrimoxazole or placebo and cotrimoxazole, given daily or three times a week. The trial showed a marked reduction in TB incidence and death in the isoniazid group. As yet, however, there are no long-term follow-up data on the durability of the protective effect or on possible long-term adverse events. This trial also was unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy.. Isoniazid prophylaxis in HIV-infected children has the potential to play a major public health role by reducing TB incidence and death. As yet, however, data are insufficient to guide the duration of prophylaxis and to support its use in children using highly active antiretroviral therapy (HAART) and in those living in areas of low TB prevalence. Further studies are needed to assess whether TB preventive therapy is of benefit in all HIV-infected children, irrespective of use of antiretroviral treatment, the optimal duration of preventive therapy, or long-term adverse events.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Child; HIV Infections; Humans; Incidence; Isoniazid; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus neoformans; HIV Infections; Humans; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic treatment. Without treatment, PCP is likely to be fatal in people with AIDS, so placebo-controlled studies would be considered unethical.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of adjuvant corticosteroids in people receiving first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of treatments for Pneumocystis pneumonia in people infected with HIV who have not responded to first-line antipneumocystis treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant corticosteroids, aerosolised or intravenous pentamidine, atovaquone, clindamycin-primaquone, treatment after failure of first-line treatment, trimethoprim-dapsone, and trimethoprim-sulfamethoxazole (TMP-SMX, co-trimoxazole).

Topics: Administration, Oral; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Atovaquone; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the prognostic value of selected laboratory and growth markers on the short-term risk of mortality in untreated HIV-infected children in resource-limited settings.. A meta-analysis of individual longitudinal data on children aged 12 months onwards from 10 studies (nine African, one Brazilian in the 3Cs4kids collaboration).. The risk of death within 12 months based on age and the most recent measurements of laboratory and growth markers was estimated using Poisson regression models, adjusted for cotrimoxazole prophylaxis use and study effects.. A total of 2510 children contributed 357 deaths during 3769 child-years-at-risk, with 81% follow-up occurring after start of cotrimoxazole. At first measurement, median age was 4.0 years (interquartile range, 2.2-7.0 years), median CD4% was 15% and weight-for-age z-score -1.9. CD4% and CD4 cell count were the strongest predictors of mortality, followed by weight-for-age and haemoglobin. After adjusting for these markers, the effects of total lymphocyte count and BMI-for-age were relatively small. Young children who were both severely malnourished and anaemic had high mortality regardless of CD4 values, particularly those aged 1-2 years. By contrast, high CD4% or CD4 cell count values predicted low mortality level amongst either children older than 5 years or those younger with neither severe malnutrition nor anaemia.. CD4 measurements are the most important indicator of mortality and wider access to affordable tests is needed in resource-limited settings. Evaluation of antiretroviral initiation in children also needs to consider weight-for-age and haemoglobin. Prevention and treatment of malnutrition and anaemia is integral to HIV paediatric care and could improve survival.

Topics: Africa; Anemia; Anti-Retroviral Agents; Biomarkers; Brazil; CD4 Lymphocyte Count; Child; Child Mortality; Child, Preschool; Hemoglobins; HIV; HIV Infections; Humans; Malnutrition; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

Drug hypersensitivity has been reported to occur 100 times more commonly in those living with HIV. In the first decade of HIV treatment, this mainly involved drugs used to treat HIV-related infections but now primarily includes drugs used to treat HIV. This review focuses on the current knowledge of the epidemiology, pathophysiology and clinical features of drug hypersensitivity reactions of drugs used in the management of the HIV-infected patient.. Our understanding of the immunogenetics and host predisposition to drug hypersensitivity has been advanced considerably by the antiretroviral drugs abacavir and nevirapine. The association of abacavir hypersensitivity reaction with HLA-B*5701 has been particularly important and provides a basis for genetic screening in the clinic setting.. The increased predisposition of drug hypersensitivity disease in HIV will continue to provide a fertile ground for study of the diverse and complex processes that drive its pathophysiology. Our knowledge of drug hypersensitivity will also increase as the expanding armentarium of antiretroviral therapy is applied to more diverse populations in the developing world. The potential for widespread implementation of HLA-B*5701 screening for abacavir hypersensitivity will set an important precedent for bringing individualized medicine to the clinic and the use of genetic testing to improve drug safety.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Dideoxynucleosides; Drug Hypersensitivity; Genetic Predisposition to Disease; HIV Infections; HLA-B Antigens; Humans; Reverse Transcriptase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination

The vicious interaction between the human immunodeficiency virus (HIV) infection and tuberculosis (TB) pandemics poses special challenges to national control programs and individual physicians. Although recommendations for the treatment of TB in HIV-infected patients do not significantly differ from those for HIV-uninfected patients, the appropriate management of HIV-associated TB is complicated by health system issues, diagnostic difficulties, adherence concerns, overlapping adverse-effect profiles and drug interactions, and the occurrence of paradoxical reactions after the initiation of effective antiretroviral therapy. In this article, recommended treatment strategies and novel approaches to the management of HIV-associated TB are reviewed, including adjuvant treatment and options for treatment simplification. A focused research agenda is proposed in the context of the limitations of the current knowledge framework.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Biomedical Research; Clinical Trials as Topic; Drug Administration Schedule; HIV; HIV Infections; Humans; Immunologic Factors; Micronutrients; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Bacterial infection is a major cause of morbidity and mortality among patients with HIV living in Africa. Broadening the scope of cotrimoxazole (CTX) prophylaxis to cover patients whose CD4 counts are above 200 cells/mm(3) has been suggested as a means of improving the control of infectious disease on the continent. CTX has demonstrated antimalarial benefit in Central and West Africa, but in areas of high bacterial resistance to CTX, the prophylactic role of CTX as an antibacterial agent is less clear. In particular there is little to suggest that prophylactic CTX provides reliable control against the pneumococcus. In both South Africa and the Gambia, several clinical studies with pneumococcal conjugate vaccines have resulted in improved clinical outcomes for children with and without HIV infection. There is clearly much more that needs to be done, and conjugate vaccines provide a unique opportunity to improve the future lives of Africa's children.

Topics: Adolescent; Adult; Africa South of the Sahara; Anti-Infective Agents; Bacterial Infections; Child; HIV Infections; Humans; Infant, Newborn; Pneumococcal Vaccines; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefit that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resource-limited settings. Despite co-trimoxazole's known clinical benefits, the potential operational benefits, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries--particularly sub-Saharan Africa--has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specific actions required to tackle these challenges.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Child; Child, Preschool; Developing Countries; Health Policy; HIV Infections; Humans; Infant; Infant, Newborn; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of dual Mycobacterium tuberculosis (TB) and Pneumocystis jiroveci (carinii) (PCP) lymphadenitis in a patient with HIV who had been receiving trimethoprim-sulfamethoxazole (TMP-SMX) as systemic prophylaxis for PCP. This patient was successfully treated with antituberculosis medications and TMP-SMX. Our review of the literature identified this as the first reported case of dual TB and PCP lymphadenitis in an HIV-infected host and highlights the potential limitations of TMP-SMX prophylaxis.

Topics: Adult; Antibiotic Prophylaxis; Female; HIV Infections; Humans; Lymphadenitis; Mycobacterium tuberculosis; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Lymph Node

Topics: Anti-Infective Agents; Antiprotozoal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV)/acquired immunedeficiency syndrome (AIDS) and tuberculosis (TB) cause an immense burden of disease in sub-Saharan Africa. A large amount of knowledge has been gathered in the last 15 years about the negative impact that HIV has on TB control, both at a programme level and at the level of the individual patient. Equally, interventions that are known to benefit patients have been tested and piloted, and these form important components of international TB-HIV guidelines, a TB-HIV strategic framework and an interim policy on TB-HIV coordination. Unfortunately, in sub-Saharan Africa there is little evidence that these interventions are being implemented on the ground, and one of the reasons for this paralysis is that the operational details are not well developed. This paper takes the three important HIV interventions of HIV testing and counselling, cotrimoxazole preventive treatment and antiretroviral treatment, and discusses some of the practical details of on-the-ground implementation. We hope that this will generate discussion, but above all, the impetus to start delivering services to patients.

Topics: Africa South of the Sahara; Antiviral Agents; HIV; HIV Infections; Humans; Infection Control; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Atovaquone; Clindamycin; Corticosterone; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

We examined the peer-reviewed literature on the burden of bacterial pneumonia and the effectiveness of interventions for its prevention among HIV-infected adults in developed and developing countries. Bacterial pneumonia rates were up to 25-fold higher among HIV-infected adults than in the general community, with rates increasing as CD4+ T-cell count decreases. In developed countries, cohort studies showed that highly active antiretroviral therapy (HAART) had the most consistent effect on reducing pneumonia. In a prospective cohort and case-control studies from these regions, pneumococcal polysaccharide vaccine reduced pneumococcal disease in certain subgroups, particularly those with higher CD4+ T cells/microL. In patients with fewer than 200 CD4+ T cells/microL, antimicrobial prophylaxis was usually effective in reducing pneumonia. In sub-Saharan Africa, randomised controlled trials concluded that co-trimoxazole prophylaxis decreased rates of bacterial pneumonia, but pneumococcal polysaccharide vaccine prevented neither pneumonia nor invasive pneumococcal disease. Although not yet fully evaluated in Africa, based on experience in industrialised nations, use of HAART in Africa may have substantial potential to prevent bacterial pneumonia.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clinical Trials as Topic; HIV Infections; Humans; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Drug hypersensitivity is a major problem in HIV medicine. These reactions limit the choice of antiretrovirals that can be used in a patient and, at times, can lead to failure to administer an adequate regimen. Hypersensitivity reactions occur in a minority of patients, but represent a high cost both to the patient and to health services. Our current understanding of these reactions is based on the hapten and the danger hypotheses, which state that a drug signal by itself is insufficient to induce an immune response but must be accompanied by co-stimulatory or danger signals. Furthermore, individual susceptibility to a hypersensitivity reaction may be determined by genetic factors. In this review, we explore our understanding of the immunological mechanisms of hypersensitivity to drugs used in HIV-positive patients, by using sulphamethoxazole and abacavir as paradigms. A deeper understanding of the mechanism(s) of these reactions will help us in their prevention, diagnosis and treatment.

Topics: Anti-Bacterial Agents; Dideoxynucleosides; Drug Hypersensitivity; Female; HIV Infections; HIV-1; Humans; Male; Reverse Transcriptase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination

The prevention and early treatment of infections are the mainstay of the medical management of the majority of people with HIV infection, who live in low income countries without access to antiretroviral drugs. Cotrimoxazole is cheap and effective against a wide range of organisms. However, routine prophylactic treatment is difficult to deliver in low-resource settings, and could also lead to increased resistance to the drug.. To assess the effects of routinely administered cotrimoxazole on death and illness episodes in HIV infected adults.. We searched the Cochrane HIV/AIDS Group register, the Cochrane Controlled Trials Register, MEDLINE, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and tuberculosis (TB) conferences (search date July 2001). We checked reference lists for trials and other pertinent articles, and contacted pharmaceutical companies and experts in the field.. Randomised or quasi randomised trials comparing routinely administered cotrimoxazole versus placebo or no treatment in adults (age greater than 13 years).. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear trial authors were contacted for further details.. Four trials involving 1476 people were identified. Three trials (1416 people) studied heterosexual men and women in West Africa. A fourth trial was of homosexual men on chemotherapy for Kaposi's sarcoma, in the United States. Meta-analysis of the three African trials showed a significant beneficial effect of cotrimoxazole for death: relative risk 0.69 (95% confidence interval 0.55 to 0.87); for morbid events: 0.76 (0.64 to 0.9); and for hospitalisation: 0.66 (0.48 to 0.92). There was no significantly greater risk of adverse effects: relative risk 1.28 (0.47 to 3.51). Effects were similar in people with early and advanced HIV disease. Insufficient evidence was found on effects in areas with higher bacterial resistance or in people on antiretroviral therapy.. In the trials included in the review, cotrimoxazole prophylaxis had a beneficial effect in preventing death and illness episodes in adults with both early and advanced HIV disease. However, the wider applicability of these findings is unclear, in particular to areas with higher background bacterial resistance to cotrimoxazole. Further trials would be required in differing settings to widen applicability.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Infections; Humans; Male; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Africa South of the Sahara; Anti-Infective Agents; HIV Infections; Humans; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Topics: Aortic Valve Insufficiency; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Gram-Negative Bacterial Infections; HIV Infections; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mouth; Ofloxacin; Rheumatic Heart Disease; Risk Factors; Stenotrophomonas maltophilia; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is still the commonest AIDS-defining condition in the UK, although absolute numbers have fallen since 1990 with the advent of prophylaxis and highly active antiretroviral therapy (HAART). Further decreases in its incidence are unlikely unless efforts are made to reduce late first presentations of HIV, improve retention of patients in care and improve adherence to P. carinii prophylaxis. The widespread development of key mutations in the P. carinii dihydropteroate synthase gene in the 1990's suggests that the organism is evolving under positive evolutionary pressure, possibly mediated by widespread use of co-trimoxazole and dapsone prophylaxis. It is not clear whether these mutants lead to treatment failure with co-trimoxazole, since most episodes are treated successfully and failure of prophylaxis is rare. Molecular diagnosis of PCP is restricted to research use, due to difficulties with sensitivity, specificity and turn-around times. Patients are infected with multiple P. carinii subtypes and re-infection from an environmental source is probably more important than re-activation of an existing infection. Person-to-person transmission does not appear to be a major source of infection in HIV-infected patients. Recent reports have highlighted the potential complications of initiating HAART during treatment of PCP.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Fungal; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Child; Child, Preschool; HIV Infections; Humans; Infant; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Two recent placebo-controlled trials of cotrimoxazole in HIV-infected adults, conducted by independent groups but in the same city (Abidjan, Côte d'Ivoire), have both shown important positive impacts. One study where cotrimoxazole or placebo was given to tuberculosis-HIV co-infected patients showed a significant reduction in mortality; the second study with a similar protocol, in HIV-infected patients without major co-morbidity at trial entry, showed a significant reduction in morbidity but no effect on mortality. These data have been interpreted by some as conclusive enough to recommend cotrimoxazole for all people with HIV/AIDS in Africa. Others have been more cautious, noting that Abidjan has an atypically low rate of cotrimoxazole resistance among bacterial pathogens, and consider more data are needed before such a sweeping policy decision can be made. Recent data from Senegal showed no benefit but this trial, like several others, was terminated prematurely because the investigators felt it unethical to continue after the Abidjan results were released. The situation is somewhat confused and confusing. This review attempts to put the current debate into context and to review the current position of cotrimoxazole in relation to other primary prophylaxis strategies in Africa.

Topics: Adult; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Resistance, Bacterial; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Antitubercular Agents; CD4 Lymphocyte Count; Chemoprevention; Drug Interactions; Ganciclovir; HIV Infections; Humans; Practice Guidelines as Topic; Secondary Prevention; Trimethoprim, Sulfamethoxazole Drug Combination

Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge.

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Hydroxylamines; Male; Pneumonia; Sulfanilamides; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

The incremental administration of trimethoprim-sulfamethoxazole (i.e., desensitization) in previously hypersensitive HIV-infected patients has been evaluated to date in 7 studies involving more than 10 patients. These studies differ greatly from one to another according to the inclusion criteria, exclusion criteria, and desensitization procedure (duration, lagtime between 2 doses). The efficacy varies from 33% to 100% but one can expect success in 3 out of 4 patients whatever the duration of the desensitization procedure. Short procedures seem better than long ones from the compliance point of view. These different procedures have not been compared each other. The reputation of good tolerance of this procedure is challenged by the recent description of severe life-threatening systemic reaction. Subsequent contra-indications must be ruled out and this procedure must be supervised in hospital.

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

Topics: Administration, Inhalation; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Dapsone; Encephalitis; HIV Infections; Humans; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Randomized Controlled Trials as Topic; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Despite a large amount of research of periodontal health seen in HIV infection, much remains to be learned. Very few large controlled studies of infected people at settings not self-selected for oral disease have been reported, and few have investigated the necrotising periodontal diseases described in HIV infection. In this paper we present a brief review of three approaches to identify periodontal changes associated with HIV infection and identify possible aetiological factors for them. First, we summarise the methods and findings of a controlled blinded study of the periodontal health of homosexual men attending a genito-urinary medicine clinic. Second, we precis a case-control study of gingival ulceration among patients at a dedicated dental clinic. Finally, we outline how the validity of diagnostic criteria for HIV-associated periodontal changes were tested against the data collected in the controlled study.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Candidiasis, Oral; Case-Control Studies; CD4 Lymphocyte Count; Gingival Diseases; Gingivitis, Necrotizing Ulcerative; HIV Infections; Humans; Male; Oral Ulcer; Periodontal Diseases; Prognosis; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination

It is postulated that the unstable hydroxylamine metabolite of sulphamethoxazole is responsible for the adverse reactions to co-trimoxazole and in HIV infection systemic glutathione deficiency leads to a reduced capacity to counteract the hydroxylamine toxicity. This hypothesis has been investigated by studying the metabolism of sulphamethoxazole and assessing glutathione status in HIV infection in order to explore the modification of treatment. It is concluded that the toxicity of plasma sulphamethoxazole hydroxylamine is counteracted by normal glutathione concentrations as is the case in HIV-seropositive patients, but that increased oxidation within certain cells in HIV infected individuals may possibly give rise to increased concentrations of reactive intermediates of sulphamethoxazole. Sulphametrole and sulphamethoxazole have similar half-lives but are metabolized differently: in vivo no oxidised metabolites of sulphametrole could be detected. In a retrospective study the rate of adverse reactions to trimethoprim-sulphametrole appeared to be in the lower range of those reported for trimethoprim-sulphamethoxazole indicating that the combination of trimethoprim-sulphametrole may be more favourable. The ratio of trimethoprim:sulphonamide is 1:5, but in-vitro studies with Toxoplasma gondii indicate that because of the synergic effect of both agents the dose of sulphonamide is possibly unnecessarily high.

Topics: Anti-Infective Agents; Glutathione; HIV Infections; Humans; Hydroxylamines; Trimethoprim, Sulfamethoxazole Drug Combination

Although alternative therapy for PCP remains limited, the role of TMP/SMX desensitization becomes increasingly important in patients with AIDS. Various successful desensitization protocols have been described in this article. As there are no established guidelines, it appears that the desensitization procedure can occur in small successive doses given each day or one small dose given daily. An evaluation of the severity of allergic reaction can be used to determine the type of dosing regimen. We believe that protocols starting with low doses and slow titration to full-dose therapy, as used at our institution, should be efficacious. Monitoring of the patient after the desensitization procedure should continue, as sensitivity may reoccur. In addition, while the patient is undergoing desensitization, some investigators recommend that alternative therapy be continued until full-dose TMP/SMX therapy is achieved. Also, it is important to realize that once a patient is successfully desensitized, medication compliance must be maintained because, theoretically, reexposure to the drug after a lapse in therapy may result in hypersensitivity reactions. Therefore, this procedure and the possibility of serious adverse effects, such as Stevens-Johnson syndrome and anaphylaxis, should be evaluated carefully and discussed thoroughly with each patient prior to initiation of therapy. Finally, a study of sufficient size should be performed to evaluate the efficacy of desensitization regimens and establish specific dosing guidelines.

Topics: Anti-Infective Agents; Desensitization, Immunologic; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The transmission, diagnosis, and clinical manifestations of human immunodeficiency virus (HIV) infection in children up to 13 years of age are reviewed, and maintenance and prophylactic drug therapies for these patients are discussed. HIV can be transmitted from mother to infant in utero, during delivery, or through breast milk. Perinatal transmission accounts for almost 90% of all pediatric HIV infections. HIV infection can be diagnosed with HIV culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing should begin as soon as possible after the at-risk child reaches one month of age. CD4+ lymphocyte counts are also used in diagnosis and monitoring. The median age at diagnosis of AIDS in children with perinatally acquired HIV infection is 12-24 months. Among the many possible clinical features are Pneumocystis carinii pneumonia (PCP), cytomegalovirus infection, failure to thrive, encephalopathy, recurrent bacterial infection, thrush, lymphoid interstitial pneumonitis, lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia. Zidovudine is considered the drug of choice for initial therapy in HIV-infected children and is indicated for asymptomatic infection, early symptomatic disease, and advanced disease. However, new research is questioning the role of zidovudine monotherapy. Didanosine is the only agent with FDA-approved labeling for use as second-line therapy in children who do not respond to or become resistant to zidovudine. Agents under investigation for pediatric use are zalcitabine, stavudine, lamivudine, and nevirapine. Drug combinations, such as zidovudine plus didanosine, are also being examined. Zidovudine appears to reduce the rate of maternal transmission of HIV. Agents used prophylactically against PCP in children are trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v. pentamidine. HIV-infected children should also received prophylaxis against recurrent bacterial infections. The standard pediatric immunization schedule is used, but inactivated injectable poliovirus vaccine must be given instead of the live oral vaccine. Zidovudine remains the first-line agent for treating HIV infection in children. Alternatives are available for those who do not respond to zidovudine.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Dapsone; Didanosine; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine; Zidovudine

Several recent reports have described an association between human immunodeficiency virus (HIV) infection and porphyria cutanea tarda (PCT). We describe two HIV-infected patients who developed PCT and review 29 other reported cases of coexistent PCT and infection due to HIV. Recognized porphyrinogenic factors were identified in our patients and in 27 of the 29 cases described in the literature. Even in the two cases that lacked obvious precipitant factors for PCT, the possibility of hepatitis C was not excluded. This fact suggests that the co-occurrence of PCT and infection due to HIV may reflect the coexistence of risk factors for the two diseases rather than a causal association. Despite concern that exposure to sulfonamides might exacerbate porphyria, one of our patients and three patients described in the literature were safely treated with sulfonamides.

Topics: Adult; HIV Infections; HIV-1; Humans; Male; Porphyria Cutanea Tarda; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytomegalovirus Retinitis; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The pancreas is frequently involved during HIV infection, especially by disseminated infections or neoplasms. These lesions are generally asymptomatic and are discovered at autopsy. However, hypoglycaemia secondary to massive pancreatic infiltration by a tumour or tuberculous necrosis may occur. The most important cause of pancreatic dysfunction in HIV-infected patients is a drug toxic effect (intravenous pentamidine, didanosine, zalcitabine). Hypoglycaemia, which may or may not be followed by diabetes, can develop during intravenous pentamidine therapy. In cases with increased serum amylase and/or lipase levels, potentially toxic drugs must be promptly discontinued to avoid major pancreatic involvement.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Didanosine; HIV Infections; Humans; Pancreas; Pancreatic Diseases; Pancreatitis; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine

Human immunodeficiency virus-infected patients are exposed to more or less specific iatrogenic diseases. The main characteristics of the risks encountered in this field are described: drug intolerance, mostly to sulfamethoxazole-trimethoprim, is extremely frequent; nucleoside analogue antiviral toxicity is reminiscent of that of chemotherapy; nosocomial infections, in general, are more prominent than in HIV-non infected patients. Intravenous line infections are particularly frequent, but these devices are necessary for prolonged intravenous therapies such as anti-CMV treatment of parenteral nutrition. An improved understanding of different etiopathogenic mechanisms and a better approach of the toxicity/efficacy ratio for each treatment would allow to reduce the excessive morbidity due to iatrogenicity.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; CD4-CD8 Ratio; Cross Infection; HIV Infections; Humans; Iatrogenic Disease; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is an important medication for the treatment and prevention of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Use of this medication has been limited by the high frequency of adverse reactions that occur in patients with human immunodeficiency virus disease. This article reviews the incidence and spectrum of adverse reactions and options for continuing therapy with trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients who have adverse reactions.

Topics: AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Drug Eruptions; HIV Infections; Humans; Pneumonia, Pneumocystis; Sulfanilamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Clinical Trials as Topic; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Following the initial observation by Dr. Margaret Fischl that trimethoprim-sulfamethoxazole can prevent Pneumocystis carinii infection in patients with Kaposi's sarcoma, initiating prophylaxis for pneumocystic infection in all patients with less than 200 CD4+ cells/mm3 has become accepted practice. This prophylactic intervention has been found not only to reduce the development of pneumonia due to P. carinii but also to prolong life. Drs. Henry Masur and Joseph A. Kovacs first reviewed prophylaxis for P. carinii pneumonia in patients infected with the human immunodeficiency virus for the AIDS Commentary 3 years ago. They have updated that initial review for this AIDS Commentary, placing currently available information into concise clinical perspective and detailing a rational plan for the clinician to follow based on results of recent studies.

Topics: Administration, Inhalation; Aerosols; CD4-Positive T-Lymphocytes; HIV Infections; Humans; Leukocyte Count; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The clinical features of three patients with a life-threatening reaction to trimethoprim-sulfamethoxazole (TMP-SMZ) are presented along with seven other cases from the literature. All patients developed sudden fever and hypotension immediately after the administration of TMP-SMZ; usually this reaction occurred within approximately 2 weeks of completion of a previous course of the drug. All but one patient had a rash. Most patients were hypoxemic and developed diffuse pulmonary infiltrates. All patients responded rapidly to supportive care, while bacterial cultures remained negative. The presence, absence, or character of previous adverse reactions to TMP-SMZ did not predict subsequent severe reactions. Although its mechanism remains unclear, this reaction has features of both IgE-mediated anaphylaxis and cytokine (tumor necrosis factor)-mediated effects. We advise extreme caution, with close observation, when this drug is first readministered to patients who have experienced any TMP-SMZ-associated toxicity within the previous 6-8 weeks.

Topics: Adult; Diarrhea; Dyspnea; Fever; HIV Infections; Humans; Hypotension; Hypoxia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The diagnosis of Pneumocystis carinii pneumonia (PCP) rests on the isolation of this micro-organism in patients whose latest blood count, less than 2 months old, shows less than 250 CD4 lymphocytes per cubic mm and who present with signs of impaired lung function. Bronchoalveolar lavage (BAL) is the reference diagnostic method, but induced expectoration may be the initial examination, in which case BAL is performed only when the latter fails or gives negative results. Prognostic factors are those of any interstitial pneumonia plus those specific to PCP and those associated with HIV infection. It is only when no initial severity factor is present that cure can be contemplated, provided the effectiveness of treatment is evaluated daily. Cotrimoxazole is the reference drug for comparisons with all new treatments; the indications of corticosteroid therapy and the necessity of intensive care techniques are now better determined. The frequency of PCP and its mortality rate should be reduced, and one may look forward to a time when this disease will be rare and atypical, thereby raising other diagnostic and therapeutic problems.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; CD4-Positive T-Lymphocytes; Dapsone; Eflornithine; Folic Acid Antagonists; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Quinazolines; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Although Pneumocystis carinii pneumonia (PCP) can occur in any patient with severe impairment of immunity, there has been a sharp rise in incidence with the spread of human immunodeficiency virus through the USA and Western Europe, where nearly 80% of patients with HIV infection have at least one episode of PCP during their lifetime (Murray et al, 1984).

Topics: Antimalarials; CD4-Positive T-Lymphocytes; Clinical Protocols; Dapsone; Drug Combinations; HIV Infections; HIV-1; Humans; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Female; HIV Infections; Humans; Infant; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

At the end of the first consensus conference on anti-infectious therapy organized by the French Language Society of Infectious Pathology in May 1990 and devoted to pneumocystosis in patients with human immunodeficiency virus (HIV) infection, the consensus committee produced this paper which answers the following 4 questions: what are the indications, technical requirements, sensitivity and benefits of induced expectoration in the diagnosis of Pneumocystis carinii pneumonia? what are the initial and secondary severity factors; in which cases is transfer to an intensive care unit indicated; in which manner can treatment be modified? what is the position occupied by corticosteroid therapy in the management of pneumocystosis? when is prophylaxis of pneumocystosis indicated; what prophylactic methods are used and how to choose among them?

Topics: Acquired Immunodeficiency Syndrome; Aerosols; Clinical Protocols; Dapsone; France; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Product Surveillance, Postmarketing; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Bacterial Infections; HIV Infections; HIV-1; Humans; Mycoses; Opportunistic Infections; Pentamidine; Protozoan Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

Topics: Adrenal Cortex Hormones; Dapsone; France; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Resuscitation; Trimethoprim, Sulfamethoxazole Drug Combination

We investigated the impact of prolonged cotrimoxazole prophylaxis on growth in 2848 HIV-exposed uninfected children enrolled in the Mpepu study, a randomized, placebo-controlled trial in Botswana. No significant differences in mean weight-for-age, length-for-age, or weight-for-length z scores between placebo and cotrimoxazole arms were observed overall through 18 months.

Topics: Botswana; Child; HIV Infections; Humans; Infant; Trimethoprim, Sulfamethoxazole Drug Combination

Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART.. We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 +  cells/μl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ).. We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4-12 weeks). CD4 + cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558.. Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4 + cell count or viral load.. In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.

Topics: Adult; Antimalarials; CD4 Lymphocyte Count; Chemoprevention; HIV Infections; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00-1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96-1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs.

Topics: Adult; Antitubercular Agents; Chloroquine; Cohort Studies; HIV Infections; Humans; Isoniazid; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021.. Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable.. From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9-4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64-8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14-78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21-6.45)] were significant predictors of mortality.. In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals.

Topics: CD4 Lymphocyte Count; Child; Child, Preschool; Coinfection; Ethiopia; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Infant; Male; Mycobacterium tuberculosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.. We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population.. 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001).. Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa. Clinical Trials Registration. NCT01650558.

Topics: Adult; Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Malawi; Trimethoprim, Sulfamethoxazole Drug Combination

The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than sulphadoxine-pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary end point) among HIV-positive pregnant women with a CD4+ count ≥350 cells/mm. MACOMBA is a multicentre, open-label randomised trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomised and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitaemia or PCR.. Thirteen women had a placental infection: five in the CTX arm (one by microscopic placental parasitaemia and four by PCR) and eight by PCR in the SP-IPTp (8.5% vs. 15.1%, p = 0.28). The percentage of newborns with low birthweight (<2500 g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms.. Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO.

Topics: Adult; Antimalarials; Central African Republic; Drug Combinations; Female; HIV Infections; Humans; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cotrimoxazole preventive therapy (CPT) in human immunodeficiency virus (HIV) infection is a World Health Organization-recommended standard of care in resource-limited settings, but the mechanism of CPT's beneficial effects is unclear. The COSTOP trial (ISRCTN44723643) evaluated the noninferiority of discontinuing CPT in stabilized patients on antiretroviral therapy. The COSTOP immunology substudy was conducted on a subset of COSTOP participants randomized to continue CPT (n = 86) or discontinue CPT (placebo, n = 86) as daily treatment for 1 year.. We evaluated whether CPT reduces microbial translocation, indicated by the presence of bacterial lipopolysaccharide (LPS) and LPS control factors such as soluble CD14 (sCD14) and endotoxin core antibody (EndoCAb immunoglobulin M [IgM]) in plasma. Intestinal barrier damage as indicated by plasma intestinal fatty acid binding protein (IFABP), T-cell activation, and the inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were also evaluated.. We found no significant change in markers of microbial translocation (LPS, IFABP, sCD14, and T-cell activation), with decreased EndoCAb IgM. There was significant increase in inflammation markers (CRP and IL-6) after stopping CPT compared to those who continued CPT.. These results add to the evidence of immunological benefits of CPT among HIV-infected populations in resource-limited settings. However, no evidence of reducing microbial translocation was observed.

Topics: Adult; Anti-HIV Agents; Biomarkers; C-Reactive Protein; CD4 Lymphocyte Count; Double-Blind Method; Female; HIV Infections; Humans; Immunoglobulin M; Inflammation; Interleukin-6; Linear Models; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment

An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/μL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis.. This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period.. We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis.. This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; China; Clindamycin; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfamethoxazole; Sulfonamides; T-Lymphocytopenia, Idiopathic CD4-Positive; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin B Complex

Cotrimoxazole (CTX) is a broad-spectrum antimicrobial, combining trimethoprim and sulfamethoxazole. CTX prophylaxis reduces mortality and morbidity among people living with HIV in regions with high prevalence of bacterial infections and malaria. The Antiretroviral research for Watoto trial evaluated the effect of stopping versus continuing CTX prophylaxis in sub-Saharan Africa.. In this study, 72 HIV-infected Zimbabwean children, on antiretroviral therapy, provided fecal samples at 84 and 96 weeks after randomization to continue or stop CTX. DNA was extracted for whole metagenome shotgun sequencing, with sequencing reads mapped to the Comprehensive Antibiotic Resistance Database to identify CTX and other antimicrobial resistance genes.. There were minimal differences in the carriage of CTX resistance genes between groups. The dfrA1 gene, conferring trimethoprim resistance, was significantly higher in the continue group (P = 0.039) and the tetA(P) gene conferring resistance to tetracycline was significantly higher in the stop group (P = 0.013). CTX prophylaxis has a role in shaping the resistome; however, stopping prophylaxis does not decrease resistance gene abundance.. No differences were observed in resistance gene carriage between the stop and continue groups. The previously shown multi-faceted protective effects of CTX in antiretroviral research for Watoto trial clinical outcomes are not outweighed by the risk of multi-drug resistance gene selection due to prophylaxis. These findings are reassuring, given current recommendations for long-term CTX prophylaxis among children living with HIV in sub-Saharan Africa to decrease mortality and morbidity.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Child; Child, Preschool; Drug Resistance, Microbial; Female; Gastrointestinal Microbiome; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Zimbabwe

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Brain; Brazil; Female; HIV Infections; Humans; Male; Middle Aged; Neuroimaging; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

WHO guidelines recommend co-trimoxazole prophylaxis for HIV-exposed, HIV-uninfected infants. These guidelines date back to an era in which HIV testing of infants was impossible and mothers had poor access to antiretroviral treatment. To determine whether this guideline requires revision in the current era of effective prevention of mother-to-child transmission and early infant diagnosis programmes, we aimed to investigate whether receiving no co-trimoxazole prophylaxis is inferior to receiving co-trimoxazole prophylaxis in the resulting incidence of grade 3 or 4 common childhood illnesses or mortality in breastfed HIV-exposed, HIV-uninfected infants.. We investigated our aim in a randomised controlled, non-inferiority trial. We enrolled the HIV-negative infants of mothers living with HIV who were actively involved in transmission prevention programmes in two clinics in Durban, South Africa. Infants were included in the study if they were breastfeeding at the screening and enrolment visits, and their mother was planning to breastfeed for at least 6 months; were a singleton birth and had a birthweight of 2 kg or more; had no clinically observed genetic disorders; and had no serious illnesses and had not received antibiotics or traditional medications (such as herbal remedies). Infants were randomly assigned (1:1) to receive co-trimoxazole or no co-trimoxazole. In the co-trimoxazole group, infants received the drug until all exposure to HIV had ceased (ie, 6 weeks after last exposure to breastmilk) and the infant was confirmed to be uninfected with HIV. The drug was administered by mothers in once-daily regimens of 20 mg trimethoprim and 100 mg sulfamethoxazole orally (age <6 months or bodyweight <5 kg), or 40 mg trimethoprim and 200 mg sulfamethoxazole orally (age >6 months or bodyweight >5 kg). Clinical and laboratory staff always remained masked to group assignment, but mothers and study counsellors were not. Infants and their mothers attended study visits at ages 6 weeks (for enrolment and randomisation), 10 weeks, 14 weeks, and then monthly from 4 to 12 months. Our primary outcome was the incidence of grade 3 or 4 common childhood illnesses (pneumonia or diarrhoea) or mortality in breastfed HIV-exposed, HIV-uninfected infants by age 12 months. A non-inferiority bound of 5% was used. The study is registered with the Pan African Clinical Trials Registry, number PACTR201311000621110, and the South African National Clinical Trials Registry, number DOH-27-0614-4728.. We screened 1570 mother-child pairs for study enrolment, from whom (78%) eligible infants were enrolled into the study between Oct 16, 2013, and May 23, 2018. Of the infants enrolled, 611 (50%) were randomly assigned to the co-trimoxazole group and 609 (50%) were randomly assigned to the no co-trimoxazole group. One (<1%) infant in the no co-trimoxazole group was excluded from the analysis of the final outcomes for having received traditional medicine (which only became apparent after randomisation); therefore, 611 (50%) infants in the co-trimoxazole group and 608 (50%) infants in the no co-trimoxazole group were included in the final intention-to-treat analysis. 136 (22%) infants in the co-trimoxazole group and 139 (23%) infants in the no co-trimoxazole group did not complete the 12-month study visit, predominantly because of loss to follow-up (93 [15%] infants in the co-trimoxazole group; 90 [15%] infants in the no co-trimoxazole group). The cumulative probability of the composite primary outcome was 0·114 (95% CI 0·076 to 0·147; 49 events) in the co-trimoxazole group versus 0·0795 (0·044 to 0·115; 39 events) in the no co-trimoxazole group. The risk difference (no co-trimoxazole group minus co-trimoxazole group) was -0·0319 (-0·075 to 0·011), meaning that the risk was around 3 percentage points lower in the no co-trimoxazole group on the additive scale.. We can conclude that no co-trimoxazole is not inferior to daily co-trimoxazole among breastfed HIV-exposed, HIV-uninfected infants whose mothers are accessing a prevention of mother-to-child transmission programme in an area unaffected by malaria. We therefore believe that WHO should revise the co-trimoxazole guidelines for HIV-exposed, HIV-uninfected infants in areas unaffected by malaria.. HIV Prevention Research Unit of the South African Medical Research Council and the Family Larsson-Rosenquist Foundation.

Topics: Antibiotic Prophylaxis; Female; HIV Infections; Humans; Infant; Infant Mortality; Male; Morbidity; South Africa; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prevents opportunistic infections including falciparum malaria in HIV-infected individuals but there are concerns of cross-resistance to other antifolate drugs such as sulphadoxine-pyrimethamine (SP). In this study, we investigated the prevalence of antifolate-resistance mutations in Plasmodium falciparum that are associated with SP resistance in HIV-infected individuals on antiretroviral treatment randomized to discontinue (STOP-CTX), or continue (CTX) cotrimoxazole in Western Kenya.. Samples were obtained from an unblinded, non-inferiority randomized controlled trial where participants were recruited on a rolling basis for the first six months of the study, then followed-up for 12 months with samples collected at enrollment, quarterly, and during sick visits.. Plasmodium DNA was extracted from blood specimens. Initial screening to determine the presence of Plasmodium spp. was performed by quantitative reverse transcriptase real-time PCR, followed by genotyping for the presence of SP-resistance associated mutations by Sanger sequencing.. The prevalence of mutant haplotypes associated with SP-resistant parasites in pfdhfr (51I/59R/108N) and pfdhps (437G/540E) genes were significantly higher (P = 0.0006 and P = 0.027, respectively) in STOP-CTX compared to CTX arm. The prevalence of quintuple haplotype (51I/59R/108N/437G/540E) was 51.8% in STOP-CTX vs. 6.3% (P = 0.0007) in CTX arm. There was a steady increase in mutant haplotypes in both genes in STOP-CTX arm overtime through the study period, reaching statistical significance (P < 0.0001).. The frequencies of mutations in pfdhfr and pfdhps genes were higher in STOP-CTX arm compared to CTX arm, suggesting cotrimoxazole effectively controls and selects against SP-resistant parasites.. ClinicalTrials.gov NCT01425073.

Topics: Adolescent; Adult; Antimalarials; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Folic Acid Antagonists; Haplotypes; HIV Infections; Humans; Kenya; Malaria, Falciparum; Mutation; Plasmodium falciparum; Pre-Exposure Prophylaxis; Prevalence; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Long-term cotrimoxazole prophylaxis reduces mortality and morbidity in HIV infection, but the mechanisms underlying these clinical benefits are unclear. Here, we investigate the impact of cotrimoxazole on systemic inflammation, an independent driver of HIV mortality. In HIV-positive Ugandan and Zimbabwean children receiving antiretroviral therapy, we show that plasma inflammatory markers were lower after randomization to continue (

Topics: CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cytokines; Disease Progression; Epithelial Cells; Gastrointestinal Microbiome; HIV Infections; Humans; Inflammation; Inflammation Mediators; Intestines; Nutritional Status; Phenotype; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.

Topics: Adult; Anti-Retroviral Agents; Cohort Studies; Female; HIV; HIV Infections; Humans; Incidence; Infant, Newborn; Inflammation; Malaria; Pregnancy; Premature Birth; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

In sub-Saharan Africa, 20%-25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity.. Participants started ART with a CD4 count <100 cells/µL; enhanced prophylaxis comprised cotrimoxazole plus 12 weeks of isoniazid + fluconazole, single-dose albendazole, and 5 days of azithromycin. A blinded committee adjudicated events and causes of death as (non-mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infection (SBI), other potentially azithromycin-responsive infections, other events, and unknown.. Median pre-ART CD4 count was 37 cells/µL. Among 1805 participants, 225 (12.7%) died by week 48. Fatal/nonfatal events occurred early (median 4 weeks); rates then declined exponentially. One hundred fifty-four deaths had single and 71 had multiple causes, including tuberculosis in 4.5% participants, cryptococcosis in 1.1%, SBI in 1.9%, other potentially azithromycin-responsive infections in 1.3%, other events in 3.6%, and unknown in 5.0%. Enhanced prophylaxis reduced deaths from cryptococcosis and unknown causes (P < .05) but not tuberculosis, SBI, potentially azithromycin-responsive infections, or other causes (P > .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P < .05), but not SBI, other potentially azithromycin-responsive infections, or other events (P > .2).. Enhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease.. ISRCTN43622374.

Topics: Adolescent; Adult; Africa South of the Sahara; Aged; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Cryptococcosis; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Morbidity; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda.. COSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/μL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event.. 2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59-0.82; log-rank χ2 = 18.08; P<0.0001). 362 (276 PLC, 86 CTX) participants experienced at least one episode of confirmed clinical malaria (P<0.0001).. In ART stable patients with CD4 counts ≥250 cells/μL, continued CPT significantly reduces risk of severe bacterial infections and protects against malaria, while discontinuing CPT reduces haematological adverse events.

Topics: Adult; Anti-HIV Agents; Female; HIV Infections; Humans; Male; Middle Aged; Opportunistic Infections; Placebos; Safety; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment

Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide-treated nets remain the main interventions for prevention of malaria in human immunodeficiency virus (HIV)-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these interventions, and new ones are needed.. We conducted a double-blinded, randomized, placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide had recently been implemented. Participants were enrolled between gestation weeks 12 and 28 and given an insecticide-treated net. The primary outcome was detection of active or past placental malarial infection by histopathologic analysis. Secondary outcomes included incidence of malaria, parasite prevalence, and adverse birth outcomes.. All 200 women enrolled were followed through delivery, and the primary outcome was assessed in 194. There was no statistically significant difference in the risk of histopathologically detected placental malarial infection between the daily TMP-SMX plus DP arm and the daily TMP-SMX alone arm (6.1% vs. 3.1%; relative risk, 1.96; 95% confidence interval, .50-7.61; P = .50). Similarly, there were no differences in secondary outcomes.. Among HIV-infected pregnant women in the setting of indoor residual spraying of insecticide, adding monthly DP to daily TMP-SMX did not reduce the risk of placental or maternal malaria or improve birth outcomes.. NCT02282293.

Topics: Adult; Antimalarials; Artemisinins; Double-Blind Method; Endpoint Determination; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Pregnancy; Pregnancy Complications, Infectious; Quinolines; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear.. HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14-34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761.. From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference -0·2%, 95% CI -1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the co-trimoxazole group vs 17·4% in the placebo group, p=0·19) or grade 3-4 clinical adverse events (16·5% vs 18·4%, p=0·18). Grade 3-4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93), but grade 3-4 neutropenia was more frequent in the co-trimoxazole group than in the placebo group (8·1% vs 5·8%, p=0·03). More co-trimoxazole resistance in commensal Escherichia coli isolated from stool samples was seen in children aged 3 or 6 months in the co-trimoxazole group than in the placebo group (p=0·001 and p=0·01, respectively). 572 (20%) children were breastfed. HIV infection and mortality did not differ significantly by duration of breastfeeding (3·9% for 6 months vs 1·9% for 12 months, p=0·21).. Prophylactic co-trimoxazole seems to offer no survival benefit among HEU children in non-malarial, low-breastfeeding areas with a low risk of mother-to-child transmission of HIV.. US National Institutes of Health.

Topics: Adult; Anti-HIV Agents; Botswana; Breast Feeding; Double-Blind Method; Drug Resistance, Microbial; Escherichia coli; Female; HIV Infections; Hospitalization; Humans; Infant; Infant Death; Infant, Newborn; Infectious Disease Transmission, Vertical; Neutropenia; Perinatal Death; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality.. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.. Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. (Funded by the Medical Research Council and others; REALITY Current Controlled Trials number, ISRCTN43622374 .).

Topics: Adolescent; Adult; Africa South of the Sahara; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Drug Therapy, Combination; Female; HIV Infections; Humans; Isoniazid; Kaplan-Meier Estimate; Male; Middle Aged; Pyridoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Despite declining risk of vertical HIV transmission, prophylactic cotrimoxazole (CTX) remains widely used to reduce morbidity and mortality in the event of HIV infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo-controlled trial of infant CTX prophylaxis, we sought to quantify emergence of antibiotic resistance.. HIV-exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX or placebo between 14 and 34 days of life and continued through 15 months. Stool samples were collected from a subset of participating infants at randomization, three, and six months, and stored at -70°C prior to culture. Specimens that grew Escherichia coli (E. coli) or Klebsiella species (Klebsiella spp.) underwent antibiotic susceptibility testing by Kirby Bauer method using CTX (CTX 1.25/23.75 μg) and Amoxicillin (10 μg) in Mueller Hinton agar. Fisher's exact testing was used to compare prevalence of resistance by randomization arm (CTX/placebo).. A total of 381 stool samples from 220 infants were cultured: 118 at randomization, 151 at three months, and 112 at six-months. E. coli was isolated from 206 specimens and Klebsiella spp. from 138 specimens. Resistance to CTX was common in both E. coli and Klebsiella spp. at the randomization visit (52.2% and 37.7% respectively) and did not differ by study arm. E. Coli isolates from CTX recipients at three and six months had 94.9% and 84.2% CTX resistance, as compared with 51.4% and 57.5% CTX resistance in isolates from placebo recipients (p=0.01). Klebsiella spp. isolates from CTX recipients had 79.0% and 68.8% CTX resistance at three and six months, as compared with 19.1% and 14.3% in isolates from placebo recipients (p<0.01).. HIV-exposed infants randomized to CTX prophylaxis had increased CTX-resistant commensal gastrointestinal bacteria compared with placebo recipients. Additional research is needed to determine the longer-term clinical, microbiologic, and public health consequences of antimicrobial resistance selected by infant CTX prophylaxis.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Botswana; Double-Blind Method; Drug Resistance, Bacterial; Escherichia coli; Feces; Female; Gastrointestinal Microbiome; HIV Infections; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination

 Cotrimoxazole (CTX) discontinuation increases malaria incidence in human immunodeficiency virus (HIV)-infected individuals. Rates, quantity, and timing of parasitemia rebound following CTX remain undefined..  Serial specimens from a trial of HIV-infected individuals receiving antiretroviral treatment (ART) randomized to continue (the CTX arm) or discontinue (the STOP-CTX arm) were examined for malaria parasites by quantitative reverse transcription polymerase chain reaction (PCR). Specimens obtained at enrollment and then quarterly for 12 months and at sick visits were assessed; multiplicity of infection was evaluated by PCR that targeted the polymorphic msp-1/msp-2 alleles..  Discontinuation of CTX by HIV-infected adults receiving ART resulted in progressive increases in malaria parasitemia prevalence and burden..  NCT01425073.

Topics: Adult; Anti-HIV Agents; Antimalarials; Female; HIV Infections; Humans; Kenya; Malaria; Male; Medication Adherence; Parasite Load; Parasitemia; Plasmodium falciparum; Polymerase Chain Reaction; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants.. To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded.. A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2-6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival.. It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29-0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41-0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital.. In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Double-Blind Method; Female; HIV Infections; Humans; Infant; Malawi; Male; Placebos; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Secondary Prevention; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa.. The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices.. Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Delivery of Health Care; Disease Progression; Female; Health Care Costs; Health Resources; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Public Health Systems Research; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Zambia

Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial.. HIV-infected Ugandan adults stable on ART and CTX with CD4 cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes.. A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2-10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74-4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18-0.49). There was one malaria-related death (CTX arm).. HIV-infected adults - who are stable on ART and stop prophylactic CTX - experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; Chemoprevention; Double-Blind Method; Female; HIV Infections; Humans; Incidence; Malaria; Male; Middle Aged; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed.. A double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters.. Sulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53% decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days.. Although a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.

Topics: Adolescent; Adult; Antimalarials; Double-Blind Method; Female; HIV Infections; Humans; Kenya; Malaria; Male; Mefloquine; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.. Of 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models.. After a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95% CI, 1.5-2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2-13.4) versus 1.2/100 child-years (0.8-1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI. Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95% CI, 1.1-8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001).. TB incidence varies over time following ART initiation, and is particularly high during the first 3 months post-ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB.

Topics: Anti-Infective Agents; Child; Child, Preschool; Comorbidity; Female; HIV Infections; Humans; Incidence; Infant; Male; Mass Screening; Proportional Hazards Models; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Uganda; Zimbabwe

No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.. A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.. The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).. PACTR201311000621110 and DOH-27-0614-4728; Pre-results.

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Breast Feeding; Cause of Death; Diarrhea; Female; Growth Disorders; HIV; HIV Infections; Humans; Incidence; Infant; Infant Health; Infant Mortality; Infectious Disease Transmission, Vertical; Male; Morbidity; Mothers; Pneumonia; Pregnancy; Pregnancy Complications, Infectious; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination

The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX).. This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use.. 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30.. The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Retroviral Agents; Antimalarials; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Chemoprevention; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Male; Middle Aged; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Before antiretroviral therapy (ART) became widely available in sub-Saharan Africa, several studies demonstrated that daily trimethoprim-sulfamethoxazole (TS) prophylaxis reduced morbidity and mortality among HIV-infected adults. As a result, the World Health Organization (WHO) recommended administering TS prophylaxis to this group. However, the applicability of the results to individuals taking ART and living in sub-Saharan Africa has not been definitively evaluated. This study aims to determine if TS prophylaxis benefits HIV-infected Malawian adults after a good response to ART. If TS prophylaxis does indeed show benefit, it is important to determine if this is due to its antibacterial and/or antimalarial properties.. A randomized, controlled, open-label, phase III trial of continued standard of care prophylaxis with daily trimethoprim-sulfamethoxazole (TS) compared to discontinuation of standard of care TS prophylaxis and starting weekly chloroquine (CQ) prophylaxis or discontinuation of standard of care TS prophylaxis. The study will randomize 1400-1500 HIV-infected adults (equally divided over the three study arms) with a nondetectable viral load and a CD4 count of 250/mm(3) or more from antiretroviral therapy clinics in Blantyre and Zomba. The expected rate of primary endpoint events of death and WHO stage 3 and 4 events is 6.8 per 100 person-years of follow-up in all participants. Assuming the number of events follows a Poisson distribution and average participant follow-up after 10 % loss to follow-up is 41.6 months, the study will have approximately 85 % power to rule out a reduction of 35 % or more in primary endpoint events in the TS or CQ arms compared to discontinuation of TS prophylaxis-i.e., to show that discontinuation of TS prophylaxis is noninferior to either TS or CQ, with a noninferiority margin of 35 %. Ethical and regulatory approvals were obtained from the University of Malawi College of Medicine Research Ethics Committee; the Malawi Pharmacy, Medicines and Poisons Board; and the University of Maryland Baltimore Institutional Review Board.. The study began recruitment activities at the Ndirande site in November 2012. The sponsor agreed to extend and expand the study in early 2015, and a second site, Zomba, was added for recruitment and follow-up in mid-2015.. ClinicalTrials.gov Identifier: NCT01650558 (registered on 6 July 2012).. Letter of amendment #1 to the DAIDS-ES 10822 TSCQ Malawi Protocol, Version 4.0, 16 December 2014.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Retroviral Agents; Antimalarials; Chloroquine; Drug Administration Schedule; HIV Infections; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate whether cotrimoxazole prophylaxis prevents common skin conditions in HIV-infected children.. Open-label randomized controlled trial of continuing versus stopping daily cotrimoxazole (post-hoc analysis).. Three sites in Uganda and one in Zimbabwe.. A total of 758 children aged more than 3 years receiving antiretroviral therapy (ART) for more than 96 weeks in the ARROW trial were randomized to stop (n = 382) or continue (n = 376) cotrimoxazole after median (interquartile range) 2.1(1.8, 2.2) years on ART.. Continuing versus stopping daily cotrimoxazole.. Nurses screened for signs/symptoms at 6-week visits. This was a secondary analysis of ARROW trial data, with skin complaints categorized blind to randomization as bacterial, fungal, or viral infections; dermatitis; pruritic papular eruptions (PPEs); or others (blisters, desquamation, ulcers, and urticaria). Proportions ever reporting each skin complaint were compared across randomized groups using logistic regression.. At randomization, median (interquartile range) age was 7 (4, 11) years and CD4 was 33% (26, 39); 73% had WHO stage 3/4 disease. Fewer children continuing cotrimoxazole reported bacterial skin infections over median 2 years follow-up (15 versus 33%, respectively; P < 0.001), with similar trends for PPE (P = 0.06) and other skin complaints (P = 0.11), but not for fungal (P = 0.45) or viral (P = 0.23) infections or dermatitis (P = 1.0). Bacterial skin infections were also reported at significantly fewer clinic visits (1.2 versus 3.0%, P < 0.001). Independent of cotrimoxazole, bacterial skin infections were more common in children aged 6-8 years, with current CD4 cell count less than 500 cells/μl, WHO stage 3/4, less time on ART, and lower socio-economic status.. Long-term cotrimoxazole prophylaxis reduces common skin complaints, highlighting an additional benefit for long-term prophylaxis in sub-Saharan Africa.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Child, Preschool; Female; HIV Infections; Humans; Incidence; Male; Skin Diseases, Bacterial; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Zimbabwe

To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART.. The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings.. Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4 monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio = $769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to $12.0 per patient-year to ensure continued provision of cotrimoxazole.. Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources.

Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Child; Child, Preschool; Cost-Benefit Analysis; Female; Health Care Costs; HIV Infections; Humans; Male; Quality-Adjusted Life Years; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Zimbabwe

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design.. COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events.. Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations.. This paper describes the design and methodological considerations important for the conduct of CTX cessation studies.

Topics: AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Administration Schedule; Female; HIV Infections; Humans; Incidence; Male; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4(+) T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women.

Topics: Adult; Antimalarials; Benin; Drug Combinations; Female; HIV Infections; Humans; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-5; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Prospective Studies; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha; Young Adult

Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.. We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.. At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.. CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.

Topics: Adult; Antimalarials; Benin; Chemoprevention; Dizziness; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Infant; Infant, Newborn; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Human immunodeficiency virus (HIV) and malaria during pregnancy cause substantial perinatal mortality. As co-trimoxazole (CMX) protects children and HIV-positive adults against malaria, we compared the effectiveness of daily CMX with sulfadoxine-pyrimethamine intermittent preventive treatment (IPT-SP) on malaria risk in HIV-positive pregnant women in a Plasmodium falciparum-endemic African area..  From January 2009 to April 2011, we included in a randomized noninferiority trial all HIV type 1-infected pregnant women (≤28 weeks' gestation, CD4 count ≥200 cells/µL, hemoglobin level ≥7 g/L) in 19 health centers in Togo. Women were randomly assigned to daily 800 mg/160 mg CMX, or IPT-SP. The primary outcome was the proportion of malaria-free pregnancies. Other outcomes included malaria incidence, parasitemia, placental malaria, anemia, and infants' birth weight.. Of 264 women randomly assigned to the CMX or IPT-SP group, 126 of 132 and 124 of 132, respectively, were included in the analysis. There were 33 confirmed cases of clinical malaria among 31 women in the CMX group, and 19 among 19 women in the IPT-SP group. Ninety-five of 126 (75.4%) women in the CMX group and 105 of 124 (84.7%) in the IPT-SP group remained malaria-free during their pregnancy (difference, 9.3%; 95% confidence interval [CI], -.53 to 19.1, not meeting the predefined noninferiority criterion). The incidence rate in intention-to-treat analysis was 108.8 malaria episodes per 100 person-years in CMX (95% CI, 105.4-112.2) and 90.1 in IPT-SP (95% CI, 86.8-93.4) (not significant). Prevalence of parasitemia was 16.7% in the CMX group vs 28% in the IPT-SP group (P = .02). Histology revealed 20.3% placental malaria in the CMX group vs. 24.6% in the IPT-SP group (not significant). Grade 3-4 anemia was more frequent in the CMX group (10% vs 4%; P = .008). No pregnant women died. Median birth weight was similar..  Daily CMX was not noninferior to IPT-SP for preventing maternal malaria but safe and at least similar regarding parasitemia or placental malaria and birth outcomes. Clinical Trials Registration  ISRCTN98835811.

Topics: Adolescent; Adult; Antimalarials; Drug Combinations; Female; HIV Infections; Humans; Incidence; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine; Togo; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.. We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe. Eligible participants were older than 3 years of age, had been receiving ART for more than 96 weeks, were using insecticide-treated bed nets (in malaria-endemic areas), and had not had Pneumocystis jirovecii pneumonia. Coprimary end points were hospitalization or death and adverse events of grade 3 or 4.. A total of 758 participants were randomly assigned to stop or continue co-trimoxazole (382 and 376 participants, respectively), after receiving ART for a median of 2.1 years (interquartile range, 1.8 to 2.3). The median age was 7.9 years (interquartile range, 4.6 to 11.1), and the median CD4 T-cell percentage was 33% (interquartile range, 26 to 39). Participants who stopped co-trimoxazole had higher rates of hospitalization or death than those who continued (72 participants [19%] vs. 48 [13%]; hazard ratio, 1.64; 95% confidence interval [CI], 1.14 to 2.37; P = 0.007; noninferiority not shown). There was no evidence of variation across ages (P=0.93 for interaction). A total of 2 participants in the prophylaxis-stopped group (1%) died, as did 3 in the prophylaxis-continued group (1%). Most hospitalizations in the prophylaxis-stopped group were for malaria (49 events, vs. 21 in the prophylaxis-continued group) or infections other than malaria (53 vs. 25), particularly pneumonia, sepsis, and meningitis. Rates of adverse events of grade 3 or 4 were similar in the two groups (hazard ratio, 1.20; 95% CI, 0.83 to 1.72; P=0.33), but more grade 4 adverse events occurred in the prophylaxis-stopped group (hazard ratio, 2.04; 95% CI, 0.99 to 4.22; P=0.05), with anemia accounting for the largest number of events (12, vs. 2 with continued prophylaxis).. Continuing co-trimoxazole prophylaxis after 96 weeks of ART was beneficial, as compared with stopping prophylaxis, with fewer hospitalizations for both malaria and infection not related to malaria. (Funded by the United Kingdom Medical Research Council and others; ARROW Current Controlled Trials number, ISRCTN24791884.).

Topics: Adolescent; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Female; Follow-Up Studies; HIV Infections; Hospitalization; Humans; Kaplan-Meier Estimate; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment; Zimbabwe

Shortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infected patients with tuberculosis. A better understanding of causes and determinants of death may lead to new strategies to further enhance survival.. We assessed mortality rates, causes of death, and factors of mortality in Cambodian HIV-infected adults with CD4 count ≤200 cells/µL and tuberculosis, randomized to initiate ART either 2 weeks (early ART) or 8 weeks (late ART) after tuberculosis treatment onset in the CAMELIA clinical trial.. Six hundred sixty-one patients enrolled contributed to 1366.1 person-years of follow-up; 149 (22.5%) died. There were 8.3 deaths per 100 person-years (95% confidence interval [CI], 6.4-10.7) in the early-ART group and 13.8 deaths per 100 person-years (95% CI, 11.2-16.9) in the late-ART group (P = .002). Tuberculosis was the primary cause of death (28%), followed by other HIV-associated conditions (19%). Factors independently associated with mortality in the first 26 weeks were the age, body mass index, hemoglobin, interrupted or ineffective tuberculosis treatment before identification of drug resistance, disseminated tuberculosis, and nontuberculous mycobacterial disease. After 50 weeks in the trial, the most frequent causes of death were non-HIV related or tuberculosis related, including drug toxicity; factors associated with mortality were late ART, loss to follow-up, and absence of cotrimoxazole prophylaxis.. Despite ART introduction, mortality remained high, with tuberculosis as the leading cause of death. Reducing tuberculosis-related mortality remains a challenge in resource-limited settings and requires innovative strategies. Clinical Trials Registration. NCT00226434.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; CD4 Lymphocyte Count; Cohort Studies; Female; Follow-Up Studies; HIV Infections; Humans; Immunocompromised Host; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.. Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.. Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.. Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.. Clinicaltrials.gov NCT00711906.

Topics: Adult; Antimalarials; Birth Weight; Drug Administration Schedule; Female; Gestational Age; HIV Infections; Humans; Malaria; Male; Maternal Exposure; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pregnancy Outcome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zambia

Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria.. HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receive lopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach.. Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms.. Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART.. NCT00993031.

Topics: Adolescent; Adult; Alkynes; Anti-HIV Agents; Antimalarials; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; Female; HIV Infections; Humans; Infant, Newborn; Lopinavir; Malaria; Pregnancy; Pregnancy Complications, Infectious; Ritonavir; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).. A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.. An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.. ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

Topics: Adult; Antimalarials; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Kenya; Malaria; Mefloquine; Mozambique; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pregnancy Outcome; Tanzania; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age until breastfeeding cessation and exclusion of HIV infection. We have previously reported on the effectiveness of continuation of co-trimoxazole prophylaxis up to age 2 years in these children. We assessed the protective efficacy and safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children.. We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. We enrolled HIV-exposed infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding cessation and HIV-status confirmation. At the end of breastfeeding, children who remained HIV-uninfected were randomly assigned (1:1) to discontinue co-trimoxazole or to continue taking it up to age 2 years. At age 2 years, children who continued co-trimoxazole prophylaxis were randomly assigned (1:1) to discontinue or continue prophylaxis from age 2 years to age 4 years. The primary outcome was incidence of malaria (defined as the number of treatments for new episodes of malaria diagnosed with positive thick smear) at age 4 years. For additional comparisons, we observed 48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children who never received prophylaxis. We measured grade 3 and 4 serious adverse events and hospital admissions. All children were followed up to age 5 years and all analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00527800.. 203 HIV-exposed infants were enrolled between Aug 10, 2007, and March 28, 2008. After breastfeeding ended, 185 children were not infected with HIV and were randomly assigned to stop (n=87) or continue (n=98) co-trimoxazole up to age 2 years. At age 2 years, 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were randomly assigned to discontinue (n=46) or continue (n=45) co-trimoxazole from age 2 years to age 4 years. We recorded 243 malaria episodes (2·91 per person-years) in the 45 HIV-exposed children assigned to continue co-trimoxazole until age 4 years compared with 503 episodes (5·60 per person-years) in the 46 children assigned to stop co-trimoxazole at age 2 years (incidence rate ratio 0·53, 95% CI 0·39-0·71; p< 0·0001). There was no evidence of malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped co-trimoxazole at age 2 years, but incidence increased significantly in HIV-exposed children who stopped co-trimoxazole at age 4 years (odds ratio 1·78, 95% CI 1·19-2·66; p= 0·005). Incidence of grade 3 or 4 serious adverse events, hospital admissions, or deaths did not significantly differ between HIV-exposed, HIV-unexposed, and HIV-infected children.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Breast Feeding; CD4 Lymphocyte Count; Child, Preschool; Female; HIV Infections; Humans; Infant; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Co-infection with malaria parasite and HIV is an emerging public health problem in tropical areas, particularly in pregnant women, and management of the concurrent effects of these two infections is challenging. Co-trimoxazole is a sulfamide preparation used to prevent opportunistic infections in HIV-infected patients, and many studies have reported that it has significant activity against malaria. As the efficacy of intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) against malaria is decreasing, co-trimoxazole might be an alternative for preventing malaria among HIV-infected populations. The aim of this study is to compare the effectiveness of SP-IPT, which is recommended for the prevention of malaria during pregnancy in the Central African Republic, with that of a daily dose of co-trimoxazole against P. falciparum infections among HIV-infected pregnant women in Bangui, the capital of the Central African Republic.. The MACOMBA study (MAternity and COntrol of Malaria-HIV co-infection in BAngui) is a multicentre open-label randomized clinical trial conducted at four maternity hospitals in Bangui. All HIV-infected pregnant women presenting for an antenatal clinic visit between the weeks 16 and 28 of amenorrhoea, with a CD4 count of more than 350 cells/mm3, will be eligible. All the women will provide written consent before being enrolled in the study and will then be randomly allocated to either SP-IPT (25 mg of sulfadoxine and 1.25 mg of pyrimethamine) or daily co-trimoxazole doses (960 mg per dose). The primary end-point is the placental malaria parasitaemia rate at delivery. Other main outcome measures include the number of malaria episodes during pregnancy, safety, and treatment compliance. Furthermore, the frequency of molecular resistance markers dhfr and dhps will be measured.. In this trial, we seek to confirm whether co-trimoxazole is operationally suitable to replace SP-IPT in order to prevent malaria among pregnant women infected with HIV in the Central African Republic.. ClinicalTrials.gov Identifier: NCT01746199.

Topics: Antimalarials; Central African Republic; Clinical Protocols; Coinfection; Drug Administration Schedule; Drug Combinations; Female; Folic Acid Antagonists; HIV Infections; Hospitals, Maternity; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Pyrimethamine; Research Design; Sulfadoxine; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp).. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count.. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ μ L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ μ L, 95% CI: -58.6, -8.8).. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Infant, Low Birth Weight; Malaria; Malawi; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Artemisinin-based combination therapies (ACTs) and trimethoprim-sulfamethoxazole (TS) prophylaxis are important tools for malaria control, but there are concerns about their effect on gametocytes, the stage of the parasite responsible for transmission. We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Uganda. Study participants were randomized to artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) for all treatments of uncomplicated malaria (N = 4,380) as well as TS prophylaxis for different durations. The risks of gametocytemia detected by microscopy in the 28 days after antimalarial therapy were compared using multivariate analyses. The risk of gametocyte detection was significantly higher in patients treated with DP compared with AL (adjusted relative risk = 1.85, P < 0.001) and among children prescribed TS prophylaxis (adjusted relative risk = 1.76, P < 0.001). The risk of gametocytemia and its potential for increasing transmission should be considered when evaluating different ACTs and TS prophylaxis for malaria control.

Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluorenes; HIV Infections; Humans; Infant; Longitudinal Studies; Malaria, Falciparum; Multivariate Analysis; Parasitemia; Plasmodium falciparum; Post-Exposure Prophylaxis; Prevalence; Proportional Hazards Models; Quinolines; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Trophozoites; Uganda

Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/μL. However, this practice has not been evaluated in sub-Saharan Africa.. Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/μL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/μL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea.. At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/μL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001).. HIV-infected adults on ART with CD4 counts >200 cells/μL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Diarrhea; Female; HIV Infections; Humans; Incidence; Malaria; Male; Risk Assessment; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment

The World Health Organization guidelines recommend cotrimoxazole prophylactic treatment (CPT) for all HIV-exposed infants from age 6 weeks to the cessation of breastfeeding and the exclusion of HIV infection. There are limited data on the effects of CPT among this population of infants. We examined the effects of CPT on adverse health outcomes among HIV-exposed infants during the first 36 weeks of life using data from the Breastfeeding, Antiretrovirals and Nutrition study, a large clinical trial of antiretroviral drugs given to the mother or infant for the prevention of HIV transmission during breastfeeding.. For the analysis, we assigned a status of CPT-exposed to infants who were participating in the study after the CPT program started. We estimated unadjusted and adjusted hazard ratios for the effect of CPT status on time to incident malaria, severe illness or death, anemia, and weight-for-age Z score < -2.0. Participation in the study was limited to focus exclusively on HIV-exposed, uninfected infants.. The hazard ratio for the effect of CPT on incident malaria was 0.35 (95% confidence interval: 0.21, 0.57) during the first 10 weeks of CPT exposure and 0.93 (95% confidence interval: 0.67, 1.29) for the remaining 20 weeks. CPT was not associated with the other outcomes examined.. CPT offered temporary protection against malaria among HIV-exposed, uninfected infants. However, CPT offered no protection against anemia, low weight for age or the collapsed outcome of severe illness or death.

Topics: Anemia; Anti-Retroviral Agents; Antibiotic Prophylaxis; Antimalarials; Body Weight; Breast Feeding; Chi-Square Distribution; Female; HIV Infections; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Malaria; Mothers; Statistics, Nonparametric; Trimethoprim, Sulfamethoxazole Drug Combination

The impact of cotrimoxazole (CTX) on growth and/or anemia was investigated in 541 human immunodeficiency virus-infected, antiretroviral therapy-naive Zambian children enrolled in the Children with HIV Antibiotic Prophylaxis trial. Compared with children randomized to receive placebo, children randomized to receive CTX had slower decreases in weight-for-age (P=.04) and height-for-age (P=.01), and greater increase in hemoglobin level (P=.01). These findings argue for expanded early CTX use.

Topics: Adolescent; Anemia; Antimalarials; Body Height; Body Weight; Chemoprevention; Child; Child Development; Child, Preschool; Female; HIV Infections; Humans; Infant; Malaria; Male; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.. Non-blinded randomised control trial. Tororo district, rural Uganda, an area of high malaria transmission intensity. 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age. Co-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.. Incidence of malaria, calculated as the number of antimalarial treatments per person year.. The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.. Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.

Topics: Antimalarials; Breast Feeding; Diarrhea, Infantile; Female; HIV Infections; HIV Seronegativity; Humans; Incidence; Infant; Malaria; Pregnancy; Pregnancy Complications, Infectious; Respiratory Tract Infections; Rural Health; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Bacteremia contributes to morbidity of HIV-infected children. In a randomized controlled trial evaluating trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, 47 bacteremias were detected. The incidence rate of bacteremia increased in the first 3 months after starting combination antiretroviral therapy (cART), but decreased by 74% once children were established on cART for more than 3 months. Children should be prioritized for early cART.

Topics: Anti-HIV Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Bacteremia; Child; Child, Preschool; Female; HIV Infections; Humans; Incidence; Infant; Male; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown.. We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses.. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04).. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration. ISRCTN63659091.

Topics: Adult; Alkynes; Anti-HIV Agents; Anti-Inflammatory Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; Cyclopropanes; Dexamethasone; Double-Blind Method; Female; HIV Infections; Humans; Lamivudine; Male; Placebos; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Meningeal; Zidovudine

To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy (cART).. A cohort study.. Using proportional hazards modeling, we compared mortality during the first 12 months after cART initiation among patients receiving CPT with patients not receiving CPT. We adjusted for clinic level confounding throughout.. We included 14 097 patients starting cART between January 2003 and January 2008, 62% of whom were men, the median CD4 cell count was 132 cells/microl, and 1289 died (11%). The baseline median CD4 cell count was lower (118 vs. 153 cells/microl) among the 7508 patients who received CPT compared with the 6589 patients who did not. In adjusted multivariate modeling, stratifying for baseline CD4 cell count and WHO stage, CPT reduced mortality overall (hazard ratio 0.64, P < 0.001) and for all individuals with CD4 cell count below 200 cells/microl or WHO clinical stage 3 or 4 conditions but did not reduce mortality for patients with both CD4 cell count above 200 cells/microl and WHO clinical stage 1 or 2.. We demonstrated a 36% reduction in mortality extending to patients associated with CPT when used with cART that extended to patients with CD4 cell count above 350 cells/microl in a setting with minimal malaria and high rates of cotrimoxazole-resistant bacteria. This provides important additional data toward efforts to increase CPT provision among all cART initiators in resource limited settings.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Drug Administration Schedule; Epidemiologic Methods; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; South Africa; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae as major causes of childhood mortality in HIV-infected children was investigated since these are unclear. Representative nasopharyngeal swabs were taken prior to randomization for 181 of 534 children (92 on cotrimoxazole and 89 on placebo). Bacterial identification and antibiotic susceptibility were performed by routine methods. Due to reduced mortality, prophylactic cotrimoxazole increased the median time from randomization to the last specimen from 48 to 56 months (P = 0.001). The carriage of H. influenzae was unaltered by cotrimoxazole. Carriage of S. pneumoniae increased slightly in both arms but was not statistically significant in the placebo arm. In S. pneumoniae switching between carriage and no carriage in consecutive pairs of samples was unaffected by cotrimoxazole (P = 0.18) with a suggestion that the probability of remaining carriage free was lower (P = 0.10). In H. influenzae cotrimoxazole decreased switching from carriage to no carriage (P = 0.02). Cotrimoxazole resistance levels were higher in postbaseline samples in the cotrimoxazole arm than in the placebo arm (S. pneumoniae, P < 0.0001; H. influenzae, P = 0.005). Cotrimoxazole decreased switching from cotrimoxazole resistance to cotrimoxazole sensitivity in S. pneumoniae (P = 0.002) and reduced the chance of H. influenzae remaining cotrimoxazole sensitive (P = 0.05). No associations were observed between the percentage of CD4 (CD4%), the change in CD4% from baseline, child age at date of specimen, child gender, or sampling month with carriage of either pathogen.

Topics: Anti-Infective Agents; Child, Preschool; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; HIV Infections; Humans; Male; Pneumococcal Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Cotrimoxazole preventive therapy (CPT) reduces morbidity and mortality in HIV-infected children. The WHO recommends prolonged daily CPT for HIV-infected infants and children. In adults, intermittent CPT has been associated with less adverse events than daily, with increased tolerability and equal efficacy. We investigated the efficacy and tolerability of intermittent CPT compared with daily CPT in HIV-infected children over a 5-year period.. A prospective randomized controlled study.. HIV-infected children aged at least 8 weeks were randomized to thrice weekly or daily CPT. Outcome measures were mortality, bacterial infections, hospitalizations and adverse events.. Three hundred and twenty-four children (median age 23 months) were followed for 672 child-years; 165 (51%) were randomized to intermittent CPT. Most children (287, 89%) were Centers for Disease Control and Prevention clinical category B or C; 207 (64%) received HAART during the study. Mortality (53 deaths, 16%) was similar in the intermittent CPT compared with the daily CPT group {24 (14%) vs. 29 (18%), hazard ratio 0.75 [95% confidence interval (CI) 0.44-1.29]}. The predominant causes of death in both groups were sepsis (17, 32%), pneumonia (13, 25%) or diarrhoea (8, 15%). Intermittent CPT was associated with more bacteraemias [incidence rate ratio 2.36 (95% CI 1.21-4.86)]. Children receiving intermittent CPT also spent more days in hospital [incidence rate ratio 1.15 (95% CI 1.04-1.28)]. The rate of serious adverse events was similar between groups [incidence rate ratio 1.07 (95% CI 0.58-2.02)].. Intermittent CPT was associated with more invasive bacterial disease than daily CPT, but survival was similar. Both regimens were well tolerated. On balance, daily CPT remains preferable to intermittent therapy for HIV-infected children.

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Child, Preschool; Female; HIV Infections; HIV-1; Hospitalization; Humans; Infant; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

To determine if exposure to trimethoprim-sulfamethoxazole (TMP-SMX) causes a defect in peripheral B-cell function among patients with the human immunodeficiency virus (HIV) who are receiving zidovudine antiretroviral therapy.. Prospective, single-center, single-group, case-crossover design with a 4-week exposure period.. University-affiliated infectious diseases outpatient clinic.. Fourteen HIV-infected adult men receiving zidovudine, who had CD4(+) cell counts above 350 cells/mm(3) and undetectable viral loads.. Patients were administered a 28-day course of TMP 160 mg-SMX 800 mg/day (one double-strength tablet/day). Peripheral blood mononuclear cells (PBMCs) were obtained and isolated before and after exposure to TMP-SMX. Cells were cultured ex vivo with three mitogens of differing immunologic properties: pokeweed mitogen ([PWM] T-cell-dependent B-cell mitogen), Staphylococcus aureus Cowan ([SAC] T-cell-independent B-cell mitogen), and phytohemagglutinin A ([PHA] T-cell mitogen). Functionality of the B and T lymphocytes was then assessed.. Proliferative capacity, cytokine secretion, and antibody production were measured and compared before and after TMP-SMX exposure. Reduced proliferative capacities of both PBMC and B cells stimulated with mitogens were observed at the 3-day culture time point in response to PWM, PHA, and SAC (p=0.029, 0.028, and 0.026, respectively). Proliferative capacity at day 7 of culture was not significantly different for any condition examined. Cytokine production was not altered by combination drug exposure after 10 days of culture when cells were stimulated with either PWM or PHA. Although antibody responses to PWM and PHA were similar, total immunoglobulin G concentration was lower in cells stimulated with SAC in samples obtained after TMP-SMX regimen completion compared with those obtained before exposure (p=0.005).. Although these data were affected by limitations in power and study design, they suggest that peripheral B-lymphocyte function is altered as a result of TMP-SMX exposure in HIV-infected patients concurrently receiving zidovudine. Further study of this effect is warranted.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; B-Lymphocytes; Cross-Over Studies; Cytokines; Drug Therapy, Combination; Female; HIV Infections; Humans; Immunoglobulin G; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To assess the impact of prophylactic oral co-trimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis.. Double blind placebo controlled randomised clinical trial.. Two groups of antiretroviral treatment naive adults with HIV infection: patients newly diagnosed as having tuberculosis and receiving tuberculosis treatment either for the first time or for retreatment after relapse; previously treated patients not receiving treatment.. Oral co-trimoxazole or matching placebo daily. Primary outcome measures Time to death and occurrence of serious adverse events related to study drug.. 1003 patients were randomised: 835 (416 co-trimoxazole, 419 placebo) were receiving treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo) receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on treatment but had received treatment in the past. Of 835 participants receiving tuberculosis treatment, follow-up information was available for 757, with a total of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163 placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100 person years. In the Cox regression analysis, the hazard ratio for death (co-trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect of co-trimoxazole waned with time, possibly owing to falling adherence levels; in a per protocol analysis based on patients who spent at least 90% of their time at risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93).. Prophylaxis with co-trimoxazole reduces mortality in HIV infected adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well tolerated.. Current Controlled Trials ISRCTN15281875.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Infective Agents; Double-Blind Method; Epidemiologic Methods; Female; HIV Infections; Humans; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

To assess the potential of cotrimoxazole and tenofovir, drugs which are inhibitors and/or substrates of renal transporters, to alter the pharmacokinetic profile of maraviroc.. Two randomized, placebo-controlled, two-way crossover studies were conducted in healthy male and female subjects. In study 1, 16 subjects, aged 18-45 years, received maraviroc (300 mg b.i.d.) with and without cotrimoxazole (960 mg b.i.d.; 160 mg trimethoprim and 800 mg sulfamethoxazole). In study 2, 12 subjects, aged 21-45 years, received maraviroc (300 mg b.i.d.) with and without tenofovir (300 mg q.d.). For study 1, blood was collected predose and on days 1-7. In study 2, blood was collected predose, on day 1 and days 3-7. In both studies, blood was collected at intervals up to 12 h postdose on day 7. Urine was collected on day 7, 0-12 h post morning dose. Blood and urine were analysed for maraviroc using liquid chromatography/tandem mass spectrometry.. The geometric mean ratios for C(max) and AUC(12) were 119% and 111%, respectively, for maraviroc plus cotrimoxazole and 104% and 103%, respectively, for maraviroc plus tenofovir, compared with maraviroc plus placebo. Renal clearance of maraviroc plus placebo was 8.3 l h(-1) and 8.5 l h(-1) and was 7.8 l h(-1) for maraviroc plus cotrimoxazole and maraviroc plus tenofovir. There were no serious or severe adverse events or any clinically significant changes in laboratory tests, blood pressure, or electrocardiograms.. Neither cotrimoxazole nor tenofovir caused a clinically significant effect on the pharmacokinetics of maraviroc. Maraviroc 300 mg b.i.d. was well tolerated when co-administered with either cotrimoxazole or tenofovir.

Topics: Adenine; Adolescent; Adult; Anti-HIV Agents; Anti-Infective Agents; CCR5 Receptor Antagonists; Cyclohexanes; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Maraviroc; Middle Aged; Organophosphonates; Receptors, CCR5; Statistics as Topic; Tenofovir; Triazoles; Trimethoprim, Sulfamethoxazole Drug Combination

Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)-infected populations.. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines.. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; p = .08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; p < .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, <750 cells/mm(3)). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; p < .001).. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.

Topics: Amodiaquine; Anti-HIV Agents; Antimalarials; Artemisinins; Artesunate; Chemoprevention; Child; Child, Preschool; Drug Therapy, Combination; HIV Infections; Humans; Infant; Malaria; Neutropenia; Sesquiterpenes; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire.. Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001-2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995-2000), used as a reference group. HIV-infected pregnant women > or = 32-36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV +/- 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48-72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model.. Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%-81%) and 77% in Ditrame (95%CI: 65%-89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3-1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2-11.2; p = 0.01).. Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.

Topics: Adult; Anti-Infective Agents; Anti-Retroviral Agents; Cohort Studies; Cote d'Ivoire; Early Diagnosis; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Kaplan-Meier Estimate; Male; Pregnancy; Pregnancy Complications, Infectious; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

Written information to promote patient education is being increasingly recognized as an integral part of quality health care. The main objective of this study was to evaluate the effect of distributing a patient information leaflet (PIL) on knowledge acquisition and recall. Two different PILs were designed for co-trimoxazole tablets: a simple, shorter PIL that incorporated pictograms and text and a text-only PIL that was longer and more complex. Human immunodeficiency virus-positive participants on chronic co-trimoxazole therapy were enrolled from five local primary health care clinics in Grahamstown, South Africa, and were randomly allocated to a Control Group (no PIL), Group A (text-only PIL) or Group B (simple PIL with pictograms). At the preliminary interview, demographic data were collected and the tablets dispensed according to normal clinic protocol. In a follow-up interview approximately 14 days later, participant medicines knowledge was investigated by asking a series of questions. The mean percentage for medicines knowledge was significantly higher in the group that received the simple PIL incorporating pictograms (76.3%), compared with both the Control Group (43.3%) and the group who received the longer, text-only PIL (50.9%). This study reinforces the value of providing patients with an appropriately designed PIL to inform appropriate medicine-taking behaviour.

Topics: Adolescent; Adult; Anti-Infective Agents; Female; Health Knowledge, Attitudes, Practice; HIV Infections; Humans; Male; Pamphlets; Patient Education as Topic; Socioeconomic Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.. CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups.. Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)].. Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.

Topics: Anti-Infective Agents; Antitubercular Agents; Cause of Death; CD4 Lymphocyte Count; Child; Child, Preschool; Disease Progression; Drug Resistance, Bacterial; Empyema; HIV; HIV Infections; Hospital Mortality; Hospitalization; Humans; Infant; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Data on the population effectiveness of cotrimoxazole prophylaxis and antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected African children are few.. A total of 534 Zambian children with HIV infection were randomized to receive daily cotrimoxazole prophylaxis or placebo in the Children with HIV Antibiotic Prophylaxis trial. Following trial closure, children who received the placebo initiated cotrimoxazole prophylaxis, and all children were observed in a closed cohort. Mortality and hospital admission rates were compared, over calendar time, in 9-month periods: trial recruitment (March 2001 to April 2002, May 2002 to January 2003), trial follow-up to closure (February 2003 to October 2003), initial follow-up posttrial (November 2003 to July 2004), and early and later ART availability (August 2004 to April 2005, and May 2005 to May 2006, respectively).. A total of 546 child-years of follow-up, 40 deaths, and 80 hospital admissions were observed between the time of trial closure and June 2006. A total of 117 of 283 children who were alive at trial closure received ART in the posttrial period (median child age at first use of ART, 8.8 years). Rates decreased in both groups during the trial period, suggesting a survivorship effect. Mortality and hospital admission rates before trial closure were 14 (95% confidence interval [CI], 9-21) deaths per 100 child-years and 24 (95% CI, 15-39) hospital admissions per 100 child-years, respectively, for children who were receiving cotrimoxazole, and were 23 (95% CI, 16-34) deaths per 100 child-years and 35 (95% CI, 23-53) hospital admissions per 100 child-years, respectively, for children who were receiving the placebo. After trial closure, rates remained stable in the cotrimoxazole group, but decreased to 15 (95% CI, 8-26) deaths per 100 child-years and 19 (95% CI, 10-41) hospital admissions per 100 child-years, respectively, for the group of children who received placebo and then initiated cotrimoxazole prophylaxis. In both groups combined, mortality rates decreased to 6 (95% CI, 3-11) deaths per 100 child-years and then 2 (95% CI, 0.8-6) deaths per 100 child-years during periods of ART availability; hospital admission rates decreased to 17 (95% CI, 11-27) hospital admissions per 100 child-years and 8 (95% CI, 4-15) hospital admissions per 100 child-years, respectively.. The benefits of once-daily cotrimoxazole prophylaxis continued throughout the trial and after trial closure. Mortality and hospital admissions decreased (by approximately 6-fold and approximately 3-fold, respectively) following ART availability, similar to findings observed in resource-rich countries.

Topics: Adolescent; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cohort Studies; Female; HIV Infections; HIV-1; Hospitalization; Humans; Infant; Male; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

To determine as proof of principle the effect of combination exposure to zidovudine plus trimethoprim-sulfamethoxazole (TMP-SMX) on humoral immune responses to influenza vaccination in patients with human immunodeficiency virus (HIV).. Prospective, open-label trial.. University-affiliated infectious diseases outpatient clinic.. Twenty-three HIV-infected adults receiving antiretroviral therapy, with CD4+ cell counts greater than 350 cells/mm3 and undetectable viral loads.. Patients were assigned to one of four treatment groups: zidovudine (6 patients), TMP-SMX (7), zidovudine plus TMP-SMX (5), or neither drug (5); TMP-SMX was given as a 28-day course. Patients were subsequently immunized with the yearly influenza vaccine, and humoral responses were compared among groups 20-24 days after vaccination.. Antibody responses to influenza A and B were measured, and total and activated T and B cell percentages in the peripheral blood were determined. Mean influenza B-specific serum immunoglobulin (Ig)G titers were significantly lower in patients receiving TMP-SMX alone (0.98 +/- 0.60 reference value, p=0.010) or the combination of zidovudine plus TMP-SMX (0.73 +/- 0.29 reference value, p=0.003) compared with those receiving neither drug (1.95 +/- 0.38 reference value). This corresponded to a significantly lower percentage of patients in the combination group that achieved immunoprotective titers to influenza B compared with the group who received neither drug (control group; 20% vs 100%, p=0.048). In addition, the relationship between serum IgG titer and CD4+ cell count was statistically significantly different for patients exposed to zidovudine plus TMP-SMX versus control patients for both influenza A and B (F statistics 8.72 and 11.70, respectively, compared with critical F value 7.26 for p<0.025). Likewise, the relationship between influenza B serum IgG and CD4+ cell count was different among patients who received TMP-SMX versus those who did not receive TMP-SMX (F statistic 5.95 compared with critical F value 4.56 for p<0.025). No significant differences were observed among T and B cell percentages in the blood.. Combination exposure to zidovudine plus TMP-SMX causes a clinically significant suppression of humoral immune responses to influenza vaccination in HIV-infected patients.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Immunoglobulin G; Immunoglobulin M; Influenza A virus; Influenza B virus; Influenza Vaccines; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.

Topics: Adolescent; Adult; Age Distribution; Anti-Infective Agents; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Female; HIV Infections; Humans; Liver Diseases; Malawi; Male; Middle Aged; Sex Distribution; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Providing written medicines information is being legislated in an increasing number of countries worldwide, with the patient information leaflet (PIL) being the most widely used method for conveying health information. The impact of providing such information on adherence to therapy is reportedly unpredictable. Therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and related opportunistic infections usually involves polytherapy and complex regimens, both of which are risk factors for non-adherence. The objective of this study was to assess the impact of medicines information on adherence to chronic co-trimoxazole therapy in low-literate HIV/AIDS patients.. Two different PILs were designed for co-trimoxazole tablets and were available in both English and isiXhosa. Participants were randomly allocated to a control group (receiving no PIL), group A (receiving a "complex PIL") and group B (receiving a "simple PIL" incorporating pictograms). At the first interview, demographic data were collected and the time, date and day that the participant would take his/her first tablet of the month's course was also documented. In a follow-up interview adherence to therapy was assessed using two methods; self-report and tablet count.. The medicines information materials incorporating simple text and pictograms resulted in significantly improved adherence to therapy in the short term, whereas a non-significant increase in adherence was associated with the availability of the more complex information. This was shown by both the self-reported assessment as well as the tablet count.. This research suggests that appropriately designed written material can have a positive impact in improving adherence and, together with verbal consultation, are essential for enabling patients to make appropriate decisions about their medicine taking.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Anti-HIV Agents; Drug Labeling; Educational Status; Female; HIV Infections; Humans; Male; Patient Compliance; Patient Education as Topic; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear.. In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women.. Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP.. In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted.

Topics: Adolescent; Adult; Antimalarials; Drug Administration Schedule; Drug Combinations; Female; HIV Infections; Humans; Infant, Newborn; Malaria, Falciparum; Malawi; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylaxis is recommended for subgroups of human immunodeficiency virus (HIV)-infected adults and children to reduce all-cause morbidity and mortality. We investigated whether antenatal cotrimoxazole prophylaxis begun during pregnancy for HIV-infected pregnant women with low CD4 cell counts would affect birth outcomes.. Cotrimoxazole prophylaxis was introduced as a routine component of antenatal care for HIV-infected women with CD4 cell counts <200 cells/ micro L during the course of a trial of mother-to-child HIV transmission in Lusaka, Zambia. Rates of preterm delivery, low birth weight, and neonatal mortality were compared for women with low CD4 cell counts before and after its introduction.. Among 255 women with CD4 cell counts <200 cells/ micro L, the percentage of preterm births (< or =34 weeks of gestation) was lower (odds ratio [OR], 0.49 [95% confidence interval {CI}, 0.24-0.98]) after cotrimoxazole prophylaxis was introduced than before; there was a significant decrease in neonatal mortality (9% to 0%; P=.01) and a trend toward increased birth weight ( beta =114 g [95% CI, -42 to 271 g]). In contrast, there were no significant changes in these parameters over the same time interval among women with CD4 cell counts > or =200 cells/ micro L.Conclusion. Antenatal provision of cotrimoxazole for HIV-infected pregnant women with low CD4 cell counts may have indirect benefits for neonatal health.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.. A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Atovaquone; Azithromycin; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV).. We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy.. After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations.. Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries.

Topics: Anti-Infective Agents; Child, Preschool; Confidence Intervals; Dietary Supplements; Double-Blind Method; Female; HIV Infections; Humans; Infant; Male; Morbidity; Nutritional Status; Risk Factors; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Vitamin A; Vitamin A Deficiency

The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown.. To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members.. Prospective cohort in rural Uganda.. A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months.. During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14-0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53-0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45-0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36-0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1-8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41).. Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Child; Child, Preschool; Cohort Studies; Diarrhea; Disease Transmission, Infectious; Drug Resistance; Family; Family Health; Female; HIV Infections; Humans; Infant; Infant, Newborn; Male; Middle Aged; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

To assess the efficacy and safety of two different dosages of cotrimoxazole (CTX) in prophylaxis in HIV-positive new smear-positive pulmonary tuberculosis (TB) patients in Blantyre, Malawi.. Randomized, double-blind trial using 480 and 960 mg of CTX given to new TB patients, who were followed up until the end of the tuberculosis treatment. The primary outcome was survival. The outcome in the two groups was also compared with an unselected cohort of similar patients registered in Zomba, Malawi in 1995 and new smear-positive patients registered in the National Tuberculosis Programme in 1999. The secondary outcome was the occurrence of (opportunistic) events, especially bacterial pneumonia.. There were no statistically significant differences in mortality and bacterial pneumonia between the groups receiving the two different dosages. The case fatality rate at the end of the tuberculosis treatment was 15.4% in the 480 mg group and 14.0% in the 960 mg group. This was lower than the case fatality rate in the Zomba cohort (19.2%, P = 0.10) and lower than the case fatality rate in the national programme (21.0%, P < 0.001). CTX was well tolerated. Compliance was fair.. CTX prophylaxis may have a beneficial effect on mortality and morbidity in HIV-infected smear-positive tuberculosis patients in Malawi. The efficacy of both dosages is not significantly different. The intervention is cheap and easy to implement. These results would support implementation of CTX in this patient group until better strategies are available or evidence is convincingly presented to suggest that its benefit is marginal.

Topics: Adolescent; Adult; Antitubercular Agents; Double-Blind Method; Drug Administration Schedule; Female; HIV Infections; Humans; Malawi; Male; Middle Aged; Patient Compliance; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Neutropenia is the most frequent side effect of cotrimoxazole in sub-Saharan Africa. We estimated the incidence of haematological disorders during the first 6 months of a zidovudine-containing highly active antiretroviral therapy (HAART) regimen in sub-Saharan African adults receiving cotrimoxazole.. Prospective cohort study in Abidjan, with blood cell count measurement at baseline (HAART initiation), month 1, month 3 and month 6.. A total of 498 adults [baseline: 80% currently on cotrimoxazole prophylaxis; median CD4 count 237/mm3 [interquartile range (IQR) 181;316]; median neutrophil count 1647/mm3 (IQR 1221;2256); median haemoglobin 113 g/l (IQR 102;122)] started zidovudine (AZT)/lamivudine/efavirenz. During follow-up, 118 patients had a grade 3-4 neutropenia [(56.3/100 person-years (PY)], 23 had a grade 3-4 anaemia (9.6/100 PY) and no cases of grade 3-4 thrombocytopenia. Of the 118 patients with grade 3-4 neutropenia, 86 (73%) had to stop cotrimoxazole because neutropenia persisted, and one (<1%) had to stop AZT because of persistent neutropenia after cotrimoxazole was stopped (neutropenia-related HAART modification: 0.4/100 PY). Of the 23 patients with grade 3-4 anaemia, 11 had to stop AZT (anaemia-related HAART modification: 4.4/100 PY). In patients who stopped cotrimoxazole but not AZT, the median gain in neutrophils at 1 month was +540/mm3 (IQR +150;+896).. At baseline, most patients had a normal neutrophil count and 80% of them were already receiving cotrimoxazole. An unexpectedly high rate of grade 3-4 neutropenia occurred shortly after introduction of AZT. Almost all of the persistent severe neutropenia disappeared after cotrimoxazole was stopped. This suggests an accentuated drug interaction between the two drugs in these sub-Saharan African individuals. Grade 3-4 anaemia was much less frequent, but remained the first cause of AZT discontinuation.

Topics: Adult; Anemia; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Blood Cell Count; Blood Platelets; Cohort Studies; Cote d'Ivoire; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Neutropenia; Prospective Studies; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Child, Preschool; Diarrhea; Disinfectants; Female; HIV; HIV Infections; Housing; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Rural Population; Severity of Illness Index; Sodium Hypochlorite; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Water Purification; Water Supply

The compliance to a daily treatment for illimited duration and the factors that influence it have been rarely studied in sub-Saharian Africa.. Describe the compliance to prophylaxis with cotrimoxazole fort (one tablet per day) and its associated factors in patients infected by HIV participating in a clinical trial in Abidjan.. The tablets packed in individual blisters were provided every month, and the blisters were recuperated the following month. A global compliance ratio (GCR) was established for each patient (empty blisters at the end of the study/follow-up period during the study) and monthly compliance ratio [MCR] (empty blisters during a visit/time lapse since last visit). For each monthly visit foreseen in the protocol, a respect of the appointment ratio (RAR) was described (visits foreseen in the protocol respected that month/visits foreseen in the protocol). The association of GCR with the characteristics on inclusion was studied using logistic regression methods.. 530 adults were followed-up for a mean of 10 months. The MCR and the RAR progressed in parallel, decreasing the first 5 months and stabilizing at around 0.80 for the RAR and 0.70 for the MCR. The mean GCR was of 0.77. Three hundred and nine patients (58%) were considered as compliant (0.80

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Cote d'Ivoire; Educational Status; Female; Follow-Up Studies; HIV Infections; Humans; Logistic Models; Male; Multivariate Analysis; Occupations; Patient Compliance; Risk Factors; Severity of Illness Index; Socioeconomic Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Urban Population

Sulfamethoxazole hydroxylamine formation, in combination with long-term oxidative stress, is thought to be the cause of high rates of adverse drug reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected subjects. Therefore the goal of this study was to determine the effect of fluconazole, clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with HIV-1 infection.. HIV-1-infected subjects (CD4 + count >/=200 cells/mm 3 ) were enrolled in a 2-part (A and B), open-label drug interaction study (Adult AIDS Clinical Trial Group [AACTG] 283). In part A (n = 9), subjects received cotrimoxazole (1 tablet of 800 mg sulfamethoxazole/160 mg trimethoprim daily) alone for 2 weeks and then, in a randomly assigned order, cotrimoxazole plus either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 12) was identical to part A except that clarithromycin (500 mg twice daily) was substituted for rifabutin.. In part A, fluconazole decreased the area under the plasma concentration-time curve (AUC), percent of dose excreted in 24-hour urine, and formation clearance (CL f ) of the hydroxylamine by 37%, 53%, and 61%, respectively (paired t test, P < .05). Rifabutin increased the AUC, percent excreted, and CL f of the hydroxylamine by 55%, 45%, and 53%, respectively ( P < .05). Fluconazole plus rifabutin decreased the AUC, percent excreted, and CL f of the hydroxylamine by 21%, 37%, and 46%, respectively ( P < .05). In part B the fluconazole data were similar to those of part A. Overall, clarithromycin had no effect on hydroxylamine production.. If the exposure (AUC) to sulfamethoxazole hydroxylamine is predictive of sulfamethoxazole toxicity, then rifabutin will increase and clarithromycin plus fluconazole or rifabutin plus fluconazole will decrease the rates of adverse reactions to sulfamethoxazole in HIV-infected subjects.

Topics: Adult; Anti-Infective Agents; Area Under Curve; CD4 Lymphocyte Count; Clarithromycin; Drug Interactions; Female; Fluconazole; HIV Infections; HIV-1; Humans; Male; Middle Aged; Rifabutin; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy.. We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter.. The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years).. In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Male; Multivariate Analysis; Pneumonia, Pneumocystis; RNA, Viral; Statistics, Nonparametric; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.. Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.. Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.. Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).. Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; HIV Infections; HIV-1; HIV-2; Hospitalization; Humans; Male; Middle Aged; Odds Ratio; Placebos; Senegal; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Population

In sub-Saharan Africa, malnutrition is a major complication of HIV disease. Measuring accurately the nutritional benefits of a therapeutic intervention could be an easy-to-monitor secondary outcome.. Anthropometric data were analysed from patients participating in a placebo-controlled trial of co-trimoxazole prophylaxis in adults recruited at early stages of HIV-1 infection in Côte d'Ivoire (COTRIMO-CI ANRS 059 trial). Body mass index (BMI), arm muscle circumference (AMC) and percentage of fat mass (FM) were measured at baseline and quarterly during the follow up. Percentage of variation from the baseline value was compared between treatment groups and within the groups using Student t-test.. An improvement of all anthropometric indicators was observed in the first 3 months of follow up in both treatment groups, significant in the co-trimoxazole group (P < or = 0.0006) but not in the placebo group (P > or = 0.06). In the co-trimoxazole group, this improvement was maintained for up to 24 months for BMI (P = 0.007), 21 months for AMC (P = 0.02) and only up to 12 months for FM (P = 0.04). The placebo group had a stable anthropometric status up to the end of the trial. Differences between treatment groups were significant for up to 15 months for BMI and AMC and 12 months for FM.. As co-trimoxazole prophylaxis is now recommended in Africa as part of a minimum package of care for HIV-infected symptomatic subjects, the short-term improvement of these anthropometric indicators in adults who start co-trimoxazole prophylaxis should be considered as an effective clinical outcome.

Topics: Adult; Anti-Infective Agents; Body Mass Index; Chemoprevention; Cote d'Ivoire; Double-Blind Method; Evaluation Studies as Topic; Female; Follow-Up Studies; HIV Infections; HIV-1; HIV-2; Humans; Male; Nutritional Status; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the incidence and determinants of bacteremia, pneumonia, and sinusitis/otitis in HIV-positive people receiving cotrimoxazole (CTX) or dapsone-pyrimethamine (DP) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) within a randomized clinical trial. In total, 244 patients were randomized: 122 were assigned to CTX and 122 to DP. In the cohort, 22 bacteremia, 63 pneumonia, and 39 sinusitis/otitis cases were observed. Incidence rates of bacteremia, pneumonia, and sinusitis/otitis as well as the 2-year probability of remaining free from any bacterial infection were not significantly different between the two groups. At multivariate analysis, the risks of developing bacteremia and pneumonia were found to be independently increased by the use of a central venous catheter (hazard ratio [HR], 4.48; p <.05 and HR, 4.13; p <.01, respectively) and by hospitalization (HR, 28.82; p <.05 and HR, 10.15; p <.05, respectively). In conclusion, CTX at the dosage employed for primary PCP/TE prophylaxis does not seem to protect against bacterial infections more than second-line DP.

Topics: Adult; Animals; Anti-Infective Agents; Bacterial Infections; Dapsone; Encephalitis; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In sub-Saharan Africa where weight loss is very difficult to estimate, cross-sectional anthropometric indicators could be useful to predict human immunodeficiency virus (HIV)-associated mortality. The study objective was to look for threshold values of baseline body mass index, arm muscle circumference, and fat mass to predict the risk of death in HIV-infected adults included in a 1996-1998 trial of early cotrimoxazole chemoprophylaxis in Abidjan, Côte d'Ivoire (COTRIMO-CI-ANRS 059 trial). The authors graphically determined if consecutive anthropometric categories with the closest hazards ratios of the risk of death could be clustered to obtain a unique threshold that distinctly separated two categories. When the threshold values were determined, the authors estimated the hazards ratio of mortality of this two-category model. A significant increase of mortality was observed for a body mass index of < or =20.3 in men (hazards ratio = 2.6; 95% confidence interval (CI): 1.4, 5.0) and of < or =18.5 in women (hazards ratio = 2.2; 95% CI: 1.05, 4.5) and for a fat mass of < or =6% in men (hazards ratio = 4.6; 95% CI: 2.3, 9.4) and of < or =18% in women (hazards ratio = 2.4; 95% CI: 1.2, 4.9). No simple threshold could be identified for arm muscle circumference. In Côte d'Ivoire where chemoprophylaxis of opportunistic infections has recently been recommended to be widely initiated on clinical criteria, such thresholds may help to screen patients with higher risks of mortality.

Topics: Adult; AIDS-Related Opportunistic Infections; Anthropometry; Anti-Infective Agents; Body Mass Index; Chi-Square Distribution; Cote d'Ivoire; Cross-Sectional Studies; Female; HIV Infections; HIV-1; Humans; Male; Prognosis; Risk Factors; Skinfold Thickness; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

Topics: Adult; Antiretroviral Therapy, Highly Active; Dose-Response Relationship, Drug; Double-Blind Method; Female; HIV Infections; Humans; Male; Middle Aged; Patient Selection; Pneumonia, Pneumocystis; Racial Groups; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatment for 10 patients who had been taking one double-strength tablet of co-trimoxazole once daily for more than 1 month. Statistically significant, 47 and 23% decreases in TMP and SMX mean areas under the concentration-time curve from 0 to 24 h (AUC(0-24)), respectively, were observed after administration of rifampin. N-Acetyl-SMX profiles without and with rifampin were similar. The steady-state AUC(0-24) metabolite/parent drug ratio increased by 32% with rifampin administration. Our study shows that rifampin reduces profiles of TMP and SMX in serum of HIV-infected patients.

Topics: Adult; Anti-Infective Agents; Antibiotics, Antitubercular; Area Under Curve; Chromatography, High Pressure Liquid; Drug Interactions; Female; HIV Infections; Humans; Male; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

The relationship between the onset of adverse events to cotrimoxazole in HIV-infected patients and the subsequent development of toxoplasmosis, other AIDS-defining events and survival was studied in 592 French patients who first received cotrimoxazole during the Delta trial. Low CD4+ cell count at cotrimoxazole introduction was the only factor associated with the onset of adverse reactions. The occurrence of toxoplasmosis and first AIDS-defining events were significantly and independently linked to a low CD4+ cell count at cotrimoxazole introduction (p < 0.0001) and to previous cotrimoxazole withdrawal for adverse events (p = 0.004 and p < 0.0001, respectively), but not to previous cotrimoxazole withdrawal for reasons other than adverse events, as compared to patients who did not discontinue taking cotrimoxazole during this survey. The survival rate was significantly shorter among both patients who stopped taking cotrimoxazole for adverse events and for other reasons (p = 0.03 and p = 0.0001, respectively), as compared to patients who continued to take cotrimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Disease Progression; Double-Blind Method; Drug Eruptions; Female; France; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Survival Rate; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A multicenter open, randomized, controlled trial was conducted to determine whether primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis can be discontinued in patients infected with human immunodeficiency virus type 1 (HIV-1) whose CD4+ T cell counts have increased to >200 cells/mm3 (and who have remained at this level for at least 3 months) as a result of highly active antiretroviral therapy (HAART). Patients were randomized to either the discontinuation arm (i.e., those who discontinued prophylaxis; n=355) or to the continuation arm (n=353); the 2 arms of the study were similar in terms of demographic, clinical, and immunovirologic characteristics. During the median follow-ups of 6.4 months (discontinuation arm) and 6.1 months (continuation arm) and with a total of 419 patient-years, no patient developed P. carinii pneumonia or toxoplasmic encephalitis. The results of this study strongly indicate that primary prophylaxis for P. carinii pneumonia and toxoplasmic encephalitis can be safely discontinued in patients whose CD4+ T cell counts increase to >200 cells/mm3 during HAART.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antiprotozoal Agents; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; Paris; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anorexia; Anti-Infective Agents; Cote d'Ivoire; Deglutition Disorders; Double-Blind Method; Feeding and Eating Disorders; Female; HIV Infections; HIV-1; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Eruptions; Female; Fever; HIV Infections; HIV-1; Humans; Male; Nausea; Pneumonia, Pneumocystis; Pruritus; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this parallel treatment group, double-blind, multicenter study was to characterize the pharmacokinetics of nevirapine and lamivudine when coadministered to patients with the HIV-1 infection. This pharmacokinetic interaction study was nested within a larger Phase III clinical trial conducted to characterize the safety and efficacy of coadministered nevirapine and lamivudine. One hundred HIV-1 infected patients with CD4+ lymphocyte counts < 200 cells/mm3and who were on a background of nucleoside (zidovudine [ZDV], didanosine [ddI], zalcitabine [ddC], stavudine [d4T]) therapy were randomly assigned to be treated with either nucleoside + lamivudine + nevirapine or nucleoside + lamivudine + placebo. Each patient underwent blood sampling at defined times for the purpose of determining the concentration of nevirapine in plasma and lamivudine in serum under steady-state conditions. Each patient was also monitored closely for concomitant administration of other drugs, including ZDV, ddI, ddC, d4T and cotrimoxazole. The pharmacokinetics of nevirapine and lamivudine were characterized using nonlinear mixed-effects modeling. There were no reported serious adverse events during the 40-day pharmacokinetic study. The results of the modeling analysis revealed that nevirapine had no effect on the pharmacokinetics of lamivudine. Estimates of the apparent clearance for nevirapine (CL/F = 3.3 L/hour; 95% confidence interval [CI] 2.9 to 3.7 L/hour) and lamivudine (CL/F 27.6 L/hour; 95% CI 22 to 33.2 L/hour) were consistent with the values reported in earlier trials. However, the results also showed that concomitant administration of lamivudine with cotrimoxazole resulted in a 31% reduction in the apparent clearance of lamivudine, resulting in a 43% increase in the average steady-state lamivudine serum concentrations. These results indicate that chronic concurrent administration of cotrimoxazole with lamivudine may significantly affect the steady-state pharmacokinetics of lamivudine.

Topics: Adult; Age Factors; Anti-HIV Agents; Double-Blind Method; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Lamivudine; Male; Nevirapine; Nucleosides; Placebos; Reverse Transcriptase Inhibitors; Sex Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Côte d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection.. 843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat.. Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63.7% versus 45.8% (hazard ratio 0.57 [95% CI 0.43-0.75], p=0.0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0.51). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).. Patients who might benefit from co-trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.

Topics: Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Cause of Death; CD4 Lymphocyte Count; Cote d'Ivoire; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; HIV-1; HIV-2; Hospitalization; Humans; Incidence; Male; Severity of Illness Index; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality.. Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital.. Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group.. In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Cote d'Ivoire; Female; Follow-Up Studies; HIV Infections; HIV-1; HIV-2; Hospitalization; Humans; Incidence; Male; Middle Aged; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

This trial was conducted to study the frequency of the slow acetylator phenotype in asymptomatic HIV patients having no previous reaction to sulfa-drugs, and to compare this frequency with the frequency found in healthy controls. Results show that HIV alone is not capable of modifying the acetylator phenotype; the prevalence of slow acetylator phenotype is the same in immune competent subjects and HIV-positive patients. It is more common in HIV-positive patients with a CD4+ lymphocyte count of less than 200 mm-3.

Topics: Acetylation; Adult; Anti-Infective Agents; Drug Hypersensitivity; Female; HIV Infections; HIV Seropositivity; Humans; Kinetics; Male; Phenotype; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the influence of the dose of co-trimoxazole prophylaxis on the risk of toxoplasmosis in human immunodeficiency virus (HIV)-infected patients, we performed a nested case-control study of 32 patients with toxoplasmosis (case patients) and 64 patients without toxoplasmosis (control patients) who were matched by CD4 cell count and Toxoplasma gondii serostatus; these patients were from a cohort of 521 HIV-infected patients who underwent a diagnostic neuroimaging study between March 1993 and January 1997. Twenty-seven (84.4%) of 32 case patients and 33 (51.6%) of 64 control patients received low doses of co-trimoxazole, a finding associated with an adjusted odds ratio (OR) of 9.36 (95% confidence interval [CI], 2.05-42.75) and indicating 89% protective efficacy for high doses. Fifteen (46.9%) of 32 case patients and 16 (25%) of 64 control patients were exposed to rifampin (adjusted OR, 3.38; 95% CI, 1.08-10.61). These results indicate that high doses of co-trimoxazole appear to be more effective than low doses for lowering the risk of toxoplasmosis in HIV-infected patients and that rifampin therapy may reduce the efficacy of co-trimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Case-Control Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Encephalitis; Female; HIV Infections; Humans; Male; Rifampin; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Dapsone; Ethnicity; Female; HIV Infections; Humans; Longitudinal Studies; Male; Medical Records; Mycobacterium avium-intracellulare Infection; Naphthoquinones; New York City; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Regression Analysis; Rifabutin; Risk-Taking; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

Topics: Acetylcysteine; Adult; Anti-Infective Agents; Drug Hypersensitivity; Female; Free Radical Scavengers; HIV Infections; Humans; Incidence; Male; Middle Aged; Outcome Assessment, Health Care; Pneumonia, Pneumocystis; Primary Prevention; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent.. We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months.. Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001).. Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Female; Follow-Up Studies; HIV Infections; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid progression to AIDS (P < .001) and death (P < .001) and with a more rapid decline in CD4+ cell counts (P = .001). The median time to progression to AIDS was 14.9 months in subjects with adverse reactions to TMP-SMZ and 32.5 months in those without adverse reactions. After exclusion of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis from the case definition of AIDS, the differences in the rate of progression to AIDS between subjects with and without adverse reactions to TMP-SMZ were still highly significant (P = .004). A low CD4+ cell count at baseline and the use of antiretroviral agents before the start of prophylaxis were predictors of adverse reactions to TMP-SMZ but did not account for the difference in progression to AIDS between subjects with and without adverse reactions to TMP-SMZ. In a univariate analysis, the relative hazard of adverse reactions to TMP-SMZ for progression to AIDS was 2.54 (95% confidence interval [CI], 1.50-4.28); in a multivariate analysis, it was 2.21 (95% CI, 1.29-3.81). The relative hazards of adverse reactions to TMP-SMZ for progression to AIDS with the exclusion of PCP and toxoplasmosis, CD4+ cell counts of <50/mm3, and death were 2.16 (95% CI, 1.25-3.72), 2.37 (95% CI, 1.36-4.12), and 3.21 (95% CI, 1.80-5.72), respectively. It is unclear whether adverse reactions to TMP-SMZ induce or merely predict progression of HIV disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cohort Studies; Disease Progression; HIV Infections; HIV-1; Homosexuality, Male; Humans; Logistic Models; Male; Pneumonia, Pneumocystis; Primary Prevention; Prognosis; Prospective Studies; Survival Rate; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

I.V. pentamidine therapy in HIV-infected patients has been associated in case reports and one uncontrolled prospective series with frequent prolongation of the rate-corrected QT interval (QTc) and a high risk for potentially lethal ventricular arrhythmias, especially torsade de pointes. The aim of this study was to prospectively examine in a controlled manner the effect of I.V. pentamidine therapy on the QT interval and the incidence of ventricular arrhythmias.. Open, nonrandomized, prospective evaluation of ventricular arrhythmia incidence in HIV-infected patients receiving pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) utilizing Holter monitoring prior to and during therapy with these agents.. Staten Island University Hospital, Staten Island, NY.. Twenty-seven HIV-infected patients, of whom 16 received I.V. pentamidine and 11 received I.V. TMP-SMX.. Study patients underwent Holter monitoring prior to therapy and during the first 3 days and last 2 days of therapy with pentamidine or TMP-SMX, 12-lead ECG prior to and every 24 to 48 h, serum electrolytes prior to and on days 3, 6, 9, and 12 of therapy, and baseline transthoracic two-dimensional and Doppler echocardiography. In the pentamidine group, the results for each monitoring period were as follows (means are presented +/- SEM): pretherapy, 1.66+/-1.03 (median=0) premature ventricular complexes (PVCs) per hour, zero nonsustained ventricular tachycardia (NSVT), zero sustained ventricular tachycardia (VT); early therapy, 1.55+/-0.91 (median=0.04) PVCs per hour, two NSVT (both < or = 5 complexes), zero sustained VT; late therapy, 1.69+/-1.17 (median=0.08) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for early or late therapy as compared to pretherapy for PVCs per hour, NSVT, or sustained VT). In the TMP-SMX group, the Holter monitoring results were as follows: pretherapy, 1.36+/-1.27 (median=0) PVCs per hour, zero NSVT, zero sustained VT; early therapy, 0.71+/-0.53 (median=0.03) PVCs per hour, two NSVT, zero sustained VT; late therapy, 0.56+/-0.51 (median=0) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for pretherapy, early therapy, or late therapy with TMP-SMX as compared to pentamidine for PVCs per hour, NSVT, or VT). The QTc also did not significantly differ during therapy with pentamidine as compared to TMP-SMX. The mean QTc in the pentamidine group decreased during therapy as compared to pretherapy with the difference approaching significance for days 2, 4, and 6 with pentamidine (p<0.06).. QTc prolongation during therapy with pentamidine in HIV-infected patients is not as frequent an occurrence as has been reported previously. In the absence of QTc prolongation, pentamidine therapy was not associated with a significant increase in PVCs, NSVT, or sustained VT as compared to pretherapy recordings or as compared to therapy with TMP-SMX.

Topics: Adult; Anti-Infective Agents; Arrhythmias, Cardiac; Echocardiography; Echocardiography, Doppler; Electrocardiography; Electrocardiography, Ambulatory; Electrolytes; Female; Follow-Up Studies; Heart Ventricles; HIV Infections; Humans; Incidence; Injections, Intravenous; Male; Pentamidine; Prospective Studies; Tachycardia, Ventricular; Time Factors; Torsades de Pointes; Trimethoprim, Sulfamethoxazole Drug Combination; Ventricular Premature Complexes

Pharmacokinetic parameters of zidovudine (ZDV) were not altered in 16 patients receiving concomitant therapy with ZDV and trimethoprim-sulfamethoxazole by oral administration. ZDV areas under the concentration-time curves were (means +/- standard deviations) 1.80 +/- 0.70 and 1.69 +/- 0.64 micrograms.h/ml in the absence and presence of trimethoprim-sulfamethoxazole, respectively. ZDV clearances were 1.57 +/- 0.61 and 1.74 +/- 0.66 liters/h/kg, respectively.

Topics: Adult; Antifungal Agents; Antiviral Agents; Drug Interactions; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high frequency in human immunodeficiency virus (HIV)-infected patients. This study tested whether differences in oxidative metabolism and plasma reductive capacity correlate with sulfonamide intolerance in patients with HIV. Eighteen stable outpatients with HIV were prospectively studied. Nine patients had documented histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine did not. Urinary caffeine metabolite ratios assessed the activity of two oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8-hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8-hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The results of this pilot study extend previous observations of differences in oxidative metabolism and reductive capacity that exist within the population of HIV-infected individuals. In addition, these findings lay the groundwork for future interventional studies that could use agents to inhibit sulfonamide oxidation and increase reductive capacity in sulfonamide-intolerant patients with HIV when rechallenged with trimethoprim/sulfamethoxazole.

Topics: Adult; Anti-Infective Agents; Caffeine; Cysteine; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Oxidation-Reduction; Phosphodiesterase Inhibitors; Pilot Projects; Prospective Studies; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Eruptions; Drug Tolerance; HIV Infections; Homeopathy; Humans; Pneumonia, Pneumocystis; Prospective Studies; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A comparative open study was performed to evaluate the efficacy of single doses of ciprofloxacin (500 mg) and trimethoprim-sulfamethoxazole (TMP-SMZ; 640 mg/3,200 mg) for the treatment of culture-proven chancroid. Clinical cure or improvement was observed 7 days after treatment in 32 (76.2%) of the 42 patients who received ciprofloxacin and 21 (52.5%) of the 40 patients who received TMP-SMZ (P = .04). Cultures for one (4.5%) of 22 patients not cured with ciprofloxacin and 16 (59.3%) of 27 patients not cured with TMP-SMZ were still positive for Haemophilus ducreyi 7 days after treatment (P < .001). Although 77 (71.3%) of the 108 patients tested were seropositive for HIV-1 antibody, HIV infection and the degree of CD4+ lymphocyte depletion had no effect on clinical and bacteriologic outcome. All isolates of H. ducreyi were highly susceptible to ciprofloxacin (MIC, 0.004-0.06 mg/L). In contrast, resistance to TMP-SMZ (MIC, > or = 4/76 micrograms/mL) was observed in 48.9% of isolates (22 of 45) and was significantly associated with treatment failure. Therefore, the administration of TMP-SMZ, in single or multiple doses, is no longer indicated for the treatment of chancroid in Rwanda.

Topics: Adult; CD4 Lymphocyte Count; Chancroid; Ciprofloxacin; Drug Resistance, Microbial; Female; Follow-Up Studies; Haemophilus ducreyi; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Rwanda; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with HIV infection, but frequent adverse events limit its usefulness. Intermittent dosing and supplementation with leucovorin have been tried in attempts to improve tolerance. We evaluated these strategies in persons with advanced HIV disease.. One hundred seven patients were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3, and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily (BID); of these, 26 were randomized to leucovorin with each dose. Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week; of these, 27 were randomized to leucovorin with each dose. All patients took zidovudine concurrently.. The 24-week risk of discontinuation due to protocol-defined limiting toxicity was 24% with thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95% CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and 59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as headache and gastrointestinal distress, accounted for the observed difference in tolerance between dosing regimens. The 24-week risk of discontinuation due to protocol-defined toxicity was 33% in both the leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to 2.5). The risks of discontinuation for any reason were 53% and 47% (risk ratio 0.8; 95% CI 0.3 to 1.7).. Intermittent therapy with TMP/SMX BID thrice weekly is better tolerated than daily BID therapy. Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in AIDS, even among patients taking tablets daily.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Bone Marrow Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Proportional Hazards Models; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.

Topics: Adult; CD4 Lymphocyte Count; Disease Progression; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; HIV; HIV Core Protein p24; HIV Infections; Humans; Injections, Subcutaneous; Male; Middle Aged; Patient Compliance; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Proportional Hazards Models; Thymopentin; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Chemotherapy, Adjuvant; Double-Blind Method; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Respiratory Function Tests; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

After completion of a placebo-controlled trial of intravenous immunoglobulin (IVIG) infection prophylaxis, patients were offered open label IVIG and optional participation in a follow-up study. The purpose of the follow-up study was to evaluate the IVIG effect in original placebo recipients and longevity of IVIG benefit in original IVIG recipients. Of 212 human immunodeficiency virus-infected children on study at trial closure, 148 (67 of 98 (68%) placebo and 81 of 114 (71%) IVIG patients) received open label IVIG for a mean of 16 months. When open label IVIG was begun, 45% were receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia (43% of placebo and 47% of IVIG patients) and 54% were receiving zidovudine (55% of placebo and 53% of IVIG patients). In patients who received placebo during the original study, the rate of serious bacterial infections was significantly lower after change to open label IVIG (estimated 15.8 fewer episodes/100 patient years; 95% confidence interval, 3.2 to 28.5; P = 0.014). Similar findings were observed for minor bacterial infections (estimated 61.2 fewer/100 patient years; 95% confidence interval, 29.2 to 93.3; P < 0.001) and hospitalizations (estimated 43.7 fewer/100 patient years; 95% confidence interval, 27.7 to 59.6; P < 0.001). Decreases were observed whether or not trimethoprim-sulfamethoxazole prophylaxis was being given at the time open label IVIG was begun. In patients who received IVIG during the original study, no significant difference was seen in infections or hospitalizations after change to open label IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: AIDS-Related Opportunistic Infections; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Hospitalization; Humans; Immunoglobulins, Intravenous; Male; Pneumonia, Pneumocystis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Survival Rate; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.. An open randomized clinical trial.. HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment.. The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii.. Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Dapsone; Drug Therapy, Combination; Drug Tolerance; Female; HIV Infections; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients.. Retrospective chart review of patients followed-up to 22 May 1992.. Infectious diseases outpatient clinic of a tertiary care center in suburban New York City.. Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX.. Patients were followed clinically and with laboratory testing at approximately monthly intervals.. Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up.. Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

Topics: Adult; AIDS-Related Opportunistic Infections; Contraindications; Dapsone; Drug Eruptions; Female; Fever; Glutathione; HIV Infections; Humans; Leukopenia; Male; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients.. Prospective randomized open trial.. HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital.. A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis.. Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85).. Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol.. After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity.. At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Pyrimethamine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim and trimethoprim-sulphamethoxazole (co-trimoxazole) are often prescribed in HIV patients treated with zidovudine. The pharmacokinetics of zidovudine, after a dose of 3 mg kg-1 by constant rate intravenous infusion over 1 h were evaluated in nine HIV patients in an open, randomized, three-phase crossover study, without and with trimethoprim (150 mg) and trimethoprim-sulphamethoxazole (160 and 800 mg). The metabolic clearance of zidovudine was not significantly influenced by trimethoprim-sulphamethoxazole and trimethoprim. However, the renal clearance of zidovudine was decreased by 58 and 48%, respectively, and that of its glucuronide by 27 and 20% (P < 0.05). The fraction of the dose excreted as the parent compound fell by 47 and 39% and the metabolic ratio by 48 and 43% (P < 0.05). This kinetic drug interaction, apparently due solely to trimethoprim, may only be clinically important when hepatic glucuronidation is also impaired by liver disease or inhibited by other drugs.

Topics: Adult; Drug Interactions; Female; HIV Infections; Humans; Infusions, Intravenous; Male; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The purpose of this study was to compare the efficacy and safety of dapsone and trimethoprim/sulfamethoxazole in the primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) and having less than 200 CD4-positive cells per ml. This was a prospective, randomized, open-label study, using dapsone (100 mg p.o.) or trimethoprim/sulfamethoxazole (160 mg/800 mg p.o.) daily. Patients who developed toxicity requiring discontinuation were offered to cross over to the other study drug. They continued in the study until development of toxicity or documented PCP. Eighty-six patients were enrolled; 47 were randomized to receive dapsone and 39 to receive trimethoprim/sulfamethoxazole. Discontinuation of initial study drug occurred in 33 of the dapsone group and 25 of the trimethoprim/sulfamethoxazole group. Rash was the most common reason for discontinuation. Ten patients crossed over from dapsone to trimethoprim/sulfamethoxazole (4 successfully) and 11 patients crossed over from trimethoprim/sulfamethoxazole to dapsone (6 successfully). During 1,638 patient-months of observation (862 for dapsone and 776 for trimethoprim/sulfamethoxazole), one episode of PCP developed in each group. Both dapsone and trimethoprim/sulfamethoxazole are efficacious for the prophylaxis of PCP in HIV-infected persons with less than 200 CD4-positive cells per ml, but are each associated with significant toxicity. Development of toxicity to one drug does not invariably predict toxicity to the other.

Topics: Adult; Dapsone; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Diphenhydramine; Double-Blind Method; Drug Eruptions; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Child; Desensitization, Immunologic; Drug Hypersensitivity; Female; Follow-Up Studies; Hemophilia A; HIV Infections; Humans; Leukocyte Count; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

In an open, prospective, randomized study we compared efficacy and side effects of 8 g/d cotrimoxazole (TMP/SMX) i.v. vs. 600 mg aerosolized pentamidine. 29 of 60 planned case record forms are now evaluated. Efficacy in both groups was comparable, but side effects in the pentamidine arm were very rare (7.2% vs. 40% in the TMP/SMX group). In moderate pneumocystis carinii pneumonia aerosolized pentamidine could be the first choice therapy. Necessary conditions are to use proper inhalation systems, experience, and the treatment of relevant accompaning bacterias, which we found in 80% of pneumocystis carinii positive bronchoalveolar lavages.

Topics: Administration, Inhalation; Adult; HIV Infections; Humans; Infusions, Intravenous; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Topics: Administration, Inhalation; Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pilot Projects; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Iran; Male; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Antibacterial resistance is a growing concern worldwide, including in Mozambique. Diarrhea is an important cause of mortality in Mozambique, yet few local studies have reported on the resistance of bacterial pathogens in this context. Therefore, this study aims to characterize antibiotic susceptibility patterns of Salmonella, Shigella and Campylobacter spp. among patients with diarrhea, including those who are HIV-infected and-uninfected.. We conducted antibiotic susceptibility testing on 157 stool isolates recovered from 129 patients aged between 0 and 80 years with diarrhea, including HIV infected (n = 68) and-uninfected individuals (n = 61), assisted at two health centers in Maputo city. The isolates comprised of 99 Salmonella, 45 Shigella and 13 Campylobacter strains. The Kirby-Bauer disk diffusion method was used on Mueller-Hinton II agar for Salmonella and Shigella spp., while Mueller-Hinton II agar with 5% defibrinated sheep blood was used for Campylobacter spp. We tested six antibiotics listed on the national essential medicines list, including ciprofloxacin, erythromycin, azithromycin, trimethoprim-sulfamethoxazole, gentamicin, and tetracycline.. All isolates were resistant to at least one antibiotic. A high percentage of Salmonella spp. isolates were found to be resistant to trimethoprim-sulfamethoxazole (89.9%, n = 89), erythromycin (88.9%, n = 88) and tetracycline (76.8%, n = 76). In addition, 86.6% (n = 39) and 68.9% (n = 31) of Shigella isolates were resistant to trimethoprim-sulfamethoxazole and tetracycline, respectively. The majority of Campylobacter isolates (92.3%, n = 12) were resistant to erythromycin, azithromycin and tetracycline. Multidrug resistance (MDR) was observed in 79.8% of Salmonella spp., 76.9% of Campylobacter spp., and 57.8% of Shigella spp. Drug susceptibility profiles for Salmonella spp. and Campylobacter were similar in both HIV-1 infected and uninfected patients. However, Shigella spp. isolates obtained from patients without HIV infection were significantly more likely to be resistant to erythromycin, azithromycin or to exhibit multidrug resistance than those obtained from patients with HIV-1 infection (p < 0.05). All Shigella spp. and Campylobacter spp. isolates were susceptible to gentamicin.. Our study highlights concerning rates of antibiotic resistance and MDR among diarrheal bacterial pathogens in Mozambique. Further research is needed to understand the impact of HIV, ART therapy and immunosuppression on antibiotic resistance. Urgent interventions are essential to prevent the spread of resistant strains.

Topics: Agar; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Campylobacter; Diarrhea; Drug Resistance, Bacterial; Drug Resistance, Multiple; Erythromycin; Gentamicins; HIV Infections; Microbial Sensitivity Tests; Mozambique; Salmonella; Sheep; Shigella; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico.. A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval.. 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352).. The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Topics: Adult; Cohort Studies; HIV; HIV Infections; Humans; Mexico; Neutropenia; Pneumonia, Pneumocystis; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs).. The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated.. Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE.. Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Topics: Adult; Cicatrix; Female; HIV Infections; HLA-A Antigens; HLA-B Antigens; HLA-DRB1 Chains; Humans; Male; Middle Aged; Phenotype; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The aetiology of diarrhoea in a patient in Cuba with HIV was investigated. Although molecular diagnostics are still not used in many under-resourced settings, here traditional methods were supported by use of PCR. This approach enabled detection of a dual infection (Cystoisospora belli and Enterocytozoon bieneusi), the latter of which was not identified by microscopy with Didier's trichromic staining.

Topics: Adult; Anti-Infective Agents; Coccidiosis; Cuba; Diarrhea; Enterocytozoon; HIV Infections; Humans; Immunocompromised Host; Male; Microsporidiosis; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Sarcocystidae; Sarcoma, Kaposi; Trimethoprim, Sulfamethoxazole Drug Combination

Even though treatment failure is higher among TB and HIV infected children in a resource-limited setting, there is no prior evidence in general and in the study area in particular. Hence, this study was aimed at determining the half-life time prediction of developing first-line antiretroviral treatment failure and its risk factors among TB and HIV co-infected children.. A historical follow-up study was employed among 239 TB and HIV co-infected children from January 2010-December 2020. The data was entered into Epi data version 4.2.2 and exported to STATA 14.0 Software for analysis. The Kaplan-Meier plot was used to estimate the half-life time to develop treatment failure. The required assumption was fulfilled for each predictor variable. Additionally, those variables having a p-value ≤0.25 in the bivariable analysis were fitted into a multivariable Cox-proportional hazards regression model. P-value, < 0.05 was used to declare a significant association.. A total of 239 TB and HIV co-infected children were involved in this study. The overall half-life time to develop first treatment failure was found to be 101 months, with a total of 1027.8 years' follow-up period. The incidence rate and proportion of developing first-line treatment failure were 5.5 per 100 PPY (Person-Year) [CI (confidence interval): 3.7, 6.9] 100 PPY and 23.8% (CI; 18.8, 29.7) respectively. Factors such as hemoglobin 10 mg/dl [AHR (Adjusted Hazard Ratio): 3.2 (95% CI: 1.30, 7.73), severe acute malnutrition [AHR: 3.8 (95% CI: 1.51, 79.65), World Health Organization stage IV [AHR: 2.4 (95% CI: 1.15, 4.93)], and cotrimoxazole prophylaxis non user [AHR: 2.3 (95% CI: 1.14, 4.47)] were found to be a risk factor to develop treatment failure.. In this study, the half-life time to develop first-line treatment failure was found to be very low. In addition, the incidence was found to be very high. The presence of hemoglobin 10 mg/dl, severe acute malnutrition, World Health Organization stage, and non-use of cotrimoxazole prophylaxis were discovered to be risk factors for treatment failure. Further prospective cohort and qualitative studies should be conducted to improve the quality of care in paediatric ART clinics to reduce the incidence or burden of first line treatment failure among TB and HIV co-infected children.

Topics: Anti-Retroviral Agents; Child; Coinfection; Ethiopia; Follow-Up Studies; Half-Life; HIV Infections; Humans; Incidence; Retrospective Studies; Risk Factors; Severe Acute Malnutrition; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Pneumocystis jirovecii is a common opportunistic fungal pathogen that commonly affects immunocompromised individuals and can cause P. jirovecii pneumonia. Extrapulmonary P. jirovecii infections are extremely rare. Herein, we present a case of an HIV-positive, antiretroviral therapy-naïve patient who had extrapulmonary pneumocystosis (EPC). He presented with complaints of decreased appetite, abdominal fullness, and weight loss. Computed tomography (CT) revealed multiple low-attenuation masses in the spleen, liver, and both adrenal glands but no pulmonary involvement. A core-needle biopsy of a splenic lesion confirmed the diagnosis of EPC. The patient was initiated on intravenous trimethoprim-sulfamethoxazole (TMP-SMX) and CT-guided percutaneous catheter drainage of the splenic lesion was performed. Intravenous TMP-SMX therapy was completed in 3 weeks and intravenous pentamidine (250 mg daily) therapy was commenced. Pentamidine was completed after 3 weeks, and antiretroviral treatment (ART) was initiated with dolutegravir 50 mg and Descovy HT (emtricitabine [200 mg] and tenofovir alafenamide fumarate [25 mg]). After starting ART, the patient's clinical condition improved, and the abscesses gradually reduced. TMP-SMX is commonly used to treat EPC; however, there is no standard method of treatment. ART may become the key to EPC treatment in individuals with HIV infection.

Topics: HIV Infections; HIV Seropositivity; Humans; Male; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The level of blood filariasis parasitaemia as well as the frequency of and the relationship between cotrimoxazole prophylaxis (CTX-P), antiretroviral therapy (ART) intake and CD4 cell count among people living with human immunodeficiency virus (PLHIV) in rural areas of Gabon were being studied.. Sociodemographic data and recent biological tests of PLHIV and HIV-negative participants were collected. Loa loa and Mansonella perstans microfilaria were detected by direct microscopy examination and leucoconcentration.. Overall, 209 HIV-positive and 148 HIV-negative subjects were enrolled. The overall prevalence of microfilaria was comparable between PLHIV (19.9% [n=41/206]) and HIV-negative participants (14.8% [n=22/148]) (p=0.2). The L. loa infection rate was comparable between HIV-positive (9.2%) and HIV-negative participants (6.8%) (p=0.2), while the M. perstans infection rate was 14-fold higher among PLHIV (p<0.01). L. loa parasitaemia was 6-fold lower in PLHIV receiving CTX-P (median 150 mf/mL [interquartile range {IQR} 125-350]) than in patients without (900 [550-2225]) (p<0.01). Among subjects with a CD4 cell count <200 cells/μL, the prevalence of M. perstans was 7-fold higher than that of L. loa (20.6% vs 2.9%).. This study suggests a similar exposure to L. loa infection of PLHIV and HIV-negative patients while M. perstans is more frequently found in HIV-positive individuals, notably those with a CD4 count <200 cells/μL.

Topics: Adult; Animals; Filariasis; Gabon; HIV Infections; Humans; Loiasis; Parasitemia; Pilot Projects; Prevalence; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous adverse drug reactions (cADRs) among people living with HIV (PLWH) are common. Data on drug eruptions among PLWH in Malaysia are limited. Thus, our study aimed to determine the clinical patterns of cADRs among PLWH and the risk factors associated with severe cutaneous adverse reactions (SCAR).. A cross-sectional study was conducted among PLWH who developed cADRs presenting to our dermatology clinic from June 2020 to December 2020. The Naranjo scale was used for drug causality assessment.. A total of 78 PLWH were recruited with a male-to-female ratio of 12:1. The maculopapular eruption was the commonest type of cADRs (75.6%), followed by drug reaction with eosinophilia and systemic symptoms (DRESS) (15.4%). SCAR is defined as a potentially life-threatening, immunologically mediated, drug-induced disease, accounting for 17.9% of the cases. Most of the patients were on antiretroviral therapy (ART) (85.9%), with efavirenz + tenofovir/emtricitabine being the most common combination (80.6%). Efavirenz (51.3%) was the main culprit drug implicated, followed by trimethoprim/sulfamethoxazole (23.1%) and nevirapine (11.5%). CD4 T-cell count <100 cells/μL (. The commonest cADR seen in PLWH was maculopapular eruption, while efavirenz, trimethoprim/sulfamethoxazole, and nevirapine were the three main implicated drugs. Most of the cases had probable drug causality and were not preventable. PLWH with CD4 count <100 cells/μL were particularly at risk of developing SCAR. Overall, this study showed that immune suppression and polypharmacy as a consequence of opportunistic infection prophylaxis are important factors contributing to the increased risk of ADRs among PLWH.

Topics: Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Female; HIV; HIV Infections; Humans; Malaysia; Male; Nevirapine; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that commonly occurs in immunocompromised patients, especially those with HIV. Early diagnosis and prompt treatment are important because PJP is a potentially life-threatening infection. However, the diagnosis of PJP in the early stage can be challenging due to various factors. Furthermore, the early presentation of PJP, which includes normal chest radiograph and examination findings along with the subacute presentation of PJP in patients with HIV, makes an early diagnosis of the disease even more challenging for doctors. CASE REPORT In this case report, we present the case of a 39-year-old man who had normal chest X-ray findings during the initial stage of his presentation. Coupled with non-disclosure of HIV status, these led to a delay in PJP diagnosis. The diagnosis of PJP with underlying HIV was later supported by the patient's clinical features, initial blood investigations, and presence of high-risk sexual activity. The diagnosis was confirmed when the PJP polymerase chain reaction test from the respiratory sample was positive. He was successfully treated with oral trimethoprim-sulfamethoxazole. However, he subsequently developed rare adverse effects of drug-induced immune hemolytic anemia, which was diagnosed based on the presence of hemolytic anemia and recent exposure to a new drug. Trimethoprim-sulfamethoxazole was promptly discontinued, which resulted in symptom improvement. CONCLUSIONS This case report aims to create awareness among primary care doctors to be vigilant of the PJP diagnosis and its nonspecific presentations as well as to the rare adverse effects of medications to treat PJP.

Topics: Adult; Anemia, Hemolytic; HIV Infections; Humans; Immunocompromised Host; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Despite the scale up of antiretroviral therapy (ART), unsuppressed viral load among population taking ART in private and public health facilities is still a public health concern increasing the risk of treatment failure. Studies comprehensively assessing significant predictors of non-suppressed viral load among patients on follow up of AR in public and private health facilities are limited. The objective of the study was to identify predictors of unsuppressed viral load among adult patients taking antiretroviral therapy at selected public and private health facilities of Adama town, East shewa zone, Ethiopia.. An unmatched case-control study was conducted from April 15 /2021 to May 20/2021. A total sample size of 347 patients consisting 116 cases and 231 controls was selected from electronic database among patients who started ART from September 2015 to August 2020. Data were collected using checklist from patient medical records and analyzed by SPSS. The association of dependent and independent variables was determined using multivariate analysis with 95% confidence interval and P - value in logistic regression model to identify independent predictors.. From the total 347 participants, 140 (40.3%) of them were males and 207 (59.7%) were females. In multivariate logistic regression, CD4 count < 100 [(AOR:1.22, 95% CI: 1.4-7.3)], CD4 100-200[(AOR: 2.58 95% CI: 1.06-8.28)], Fair Adherence [(AOR: 2.44, 95% CI: 1.67-4.82)], poor adherence [(AOR: 1.11, 95% CI: 1.7-6.73)], History of Cotrimoxazole Therapy (CPT) use and not used [(AOR: 2.60, 95% CI: 1.23-5.48)] and History of drug substitution [(AOR:. 361, 95% CI: .145-.897)] were independent predictors of unsuppressed viral load with the p-value less than 0.05.. In this study, Baseline CD4, adherence, History of CPT used and history of drug substitution was predictors of unsuppressed viral load. Monitoring immunological response through scheduled CD4 tests is essential to maintain immunity of the patients preventing diseases progression. Intensive adherence support and counseling should conclusively be provided through effective implementation of ART programs by providers would enhance viral suppression ensuring the quality of care and treatment.

Topics: Adult; Case-Control Studies; Female; Follow-Up Studies; Health Facilities; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

We report here on the transmission of HIV in a cohort of breastfeeding infants enrolled in a prevention of mother to child HIV transmission (PMTCT) programme at the epicentre of the HIV pandemic. South Africa implemented option B+ for PMTCT in 2015. Between 2013 and 2018, we enrolled 1219 infants born to HIV positive women into a non-inferiority trial assessing the current cotrimoxazole prophylaxis guidelines for HIV-exposed uninfected infants. Breastfeeding mothers and infants were enrolled and followed up at one of two clinics in eThekwini, KwaZulu-Natal, until 12 months of age. During the study period, 8 infants seroconverted (<1% transmission); these were likely four birth transmissions and four breastfeeding transmissions. It is critical in the post option B era to assess the reasons for vertical transmission of HIV to enable healthcare workers and policy makers to provide strategies to mitigate future infections. This report details the possible contributors to vertical transmission in this cohort and highlights the continued strategies that should be employed to further our goal towards reaching the elimination of mother to child HIV transmission.

Topics: Breast Feeding; Child; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Human Immune deficiency Virus or Acquired Immune deficiency Syndrome (HIV/AIDS) is a pandemic affecting millions around the world. The 2020 the Joint United Nations Programme on HIV/AIDS report stated that the estimated number of people living with HIV (PLHIV) is 38 million globally by 2019. Ethiopia is among HIV high burden countries in Africa. By 2021, PLHIV in Ethiopia is estimated to be 754, 256. Globally out of 25.4 million PLHIV on ART, 41% reported virally non-suppressed. According to UNAIDS, the estimated viral non-suppression in Ethiopia is about 27%.. A hospital based retrospective cohort study was conducted among 323 patients who were enrolled to ART from July 2016 to December 2020. The medical records of study participants were selected using simple random sampling technique & data was collected using data extraction checklist. The collected data was entered and cleaned using SPSS V.25. Kaplan-Meier is used to estimate the cumulative hazard of virological failure at different time points. During bivariate analysis variables with p<0.25 were taken for Multivariate Cox regression analysis to assess predictors of virological failure & statistically significant association was declared at p<0.05 with 95% confidence interval.. The overall incidence rate of virological failure was 1.75 per 1000 months of observations. The mean survival time of virological failure was 14.80 months. Disclosure of sero-status (AHR = 0.038, 95% CI: 0.008-018), poor adherence (AHR = 4.24, 95% CI: 1.04-16), having OIs (Opportunistic infections) (AHR = 4.59, 95% CI: 1.17-18) and use of cotrimoxazole (CPT) prophylaxis (AHR = 0.13, 95% CI: 0.026-0.68) have shown statistically significant association with virological failure.. The incidence of virological failure among patients on first line ART in St. Paul's hospital is low. Disclosure of sero-status, poor adherence, having OIs and use of CPT prophylaxis were associated with virological failure. Therefore, a due attention needs to be given to these factors in order to minimize virological failure in patients on ART.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Retroviral Agents; Ethiopia; HIV Infections; Hospitals; Humans; Incidence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities.. In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurred >90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations.. Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3-2.6] for the highest, 1.6 (95% CI 1.6-1.7) for intermediate]; CD4+ cell count <350 cells/µl [aOR 1.6 (95% CI 1.1-2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1-2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3-9.4)], malnutrition [HR 1.8 (95% CI 1.1-2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0-4.9)]. Among 362 children with data, 8.6% received TB preventive treatment.. Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children.. We describe tuberculosis (TB) in children living with HIV (CLHIV) eligible for HIV treatment in South Africa to highlight opportunities to prevent TB.. We analyzed additional data from our original study of CLHIV who were 0–12 years old and due to start HIV treatment in five health facilities in Eastern Cape Province from 2012 to 2015 and assessed characteristics associated with existing and new TB.. Of 397 enrolled children, 114 (28.7%) had existing TB. Children with a higher measure of household income had higher odds of existing TB. CD4+ cell count <350 cells/µl and malnutrition were also associated with existing TB. There were 5.2 new cases of TB for every 100 child-years. New TB was 4.7 times more likely for children with delayed HIV treatment start, 1.8 times more likely for children with malnutrition and 2.3 times more likely for children who did not get cotrimoxazole. Among 362 children with data, 8.6% received treatment to prevent TB.. Among these CLHIV, existing and new TB were common. Early HIV treatment, cotrimoxazole and addressing malnutrition may prevent TB in these children.

Topics: Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Child, Preschool; HIV Infections; Humans; Incidence; Infant; Infant, Newborn; Malnutrition; Prevalence; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear.. Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively.. Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340 μg/ml. The MIC of SMX was ranging from 100 to 360 μg/ml. The MIC of TMP was ranging from 240 to 400 μg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340 μg/ml. The MIC of SMX was ranging from 340 to 360 μg/ml. The MIC of TMP was ranging from 320 to 400 μg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages.. Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection.

Topics: Acquired Immunodeficiency Syndrome; HIV Infections; Humans; Interleukin-10; Interleukin-6; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Patients who are lost to follow-up while on treatment compromise their own health and the long-term success of antiretroviral therapy (ART) programs. Besides, loss to follow-up (LTFU) increases HIV-related morbidity and mortality. Therefore, this study aimed to determine the incidence of LTFU and its predictors among adult HIV positive patients on anti-retroviral therapy at North Shoa zone public hospitals, Northeast Ethiopia.. A retrospective follow up study of 517 people living with HIV/AIDS and attending an ART clinic between 2015 and 2020 was conducted at North Shewa zone, public hospitals. Kaplan-Meier failure function together with log rank test was used to compare failure function. Multivariable Cox proportion hazards regression model was used to determine predictors of LTFU.. The incidence density rate of lost to follow up among HIV positive adult on ART was found to be 8.9 per 100 adult years observation (95%CI; 7.45, 10.68). In multivariable cox proportional regression analysis, WHO clinical stage-IV (AHR = 1.50; 95% CI: 1.08, 3.75), comorbidity disease (AHR = 0.54; 95% CI; 0.30, 0.97), body mass index less than 18kg/m2 (AHR = 1.60; 95% CI; 1.02, 2.51), cotrimoxazole preventive therapy (AHR = 1.57; 95% CI;1.09, 2.53), and a low CD4 count (AHR = 1.66; 95% CI; 1.29, 3.49) were found to be a significant predictors of lost to follow up.. The current study showed that the incidence rate of loss to ART follow-up was high. Body mass index score less than 18kg/m2, advanced WHO clinical stage, CD4<200cell/mm

Topics: Adult; Ethiopia; Follow-Up Studies; HIV Infections; Hospitals, Public; Humans; Incidence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; China; Cohort Studies; Female; HIV Infections; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Objectives To determine the performance of droplet digital polymerase chain reaction (ddPCR) assays in diagnosing Pneumocystis pneumonia (PCP), and to survey the sulfamethoxazole-trimethoprim (SMX-TMP) resistant mutations in our PCP cohort. Methods A prospective study was conducted from January 2017 to June 2018. Adult immunocompromised subjects with pneumonia were enrolled. Bronchoalveolar lavage fluid samples were obtained for standard microscopic testing and ddPCR to quantify the Pneumocystis MSG gene. DHPS and DHFR gene sequencings were performed to detect SMX-TMP resistance. Results Of 54 subjects, 12 had definite PCP, 7 had probable PCP, and 35 were non-PCP. In the PCP cohort, 10 (53%) had HIV infections. Using a cutoff value of ≥ 1.94 copies/µL, the ddPCR exhibited an overall sensitivity of 91.7% (61.5-99.8%) and specificity of 88.1% (74.4-96%). It showed a better performance when different cutoff values were used in subjects with HIV (≥ 1.80 copies/µL) and non-HIV (≥ 4.5 copies/µL). ROC curves demonstrated an AUC of 0.80 (95% CI, 0.56-1.0) for the HIV group, and 0.99 (95% CI, 0.95-1.0) for the non-HIV group. Of 16 PCP samples tested for DHPS- and DHFR-mutations, only DHPS mutations were detected (2). Most of the subjects, including those with DHPS mutations, demonstrated favorable outcomes. Conclusions The ddPCR exhibited a satisfactory diagnostic performance for PCP. Based on very limited data, the treatment outcomes of PCP did not seem to be affected by the DHPS mutations.

Topics: Adult; Dihydropteroate Synthase; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We investigated the impact of human immunodeficiency virus (HIV) infection and anti-retroviral therapy (ART) on the gut microbiota of children.. This cross-sectional study investigated the gut microbiota of children with and without HIV.. We collected fecal samples from 59 children with HIV (29 treated with ART [ART(+)] and 30 without ART [HIV(+)]) and 20 children without HIV [HIV(-)] in Vietnam. We performed quantitative RT-PCR to detect 14 representative intestinal bacteria targeting 16S/23S rRNA molecules. We also collected the blood samples for immunological analyses.. In spearman's correlation analyses, no significant correlation between the number of dominant bacteria and age was found among children in the HIV(-) group. However, the number of sub-dominant bacteria, including Streptococcus, Enterococcus, and Enterobacteriaceae, positively correlated with age in the HIV(-) group, but not in the HIV(+) group. In the HIV(+) group, Clostridium coccoides group positively associated with the CD4+ cell count and its subsets. In the ART(+) group, Staphylococcus and C. perfringens positively correlated with CD4+ cells and their subsets and negatively with activated CD8+ cells. C. coccoides group and Bacteroides fragilis group were associated with regulatory T-cell counts. In multiple linear regression analyses, ART duration was independently associated with the number of C. perfringens, and Th17 cell count with the number of Staphylococcus in the ART(+) group.. HIV infection and ART may influence sub-dominant gut bacteria, directly or indirectly, in association with immune status in children with HIV.

Topics: Age Factors; Antiretroviral Therapy, Highly Active; Bacteria; Child; Child, Preschool; Female; Gastrointestinal Microbiome; HIV Infections; Humans; Linear Models; Male; Principal Component Analysis; Staphylococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting trimethoprim-sulfamethoxazole, her diarrhea and eosinophilia improved, and she had undetectable Cystoisospora belli DNA on repeat stool quantitative polymerase chain reaction. This case highlights the importance of a thorough workup for diarrhea, including parasites, especially for immunocompromised patients. Antibiotic prophylaxis is recommended in patients with Cystoisospora belli and HIV/AIDS.

Topics: Anti-Infective Agents; Diarrhea; Eosinophilia; Female; Gastrointestinal Hemorrhage; HIV Infections; Humans; Immunocompromised Host; Isospora; Isosporiasis; Middle Aged; Sarcoma, Kaposi; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

[Background: Cotrimoxazole is the main antibiotic used in HIV-infected patients for the prophylaxis of opportunistic infections. This antibiotic is prescribed in patients receiving antiretroviral agents (ART) such as Atazanavir (ATV), a protease inhibitor used with other ART classes. The objective of this study was to compare HIV treatment failure (HIVTF) in HIV-infected patients treated concomitantly with ATV and cotrimoxazole to those of patients treated only with ATV.. This is a comparative analysis of the safety data of HIVTF available with ATV in the WHO International Pharmacovigilance database "VigiBase®". We used the SMQ (Standardized MedDRA Querie) to identify all the terms corresponding to HIVTF. We presented results as a percentage or an adjusted Reporting Odds Ratio (aROR) with a 95% confidence interval (95% CI).. A total of 116 cases of HIVTF (2.2%) were reported with ATV among the 5196 individual case safety reports (ICSR) included in the analysis. The proportion of HIV-infected patients who presented ATV treatment failure (ATVTF) was lower (2.6%, 3/116) when cotrimoxazole was concomitant (aROR was 0.5 with a 95%CI from 0.2 to 1.7). Only 10 of 273 ICSRs (3.7%) were reported from Africa concerning the use of cotrimoxazole prophylaxis concomitantly with ATV.. This study did not show a higher occurrence of ATVTF when cotrimoxazole was concomitant. These results reinforce the place of concomitant use of ATV with cotrimoxazole in the management of HIV treatment.

Topics: Africa; Anti-HIV Agents; Atazanavir Sulfate; HIV Infections; HIV Protease Inhibitors; Humans; Pharmacovigilance; Ritonavir; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Pulmonary nocardiosis is a common disease in human immunodeficiency virus (HIV)infected patients. In most cases, the disease progresses slowly. Here, we have presented a case of pulmonary nocardiosis that rapidly progressed. A 35-year-old woman with acquired immune deficiency syndrome and superior vena cava (SVC) syndrome, who was previously lost to follow-up, presented to our hospital chronic non-productive cough. Her CD4 count was 33 cells/µL (4%). Chest X-ray revealed opacity in the right upper lobe of the lung, and the results of sputum acid-fast staining were negative. Anti-tuberculosis agents were prescribed. Two weeks later, superficial vein dilatation was noted on her chest wall and the chest X-ray revealed worse findings. Chest CT showed a heterogeneous mass measuring 9.6 × 9.8 × 8.3 cm in the right lung. Further, necrotic mediastinal nodes nearly obliterated the SVC. Gram-positive beaded branching filamentous organisms were identified in the sputum by modified acid-fast staining. Hence, she was diagnosed with pulmonary nocardiosis. Culture results confirmed the presence of Nocardia beijingensis with SVC syndrome. She responded to treatment. After 2 weeks of parenteral administration, we switched her to oral trimethoprim/sulfamethoxazole, which was later followed by antiretroviral agents.

Topics: Adult; Anti-Bacterial Agents; CD4 Lymphocyte Count; Ceftriaxone; Female; HIV Infections; Humans; Lung; Nocardia; Nocardia Infections; Sputum; Superior Vena Cava Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Anti-Pneumocystis pneumonia (PCP) prophylaxis is recommended for 3 to 6 months post-transplant in HIV-negative kidney transplant recipients. For HIV-positive kidney transplant recipients, there is no definite duration of primary prophylaxis and is often prescribed life-long. The objective of this study was to determine the incidence of PCP in HIV-positive recipients who received 6 months of prophylaxis with trimethoprim-sulfamethoxazole or an alternative agent. One hundred and twenty-two HIV-positive recipients received a kidney transplant from 2001 to 2017 at Hahnemann University Hospital. Most patients received induction immunosuppression with an IL-2 receptor antagonist, with or without intravenous immunoglobulin. Only one patient received anti-thymocyte globulin. Maintenance immunosuppression included a calcineurin-inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or sirolimus), and prednisone. Mean CD4 cell count was 461 ± 127 cells/uL prior to transplant and 463 ± 229 cells/μL at 6 to 12 months after transplant. None of the recipients developed PCP after a median follow-up of 2.88 years (IQR 1.16-4.87). Based on our observation, a 6-month regimen of PCP prophylaxis may be sufficient among HIV-positive recipients, similar to those without HIV infection.

Topics: HIV Infections; Humans; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients.. From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis.. A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin.. For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Topics: Caspofungin; HIV Infections; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Retroviral Agents; HIV Infections; Humans; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets.. We conducted a cross-sectional household survey.. Consenting adults and children in the household were eligible to participate in Zimbabwe Population-based HIV Impact Assessment (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. Viral load suppression (VLS) was defined as HIV RNA <1000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15-64 years.. We enrolled 11,098 men and 14,033 women aged 15-64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9 to 78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1 to 89.7) were receiving antiretroviral therapy (ART), and of these people, 85.3% (95% CI: 83.4 to 87.1) had VLS. Male sex age 15-34 years and having 1 or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS.. Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged <35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets.

Topics: Adolescent; Adult; Anti-Retroviral Agents; Child; Cross-Sectional Studies; Female; Health Knowledge, Attitudes, Practice; HIV Infections; Humans; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult; Zimbabwe

Topics: Adult; Africa South of the Sahara; Anti-Inflammatory Agents; HIV; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gastrointestinal Microbiome; HIV; HIV Infections; Humans; Infant; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined.. We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants.. Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2-1.2] and 6-month mean, 0.85 [95% CI, .1-1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, -0.11 [95% CI, -.15 to -.077]), functional taxonomic (mean, -0.050 [95% CI, -.084 to -.017]), and resistance gene (mean, -0.13 [95% CI, -.17 to -.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure.. Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance.

Topics: Female; Gastrointestinal Microbiome; HIV; HIV Infections; Humans; Infant; Pregnancy; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cryptococcosis; Cryptococcus; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Antimicrobials have become a mainstay of healthcare in the past century due to their activity against pathogens. More recently, it has become clear that they can also affect health via their impact on the microbiota and inflammation. This may explain some of their clinical benefits despite global increases in antimicrobial resistance (AMR) and reduced antimicrobial effectiveness. We showed in a randomized controlled trial of stopping versus continuing cotrimoxazole prophylaxis among HIV-positive Zimbabwean children taking antiretroviral therapy (ART), that continuation of cotrimoxazole persistently suppressed gut-resident viridans group streptococcal species (VGS) that were associated with intestinal inflammation. In this addendum, we provide a broader overview of how antibiotics can shape the microbiota and use high read-depth whole metagenome sequencing data from our published study to investigate whether (i) the impact of cotrimoxazole on gut VGS and (ii) VGS associated inflammation, is attributable to strain-level variability. We focus on

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Antibiotic Prophylaxis; Child; Feces; Gastrointestinal Microbiome; HIV Infections; Humans; Inflammation; Intestines; Species Specificity; Streptococcus salivarius; Trimethoprim, Sulfamethoxazole Drug Combination; Viridans Streptococci; Zimbabwe

To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan.. From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized.. Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

Topics: Adult; Anti-Bacterial Agents; Female; HIV Infections; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Nasal Mucosa; Prevalence; Risk Factors; Staphylococcal Infections; Substance Abuse, Intravenous; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTX-induced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Hypersensitivity Syndrome; Female; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; HIV Infections; HLA Antigens; Humans; Male; Middle Aged; Phenotype; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stevens-Johnson Syndrome; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Asthma; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Diagnosis, Differential; DNA, Bacterial; Emtricitabine; Glucocorticoids; HIV Infections; Humans; Lung; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Oxygen Inhalation Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumonia, Viral; Prednisolone; Raltegravir Potassium; Real-Time Polymerase Chain Reaction; RNA, Viral; SARS-CoV-2; Tenofovir; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Complete follow-up of human immunodeficiency virus (HIV)-exposed infants (HEI) is crucial for a successful prevention of mother-to-child HIV transmission. This study analyzed the HEI follow-up and factors associated with loss to follow-up (LTFU) in southern Mozambique.. This retrospective cohort study used the data of HEI enrolled between June 2017 and June 2018, followed-up for 18 months. The outcomes were the proportion of infants with completed follow-up and a definitive diagnosis, and the presence of clinical events. Kaplan-Meier survival analysis was used to calculate the cumulative probability of LTFU and of clinical events. Factors associated with LTFU and clinical events were analyzed using Cox regression to calculate the hazard ratio (HR) and adjusted HR (AHR), with a 95% confidence interval (CI) and a significance cutoff of p<0.05.. 1413 infants were enrolled (49% males) at a median age of 32 days (IQR 31-41); the median follow-up time was 12 months (IQR 8.2-14.2); 1129 (80%) completed follow-up and had a definitive diagnosis, 58 (4%) were HIV-positive, 225 (16%) were LTFU; 266 (19%) presented a clinical event. Factors associated with LTFU were: age >2 months at entry (AHR, 1.58; 95% CI, 1.12-2.23), non-exclusive breastfeeding (AHR, 1.44; 95% CI, 1.01-2.06), poor cotrimoxazole adherence (AHR, 3.42; 95% CI, 1.59-7.35), and clinical events (AHR, 0.51; 95% CI, 0.34-0.77). Factors associated with clinical events were: malnutrition (AHR, 10.06; 95% CI, 5.92-17.09), non-exclusive breastfeeding (AHR, 1.98; 95% CI, 1.34-2.93), no nevirapine prophylaxis (AHR, 1.67; 95% CI, 1.18-2.36), and poor cotrimoxazole adherence (AHR, 2.62; 95% CI, 1.10-6.22).. The high rate of HEI LTFU, associated with delayed linkage to postnatal care, poor prophylaxis adherence, non-exclusive breastfeeding, indicates the need to design a differentiated service delivery model that is tailored to the mothers' and infants' specific needs.

Topics: Anti-Retroviral Agents; Breast Feeding; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Lost to Follow-Up; Male; Medication Adherence; Missed Diagnosis; Mozambique; Nevirapine; Proportional Hazards Models; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Although WHO recommends cotrimoxazole (CTX) discontinuation among HIV patients who have undergone immune recovery and are living in areas of low prevalence of malaria, some countries including Uganda recommend CTX discontinuation despite having a high malaria burden. We estimated the prevalence and factors associated with malaria parasitaemia among adults living with HIV attending hospital outpatient clinic before and after discontinuation of CTX prophylaxis.. Between March and April 2019, 599 participants aged 18 years and above, and attending Kitgum hospital HIV clinic in Uganda were enrolled in a cross study. A standardized questionnaire was administered and physical examination conducted. A finger-prick blood sample was collected for identification of malaria parasites by microscopy. The prevalence of parasitaemia was estimated and compared among participants on and those who had discontinued CTX prophylaxis, and factors associated with malaria parasitaemia assessed.. Of the enrolled participants, 27 (4.5%) had malaria parasites and 452 (75.5%) had stopped CTX prophylaxis. Prevalence of malaria parasitaemia was significantly higher in participants who had stopped CTX prophylaxis (5.5% versus 1.4% p = 0.03) and increased with increasing duration since the discontinuation of prophylaxis. Compared to participants taking CTX, those who discontinued prophylaxis for 3-5 months and >5 months were more likely to have malaria parasites (adjusted prevalence ratio (aPR) = 1.64, 95% CI 0.37-7.29, p = 0.51, and aPR = 6.06, 95% CI 1.34-27.3, P = 0.02). Low CD4 count (< 250cells/mm3) was also associated with increased risk of having parasites (aPR = 4.31, 95% CI 2.13-8.73, p <0.001).. People from malaria endemic settings living with HIV have a higher prevalence of malaria parasitaemia following discontinuation of CTX compared to those still on prophylaxis. The risk increased with increasing duration since discontinuation of the prophylaxis. HIV patients should not discontinue CTX prophylaxis in areas of Uganda where the burden of malaria remains high. Other proven malaria control interventions may also be encouraged in HIV patients following discontinuation of CTX prophylaxis.

Topics: Adult; Antimalarials; Cross-Sectional Studies; Female; HIV Infections; Humans; Malaria; Male; Middle Aged; Parasitemia; Plasmodium; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited.. This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia.. A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis.. Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4-15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05-4.9) and gender (AOR: 2.5; 95% CI: 1.09-5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3-36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant.. The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.

Topics: Adult; Anti-HIV Agents; Antibiotic Prophylaxis; Carrier State; Case-Control Studies; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Ethiopia; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Nasopharynx; Pneumococcal Infections; Sex Characteristics; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Topics: Adolescent; Adult; Aftercare; Anti-Retroviral Agents; Antitubercular Agents; Chemoprevention; Cohort Studies; Coinfection; Delivery of Health Care; Drug Resistance, Multiple, Bacterial; Female; Health Plan Implementation; HIV Infections; Humans; Leprosy; Male; Middle Aged; Models, Organizational; Mycobacterium leprae; Mycobacterium tuberculosis; Patient Care Team; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Uganda; Young Adult

Intestinal parasites infections are endemic in Gabon. Nevertheless, they are rarely described in people living with HIV (PLHIV).. The frequency of intestinal parasite infection was estimated and compared between HIV-positive and HIV uninfected individuals in Gabon; factors associated with intestinal parasites were also analysed.. Using a cross-sectional study design sociodemographic data, life style habits, antiretroviral therapy, cotrimoxazole use and CD4 cell count were recorded.. Stool samples from participants living in Koulamoutou and Oyem were analysed using microscopy. Chi-squared or fisher's exact tests and logistic regression were performed.. Among participants (n=332), female gender was predominant (73.7%; n=135/183) and the median age was 45 [33-57] years old. Among 183 samples, 53.6% (n = 98/183) were infected by intestinal parasites. The proportion was higher (72.1%) in HIV negative participants compared to PLHIV (42.6%) (p <0.01). PLHIV were more frequently poly-infected. Infection was frequent in patients using external toilets and tap water (>70.0%).. Prevalence of intestinal parasites is higher in seronegative participants but polyparasitism is more frequent in PLHIV. Strategies are focused on HIV negative population, but this study shows the importance of sensitization for PLHIV to improve their quality of life.

Topics: Adolescent; Adult; Antiretroviral Therapy, Highly Active; Carrier State; Coinfection; Cross-Sectional Studies; Feces; Female; Gabon; HIV Infections; Humans; Intestinal Diseases, Parasitic; Male; Middle Aged; Prevalence; Quality of Life; Risk Factors; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole is well known to cause intra-hepatic cholestasis which in rare instances can be prolonged and lead to vanishing bile duct syndrome. The risk regarding the potential for cross-reactivity between structurally related molecules such as dapsone and trimethoprim/sulfamethoxazole in causing hepatotoxicity is scarce. Herein, we report a case of vanishing bile duct syndrome following dapsone use in a patient with HIV infection and a recent history of trimethoprim/sulfamethoxazole-induced cholestasis. The patient had severe and protracted cholestasis during 2 years of follow-up and eventually died of liver failure.

Topics: Anti-Infective Agents; Cholestasis, Intrahepatic; Dapsone; Drug Interactions; Drug Therapy, Combination; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Intestinal parasitic infections are among the most common communicable diseases worldwide, particularly in developing countries. Human immunodeficiency virus (HIV) causes dysregulation of the immune system through the depletion of CD4+ T lymphocytes which gives rise to opportunistic infections.. A cross-sectional study was conducted from January to October 2018. Stool and blood samples were collected from participants aged 1 to 19. Stool samples were analyzed for intestinal parasites. Blood samples were analyzed for HIV and CD4 + T cell counts.. Out of 214 children enrolled, 119 (55.6%) were HIV infected and 95 (44.4%) were HIV non-infected. All infected children were on antiretroviral treatment (ART). The prevalence of intestinal parasites was 20.2% in HIV infected and 15.8% in non-infected children. Among the 119 HIV infected children, 33 (27.7%) of them had a CD4+ T cell count less than 500 cells/mm3, and amongst them 5.9% had CD4+ T cell count less than 200 cells/mm3. Among HIV infected children, Cryptosporidium spp. was frequently detected, 7/119 (5.9%), followed by Giardia lamblia 5/119 (4.2%) then Blastocystis hominis 3/119 (2.5%) and Entamoeba coli 3/119 (2.5%). Participants on ART and prophylactic co-trimoxazole for >10 years had little or no parasite infestation.. Although ART treatment in combination with prophylactic co-trimoxazole reduces the risk of parasitic infection, 20.2% of HIV infected children harbored intestinal parasites including Cryptosporidium spp. Stool analysis may be routinely carried out in order to treat detected cases of opportunistic parasites and such improve more on the life quality of HIV infected children.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Blastocystis hominis; Cameroon; Candida; Child; Child, Preschool; Cross-Sectional Studies; Cryptosporidium; Entamoeba; Feces; Female; Giardia lamblia; HIV Infections; Humans; Infant; Intestinal Diseases, Parasitic; Male; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculosis (TB) is among the world's top public health challenges and the leading killer of people with HIV, yet is a treatable disease. This study aimed to assess, in a real-world setting, the implementation of antiretroviral therapy (ART) and Cotrimoxazole preventive therapy (CPT) policy, specific interventions proven to benefit patients in HIV-associated TB care.. This retrospective cohort study was conducted in Botswana in the Serowe/Palapye district, a largely urban district with a high burden of HIV-associated TB with a high case fatality, at Segkoma and Palapye hospitals and their feeder clinics. Between 1 January 2013 and 31 December 2013, confirmed HIV-positive patients aged ≥15 years with a confirmed TB diagnosis and medical record available were included in the analysis. The Kaplan-Meier method was used to compare time to death for the group of patients on ART and the group of patients not on ART during TB treatment. Cox proportional hazard regression was undertaken to identify predictors of mortality.. Of the 300 patients included in the study, 217 (72%) were ART experienced at TB diagnosis. Of these, 86 (40%) had TB within 3 months following ART initiation. Of the 83 (28%) patients who were ART-naïve at TB diagnosis, 40 (48%) were commenced on ART during TB treatment, with 24 (60%) patients commencing within 4 weeks following TB treatment initiation. The overall ART uptake was 84%, while cotrimoxazole preventive therapy uptake was 100%. There were 45 deaths (15%), ART-experienced patients during TB treatment accounted for 30 deaths (30/257; 14%), while those who were not ART-experienced during TB treatment accounted for 15 deaths (15/43; 35%). There was a significant difference in survival time between patients with no ART use during TB treatment and those with ART use during TB treatment (log rank p < 0.001). Patients with no ART use during TB treatment were more likely to die within the first 2 months.. The implementation of CPT policy is a substantial success. Strengthening the implementation of ART policy could improve survival among HIV-associated TB patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Botswana; Coinfection; Female; Guideline Adherence; Health Plan Implementation; HIV; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

This study aimed to assess the evolution of body mass index (BMI) of HIV-positive adults on second-line antiretroviral therapy (ART) over time and factors affecting it in north-west Ethiopia.. An institution-based retrospective follow-up study was conducted using data extracted from 1016 patient cards from February 2008 to February 2016.. Eight referral hospitals from Amhara region, Ethiopia were included.. HIV patients who started second-line ART.. Change in BMI since starting second-line ART.. Five hundred and thirty-eight (52.95%) participants were males and the median age of the participants was 33 years (IQR: 28; 39). The median follow-up time was 18 months (IQR: 5.2; 32.2). The average change of BMI showed linear increase over time. The amount of BMI increment or decrement according to each variable was shown as β coefficients. Treatment duration (β=0.013, 95% CI 0.004 to 0.022), isoniazid prophylaxis (β=0.87, 95% CI 0.32 to 1.42), cotrimoxazole prophylaxis (β=0.63, 95% CI 0.08 to 1.19), ambulatory functional status (β=-1.16, 95% CI -1.95 to 1.31), bedridden functional status (β=-1.83, 95% CI -2.47 to 1.21), WHO stage III (β=-0.42, 95% CI -0.65 to 0.20), WHO stage IV (β=-0.62, 95% CI -1.02 to 0.22), CD4 count (β=0.001, 95% CI 0.0008 to 0.0015), and time interaction of variables like tertiary educational status (β=0.02, 95% CI 0.01 to 0.04), ambulatory functional status (β=0.03, 95% CI 0.01 to 0.05) and WHO stages III (β=0.01, 95% CI 0.007 to 0.02) were found to be significant predictors.. The BMI of patients has shown linear increment over the treatment time. Factors affecting it have been identified but its effect on cardiovascular disease needs further study.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; CD4 Lymphocyte Count; Coinfection; Ethiopia; Female; Follow-Up Studies; HIV Infections; Humans; Isoniazid; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Gain

Following the introduction of option B+ in 2013, and with the perspective of eliminating mother-to-child transmission of HIV by 2025, Cambodia has implemented an integrated active case management (IACM) approach since 2014 to improve the notification and follow-up of all HIV-infected cases including pregnant women, and to ensure access to and use of the full prevention of mother-to-child transmission (PMTCT) service package by HIV-infected pregnant women and their HIV-exposed infants. This study aimed to analyse PMTCT cascade data in 15 operational districts (ODs) implementing the IACM approach in Cambodia.. We analysed PMTCT cohort data from 15 ODs implementing IACM approach between 1 January 2014 and 31 December 2016. We measured key indicators along the PMTCT cascade and compared them to available (cross-sectional) PMTCT indicators during the 2011 to 2013 period.. During the period 2014 to 2016, among 938 identified HIV-infected pregnant women, 308 (32.8%) were tested HIV positive during their pregnancy, 9 (1.0%) during labour, while the remaining 621 (66.2%) were women on antiretroviral therapy (ART) who became pregnant. During the study period, 867 (92.4%) of the 938 women received ART during pregnancy and labour. Subsequently, 456 (85.6%) of the 533 HEI born and alive during the study period received 6-week antiretroviral (ARV) prophylaxis, 390 (76.6%) and 396 (77.8%) of the 509 infants aged six weeks or older received cotrimoxazole prophylaxis and HIV-DNA PCR test respectively. Among the 396 HEI who received HIV-DNA PCR test, 7 (1.8%) were found HIV positive. The comparison with cross-sectional PMTCT indicator obtained during the previous 2011 to 2013 period in the same 15 ODs, showed a significant increase in ARV uptake among HIV-infected pregnant women (from 72.3% to 92.4%), in cotrimoxazole uptake (from 41.6% to 73.2%), and in HIV-DNA PCR testing coverage among HEI (from 41.2% to 74.3%).. The implementation of option B+ and IACM may have contributed to the improvement of the PMTCT cascade in Cambodia. However, some gaps in accessing PMTCT services along the HIV cascade persist and need to be addressed.

Topics: Adolescent; Adult; Anti-HIV Agents; Cambodia; Case Management; Cohort Studies; Cross-Sectional Studies; Delivery of Health Care; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Female; HIV Infections; Humans; Infant; Morbidity; Pregnancy; Pregnancy Complications, Infectious; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART).. We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death.. A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015-2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09-1.28]), lower height-for-age z score (OR, 1.15 for less than -3 vs greater than -2 [95% CI, 1.08-1.22]), anemia (OR, 1.08 [95% CI, 1.02-1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18-1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17-9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77-1.34]).. Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency.

Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Drug Administration Schedule; Female; HIV Infections; Humans; Infant; Male; Risk Factors; Severity of Illness Index; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

We present the case of a human immunodeficiency virus (HIV)-infected patient who arrived at our emergency department with fever, headache and exertional dyspnea. Throughout their stay, a chest x-ray was taken and a rounded opacity in his left lung was observed. CT images showed same abnormality and also ground glass opacities were seen. Symptoms and images strongly suggested a pulmonary infection due to pneumocystis jirovecii, however a presence of a round lesion should always lead to neoplasia being suspected. We empirically started treatment based on trimethoprim and sulfamethoxazole. Once available, flexible bronchoscopy and bronchoalveolar lavage was performed and stained preparations from his respiratory specimens confirmed the diagnosis of pulmonary pneumocystis infection. Finally, after 4 days of antibiotic therapy, an important clinical improvement was documented; a new chest x-ray was performed and the previous rounded opacity was absent. This finding strongly suggested a case of round pneumonia.

Topics: Adult; Antifungal Agents; Diagnosis, Differential; Emergency Service, Hospital; HIV Infections; Humans; Lung; Lung Neoplasms; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%. But the effectiveness of adjunctive corticosteroids with trimethoprim-sulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP.. We did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights.. 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO. The adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.

Topics: Adrenal Cortex Hormones; Adult; Aged; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) remains a debilitating cause of death among HIV-infected patients. The combination trimethoprim/sulfamethoxazole (SXT) is the most effective anti-Pneumocystis treatment and prophylaxis. However, long-term use of this combination has raised alarms about the emergence of resistant organisms. This study was performed to investigate mutations in the dihydropteroate synthase (DHPS) gene and their clinical consequences in HIV-infected patients with PCP.. A total of 76 clinically suspected cases of PCP among HIV-seropositive adult patients from March 2014 to March 2017 were included. Clinical samples (bronchoalveolar lavage fluid and sputum) were investigated for the detection of Pneumocystis jirovecii using both microscopy and nested PCR. DHPS genotyping and mutational analyses were performed and the data were correlated with clinical characteristics.. This study suggests that the emergence of a mutant P. jirovecii genotype is probably associated with drug resistance and mortality. The data also suggest that DHPS mutational analyses should be performed in HIV-seropositive patients to avoid treatment failure and death due to PCP. However, the role of underlying disease severity and co-morbidities should not be underestimated.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Coinfection; Dihydropteroate Synthase; DNA Mutational Analysis; Drug Resistance, Fungal; Drug Resistance, Multiple, Bacterial; Female; Genotype; HIV Infections; Humans; India; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumocystis Infections; Polymerase Chain Reaction; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Diagnosis, Differential; Dyspnea; HIV Infections; Humans; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalaemia is a potentially life-threatening condition frequently encountered in hospitalised patients. Among the many causes of hyperkalaemia, drugs have often been implicated. In the South African context, with the high burden of HIV, there is an increased incidence of opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), and consequently many patients receive high doses of trimethoprim-sulfamethoxazole. A lesser-known side-effect of the trimethoprim component of this combination antibiotic is hyperkalaemia. We report a case in which life-threatening hyperkalaemia developed after institution of high-dose co-trimoxazole for PJP.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Female; HIV Infections; Humans; Hyperkalemia; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Despite high antiretroviral (ARV) treatment coverage among pregnant women for prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in Zimbabwe, the MTCT rate is still high. Therefore in 2016, the country adopted World Health Organization recommendations of stratifying pregnant women into "High" or"Low" MTCT risk for subsequent provision of HIV exposed infant (HEI) with appropriate follow-up care according to risk status.. The study sought to ascertain, among pregnant women who delivered in clinics of Harare in August 2017: the extent to which high risk MTCT pregnancies were identified at time of delivery; and whether their newborns were initiated on appropriate ARV prophylaxis, cotrimoxazole prophylaxis, subjected to early HIV diagnostic testing and initiated on ARV treatment.. Cross-sectional study using review of records of routinely collected program data.. Of the 1,786 pregnant women who delivered in the selected clinics, HIV status at the time of delivery was known for 1,756 (98%) of whom 197 (11%) were HIV seropositive. Only 19 (10%) could be classified as "high risk" for MTCT and the remaining 90% lacked adequate information to classify them into high or low risk for MTCT due to missing data. Of the 197 live births, only two (1%) infants had a nucleic-acid test (NAT) at birth and 32 (16%) infants had NAT at 6 weeks. Of all 197 infants, 183 (93%) were initiated on single ARV prophylaxis (Nevirapine), 15 (7%) infants' ARV prophylaxis status was not documented and one infant got dual ARV prophylaxis (Nevirapine+Zidovudine).. There was paucity of data requisite for MTCT risk stratification due to poor recording of data; "high risk" women were missed in the few circumstances where sufficient data were available. Thus "high risk" HEI are deprived of dual ARV prophylaxis and priority HIV NAT at birth and onwards which they require for PMTCT. Health workers need urgent training, mentorship and supportive supervision to master data management and perform MTCT risk stratification satisfactorily.

Topics: Adolescent; Adult; Anti-Retroviral Agents; Antibiotic Prophylaxis; Cross-Sectional Studies; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Mass Screening; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zimbabwe

The N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies.. The aim of this study was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians.. Phenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping. The NAT2 gene was amplified by PCR. Gene sequencing used ABI 3730 and Haploview 4.2 for haplotype reconstruction. Genotype-phenotype analyses used the χ P-value and odds ratio with a 95% confidence interval.. Self-reported sulphonamide hypersensitivity showed a prevalence of 3.1 and 12.4% in HIV-positive and HIV-negative Nigerians, respectively. NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G and 857G>A were not significantly different between both groups (odds ratio=0.87; 95% confidence interval: 0.54-1.38, P=0.55). Nine haplotypes: NAT2*4, NAT2*12A, NAT2*13A, NAT2*5B, NAT2*6A, NAT2*7B, NAT2*5C, NAT2*14B and NAT2*14A had frequencies more than 1%, whereas NAT2*12B had 1.1% in the HIV-positive and 0.4% in the HIV-negative group. Overall, slow acetylator haplotypes made up 68%. The NAT2*12 signature single-nucleotide polymorphism was in high linkage disequilibrium with signature single-nucleotide polymorphism for NAT2*13 (D'=0.97, r=0.61) and NAT2*5 (D'=0.98, r=0.64). Genotype-phenotype association analysis showed haplotypes NAT2*13A, NAT2*5C, NAT2*7B and NAT2*14A to be associated strongly with the slow metabolic phenotype (P=0.002, 0.029, 0.032 and 0.050, respectively). Computational phenotypes were similar, with 30.9, 66 and 3.1% for slow, intermediate and rapid acetylators, respectively, among HIV-positive Nigerians and 31.2, 66.3 and 2.5% among the HIV-negative group. Overall, slow phenotypes made up 31%.. NAT2 haplotype frequencies are similar in Nigerians, irrespective of HIV status, but genotype-phenotype discordances exist.

Topics: Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genetic Association Studies; Haplotypes; HIV; HIV Infections; Humans; Male; Middle Aged; Nigeria; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Fibrosing interstitial lung disease is the poor prognostic non-infectious lung disease by unknown etiology. Here, we present one case developing interstitial pneumonia with fibrosis after treatment of pneumocystis pneumonia (PCP) in newly diagnosed HIV-1 infected case.. A previously healthy 63-year old male was referred to our institute because of protracted dyspnea on effort in 2 weeks after pneumocystis pneumonia treatment. At referral, arterial blood oxygen pressure was within normal range (93.5 mmHg) at rest, but decreased rapidly 30 s after a slow walk (44.5 mmHg). Respiratory function tests showed severe restrictive ventilator impairment (vital capacity = 36.5%; forced expiratory volume in 1 s = 107.4%). Chest computed tomography showed severe fibrotic changes at bilateral basal parts and diffuse fibrotic changes in which PCP lesions were seen initially in previous images although β-D glucan was not elevated and P. jirovecii was not detected in saliva at referral. Other etiologies of fibrotic IP including infectious and/or autoimmune diseases were excluded by serology. Fibrotic lesion did not expand thereafter although it had not responded to the high-dose corticosteroid therapy.. We report the first case of fibrosing interstitial lung disease triggered by HIV-related PCP.

Topics: AIDS-Related Opportunistic Infections; beta-Glucans; Forced Expiratory Volume; HIV Infections; Humans; Immunocompromised Host; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear.. Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.. A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.. CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

Topics: Adult; Anti-HIV Agents; Anti-Retroviral Agents; Asia; Cohort Studies; Female; HIV Infections; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Viral Load

Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy.. We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches.. We compared a group of patients treated with cotrimoxazole and receiving an ATV-based regimen to controls. This historical cohort analysis used data from Dat'AIDS in HIV-infected patients who had at least two lowest plasma concentrations (C-trough) of ATV during their outpatient follow-up. Likewise, we used the international pharmacovigilance data from VigiBase to evaluate the notifications of hyperbilirubinemia reported with ATV.. In the TDM analysis, the two groups of patients (treated with cotrimoxazole and controls) were almost homogeneous concerning the main baseline features. After at least six months of ATVbased regimen, there was no significant difference in the safety threshold of the ATV C-trough [with an adjusted odds ratio (aOR) of 1.4 (95% CI: 0.5 - 4.4)] compared to controls. We observed similar results with the efficacy thresholds of ATV C-trough. Regarding the PV analysis, there was no difference in hyperbilirubinemia occurring with ATV when cotrimoxazole was concomitant, with an adjusted reporting odds ratio (aROR) of 0.9 (95% CI: 0.6 to 1.2).. This study showed a relevant concomitant use between Cotrimoxazole and ATV based on TDM and PV approaches.

Topics: Adult; Aged; Atazanavir Sulfate; Drug Monitoring; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pharmacovigilance; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical characteristics of Pneumocystis jirovecii pneumonia (PCP) in patients with immunodeficiency virus (HIV) infection (HIV-PCP) differ from those in patients without HIV infection (non-HIV-PCP). We analyzed 31 adult HIV-PCP cases and 44 non-HIV-PCP cases between 2008 and 2018. The symptomatic period before the diagnosis was shorter in non-HIV-PCP (5 [3-8] days vs. 29 [14-55] days, P < 0.001) and the overall survival rate was lower in the non-HIV-PCP group (P = 0.022). Serum β-D glucan positivity (72.7% vs. 93.5%, P = 0.034) and Grocott stain positivity for Pneumocystis jirovecii in the bronchoalveolar lavage fluid (4.3% vs. 73.3%, P < 0.001) were significantly lower in the non-HIV-PCP group. This difficulty in laboratory diagnosis possibly resulted in the administration of concurrent antibiotics such as quinolones and macrolides (56.8% vs. 19.4% P = 0.002) in the non-HIV-PCP group. The adverse effects due to trimethoprim-sulfamethoxazole were more frequently observed in HIV-PCP (86.2% vs. 35.3%, P < 0.001). The duration of discontinuation of trimethoprim-sulfamethoxazole was 11 [8-14.5] days in HIV-PCP cases. Co-administration of adjunctive corticosteroid therapy did not mitigate hypersensitivity to trimethoprim-sulfamethoxazole. Our analysis indicated that the characteristics of PCP in patients with or without HIV was quite different. HIV-positive patients with PCP should be monitored closely to avoid adverse effects due to trimethoprim-sulfamethoxazole. Because positivity polymerase chain reaction test for P. jirovecii remained high (91.7%), it is suggested that bronchofiberscopy is warranted for diagnosis of PCP in HIV-negative patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; HIV Infections; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculosis (TB) and HIV co-infection challenges treatment and worsens the outcome of TB treatment. This study aimed to assess the outcome of TB treatment and factors facilitating treatment success among people living with HIV/AIDS in Fako Division of the South West Region of Cameroon.. A hospital-based retrospective cohort study was conducted by manually reviewing medical records of HIV/TB co-infected patients from January 2010 to September 2017. A structured data collection form was used to review the medical records of HIV patients co-infected with TB aged 10 years and older. Patients with incomplete files were dropped from the study. Treatment success was defined as the sum of patients who were declared cured and those who had completed treatment, as per the World Health Organization's recommendations. Data were analyzed using Statistical Package for Social Sciences version 21. Bivariate and multivariate logistic regression model was carried out to identify factors facilitating successful TB treatment outcome. Significance was obtained through adjusted odds ratio with its 95% confidence interval and a p<0.05.. A total of 2,986 files were reviewed but 2,928 (98.1%) were retained. Out of the 2,928 medical files of adult TB patients reviewed, 1,041 (35.6%, [95% CI 33.8%-37.3%]) were HIV/TB co-infected. The 1,041 co-infected patients had a mean age of 37.07 (SD of10.02) years and 56.3% were females. The treatment outcome of TB patients were 795(76.4%) cured, 23(2.2%) treatment completed, 99(9.5%) were lost to follow-up, 16 (1.5%) failed, 72(6.9%) died and 36(3.5%) transferred out. A successful treatment outcome was achieved in 818(78.6%,[95% CI: 76.0%-81.0%]) patients. Being a female [COR 1.61, 95% CI: 1.19-2.17, p = 0.002], receiving TB treatment in 2014 [COR 2.00, 95% CI: 1.11-3.60, p = 0.021] and 2015 [COR 2.50, 95% CI: 1.39-4.50, p = 0.002], having relapsed TB infection [COR 0.46, 95% CI: 0.23-0.93, p = 0.031], receiving ART [COR 1.95, 95% CI: 1.28-2.97, p = 0.002] and Cotrimoxazole [COR 2.03, 95% CI: 1.12-3.66, p = 0.019] were factors significantly associated with successful treatment. After adjusting for confounders, successful treatment outcome were associated with being a female [AOR 1.6; 95% CI: 1.21-2.22, p = 0.001], diagnosis of TB in 2014 [AOR 1.90; 95% CI: 1.04-3.45, p = 0.036] and 2015 [AOR 2.43; 95% CI: 1.33-4.43, p = 0.004].. There is a high TB treatment success rate among HIV/TB co-infected patients in our setting, although below the target set by the WHO. Specific interventions aimed at enhancing patient outcomes are recommended.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Antitubercular Agents; Cameroon; Coinfection; Disease Management; Female; HIV; HIV Infections; Humans; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Risk Factors; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Objective : This study determined the prevalence of asymptomatic Plasmodium (P.) falciparum infection and anemia in adults living with HIV/AIDS (PLHIV) and compared malaria prevalence between 858 HIV-infected (PLHIV) and 272 uninfected individuals in Gabon where such information are lacking. Factors influencing malaria and anemia were also investigated.. Participants were screened for malaria. Available hemoglobin level, socio-demographic and use of prevention or treatment data were compared between both groups.. The prevalence of asymptomatic parasitemia was 13.5%, lower in PLHIV (7.1%) than uninfected individuals (33.8%) (p<0.01). Among the PLHIV, females (p<0.01), those aged below 25 years old (p=0.03), those with primary education (p=0.03) and those with a CD4 cell count below 200/mm3 (p=0.03) had a higher median parasitemia. Cotrimoxazole use was associated with a lower prevalence of malaria (p<0.01). Age below 25 years was independently associated with malaria in PLHIV (p<0.01). Anemia prevalence was 42.1% among the PLHIV, higher in the youngest and those with low CD4 cell count (p<0.01). P.falciparum-infected PLHIV aged below 25 years old, not under ART, with low CD4 cell count and under cotrimoxazole had the lowest median hemoglobin level.. The prevalence of asymptomatic malaria is low among the PLHIV while the burden of anemia is considerable. Age below 25 years and CD4 cell count are associated factors. The cotrimoxazole use reduces the frequency of malaria.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antimalarials; Asymptomatic Diseases; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; Gabon; HIV Infections; Humans; Malaria, Falciparum; Male; Middle Aged; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

This observational study recorded the malaria and sickle cell disease (SCD) profile of people living with HIV/AIDS (PLHA) and determined whether prophylactic co-trimoxazole (CTX) and the haemoglobin S (Hb S) allele influenced malaria episodes.. Sickling status, malaria episodes, and HIV type, as well as other data, were extracted retrospectively from the clinical records of 1001 patients attending the antiretroviral therapy clinic at Ridge Regional Hospital in Accra, Ghana between 2010 and 2015. Finger-prick capillary blood of returning patients (n=501) was tested for the haemoglobin (Hb) level and malaria, after information on malaria prevention methods was obtained through the administration of a questionnaire.. The use of insecticide-treated mosquito nets was low (22.8%). CTX prophylaxis showed no significant influence on the overall number of malaria episodes from 2010 to 2015; however, it did show a statistically significant relationship (p=0.026) with the time elapsed since the last malaria episode. Even though 19% of participants possessed Hb S, it had no influence on malaria episodes.. Hb S did not influence malaria in PLHA. Further studies in Hb SS and Hb SC are needed, as there are suggestions of increased frequency and severity of malaria. The impact of CTX prophylaxis on this cohort will be insightful.

Topics: Adult; AIDS-Related Opportunistic Infections; Anemia, Sickle Cell; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Female; Ghana; HIV Infections; Humans; Malaria; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This study assessed the incidence of tuberculosis (TB) and its predictors among adults living with HIV/AIDS in government health facilities in north-east Ethiopia.. A 5-year retrospective cohort study was conducted from May to June 2015 on 451 adult HIV/AIDS-infected individuals who enrolled in the HIV care clinics of government health facilities in north-east Ethiopia.. A total of 451 HIV-infected adults who newly enrolled in the adult HIV care clinic from 1 July 2010 with complete information were followed until May 2015.. The primary outcome was the proportion of patients diagnosed with TB or the TB incidence rate.. The incidence of TB was investigated in relation to years of follow-up.. The incidence of TB among adults living with HIV/AIDS in the first 3 years of follow-up was higher compared with that of subsequent years. Previous TB disease, no IPT, low BMI and haemoglobin level, advanced WHO clinical stage, and bedridden condition were the determinants of the incidence of TB. Therefore, addressing the significant predictors and improving TB/HIV collaborative activities should be strengthened in the study setting.

Topics: Adolescent; Adult; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Body Mass Index; Disease-Free Survival; Ethiopia; Female; HIV Infections; Humans; Incidence; Isoniazid; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Early mortality and morbidity remain high in children initiating antiretroviral therapy (ART), especially in sub-Saharan Africa. Many children still present with advanced human immunodeficiency virus (HIV) disease. Tuberculosis, pneumonia, and severe bacterial infections are the main causes of hospital admission in HIV-infected children. In contrast to adults with advanced HIV disease, cryptococcal disease is not common in childhood, although there is a peak in infancy and adolescence. Interventions such as TB screening in symptomatic children, and isoniazid and cotrimoxazole prophylaxis should be implemented. There is evidence suggesting that rapid initiation (within 1 week) of ART in children with severe malnutrition or those with advanced HIV disease admitted to hospital is not beneficial and should be delayed until their condition has been stabilized. Research informing the prevention of severe bacterial infections, the management of pediatric immune reconstitution inflammatory syndrome, and other potential strategies to decrease morbidity and mortality in HIV-infected children are urgently needed.

Topics: Adolescent; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bacterial Infections; Child; Child, Hospitalized; Child, Preschool; HIV Infections; Humans; Infant; Isoniazid; Malnutrition; Mass Screening; Morbidity; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Submicroscopic malaria infections contribute to malaria transmission. Describing the extent of the parasite reservoir is of importance. In people living with human immunodeficiency virus (HIV), the frequency of subpatent malaria infections is rarely reported. The aim of the present study was to determine the frequency of submicroscopic infections in people living with HIV in Gabon and its relationship with cotrimoxazole (CTX) use.. A survey was conducted in two health care centres in rural areas (Koulamoutou and Oyem) and three in urban areas (Libreville) of Gabon from March 2015 to June 2016. Blood samples were collected from consenting people living with HIV with a negative blood smear. Information on CTX and antiretroviral therapy intake was recorded from the medical file of the patient and through an interview. For molecular analysis, the Plasmodium small subunit ribosomal RNA gene was amplified by nested polymerase chain reaction.. Submicroscopic infections were detected in 10.1% (n=12/119) of the people living with HIV, more frequently in those residing in rural areas (15.1%) compared with urban areas (2.1%) (p<0.01). The proportion of anaemic patients was 1.74-fold more frequent in malaria-infected patients, although not statistically significant. Submicroscopic infections frequency did not vary according to CTX intake (p=0.6).. The present pilot study highlights a non-negligible frequency of submicroscopic malaria infections in people living with HIV from rural areas, but no relationship with CTX intake was found.

Topics: Adult; Antimalarials; Carrier State; Female; Gabon; HIV Infections; Humans; Malaria, Falciparum; Male; Middle Aged; Pilot Projects; Plasmodium falciparum; Polymerase Chain Reaction; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3-12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP-SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP-SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below half maximal inhibitory concentrations (IC50) for

Topics: Anti-Retroviral Agents; Antimalarials; Drug Resistance; Female; Folic Acid Antagonists; HIV; HIV Infections; HIV Seroprevalence; Humans; Incidence; Infant; Insecticide-Treated Bednets; Malaria, Falciparum; Male; Mutation; Plasmodium falciparum; Pre-Exposure Prophylaxis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

In sub-Saharan Africa, HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes. In Kenya, policy states women should be tested for all four conditions (malaria only if febrile) at first antenatal care (ANC) visit. In practice, while HIV screening is conducted, coverage of screening for the others is suboptimal and early pregnancy management of illnesses is compromised. This is particularly evident at rural dispensaries that lack laboratories and have parallel programmes for HIV, reproductive health and malaria, resulting in fractured and inadequate care for women.. A longitudinal eight-month implementation study integrating point-of-care diagnostic tests for the four conditions into routine ANC was conducted in seven purposively selected dispensaries in western Kenya. Testing proficiency of healthcare workers was observed at initial training and at three monthly intervals thereafter. Adoption of testing was compared using ANC register data 8.5 months before and eight months during the intervention. Fidelity to clinical management guidelines was determined by client exit interviews with success defined as ≥90% adherence.. For first ANC visits at baseline (n = 529), testing rates were unavailable for malaria, low for syphilis (4.3%) and anaemia (27.8%), and near universal for HIV (99%). During intervention, over 95% of first attendees (n = 586) completed four tests and of those tested positive, 70.6% received penicillin or erythromycin for syphilis, 65.5% and 48.3% received cotrimoxazole and antiretrovirals respectively for HIV, and 76.4% received artemether/lumefantrine, quinine or dihydroartemisinin-piperaquine correctly for malaria. Iron and folic supplements were given to nearly 90% of women but often at incorrect doses.. Integrating point-of-care testing into ANC at dispensaries with established HIV testing programmes resulted in a significant increase in testing rates, without disturbing HIV testing rates. While more cases were detected and treated, treatment fidelity still requires strengthening and an integrated monitoring and evaluation system needs to be established.

Topics: Adult; Anemia; Anti-Bacterial Agents; Anti-HIV Agents; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Dietary Supplements; Erythromycin; Female; Folic Acid; Guideline Adherence; Health Personnel; HIV Infections; Humans; Iron, Dietary; Kenya; Laboratory Proficiency Testing; Longitudinal Studies; Malaria; Penicillins; Point-of-Care Testing; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Complications, Infectious; Prenatal Care; Quinine; Quinolines; Syphilis; Trimethoprim, Sulfamethoxazole Drug Combination

Although Pneumocystis jiroveci pneumonia (PCP) is a frequent manifestation of acquired immune deficiency syndrome (AIDS), the granulomatous form is uncommon. Here, we present an unusual case of granulomatous PCP consequent to immune reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral therapy. A 36-year-old woman with human immunodeficiency virus (HIV) presented with cough and dyspnea that were attributed to typical PCP associated with AIDS. She was successfully treated with antibiotic, steroid, and antiretroviral therapies. After six months, however, she presented with consolidating lung lesions caused by bronchial obstruction from PCP granulomatous disease. Although antibiotics were ineffective, the effectiveness of steroid therapy suggested a diagnosis of granulomatous IRIS caused by persistent PCP antigens. Physicians should strongly suspect PCP in HIV-positive patients with nodular lung lesions and must remain aware that these lesions, if immune in origin, might not respond to antimicrobial therapy.

Topics: Adult; Anti-Infective Agents, Urinary; Antiretroviral Therapy, Highly Active; Bronchoscopy; Female; Granuloma, Respiratory Tract; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Optimal treatment success rates are critical to end tuberculosis in Namibia. Despite the scale-up of high quality directly observed therapy short-course strategy (DOTS) in Namibia, treatment success falls short of the global target of 90%. The objective of this study was to ascertain the predictors of treatment success rates under DOTS in Namibia to provide future direction.. A nation-wide comparative analysis of predictors of treatment success was undertaken. Tuberculosis cases in the electronic tuberculosis register were retrospectively reviewed over a 10-year period, 2004-2016. The patient, programmatic, clinical, and treatment predictors of treatment success were determined by multivariate logistic regression modeling using R software.. 104,603 TB cases were registered at 300 DOTS sites in 37 districts. The 10-year period treatment success rate was 80%, and varied by region (77.2%-89.2%). The patient's sex and age were not significant predictors. The independent predictors for treatment success as were: Region of DOTS implementation (p=0.001), type of directly observed treatment (DOT) supporter (p<0.001), sputum conversion at 2 months (p=0.013), DOT regimen (p<0.001), cotrimoxazole prophylaxis (p=0.002), and HIV co-infection (p=0.001).. Targeted programmatic, clinical and treatment interventions are required to enhance DOTS treatment success in Namibia. These are now ongoing.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antitubercular Agents; Coinfection; Directly Observed Therapy; Female; HIV Infections; Humans; Male; Namibia; Registries; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Globally, HIV and tuberculosis (TB) are a leading cause of death if they occur as co-morbidities in affected individuals. The aim of this study was to evaluate the collaboration between TB and HIV control activities by determining the co-morbidity rate in Oromia Region, Ethiopia, during the period 2009-2015.. A retrospective health facility-based study was conducted. Data were collected from health facilities implementing the directly observed treatment short-course (DOTS) strategy in the region. A structured World Health Organization (WHO) reporting format was used as the data collection tool. Pre-antiretroviral therapy (ART)/voluntary counselling and testing for HIV (VCT) and TB unit registers were considered as the data sources. Data were collected quarterly and analyzed using IBM SPSS Statistics version 20. The odds ratio was used to assess statistical differences among variables.. A total of 115268 TB patients were counselled and tested for HIV during the study period. Among the patients tested, 60086 (52.1%) were male, of whom 13680 (11.8%) were found to have an HIV infection. Among TB patients who were co-infected with HIV, there were slightly higher odds of HIV infection in females than in males (odds ratio 1.13, 95% confidence interval 1.09-1.17). Between 2009 and 2013, about 56% of TB and HIV co-morbid patients were put on co-trimoxazole preventive therapy (CPT) and 35% on ART. HIV infection occurred predominantly within the age group of 25-34 years (31%). On the other hand, 197152 HIV-infected patients were screened for TB symptoms and 8.4% were found to have active TB. The odds of having TB among males who were initially infected with HIV were higher as compared to females (odds ratio 1.31, 95% confidence interval 1.27-1.37).. The prevalence of TB and HIV co-morbidity was 11.8% at TB clinics in the region. Low proportions of co-infected patients were put on CPT and ART. Therefore, it is essential to strengthen the WHO recommended TB and HIV collaborative activities in the region to reduce the burden of co-morbidity and mortality.

Topics: Adolescent; Adult; Anti-Retroviral Agents; Child; Child, Preschool; Communicable Disease Control; Comorbidity; Ethiopia; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Male; Middle Aged; Outcome and Process Assessment, Health Care; Prevalence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; World Health Organization; Young Adult

 The World Health Organization aims to reduce tuberculosis (TB) mortality rate from 15% in 2015 to 6.5% by 2025..  This study determined the profile of TB and human immunodeficiency virus (HIV) co-infected patients who died in Mahalapye District, Botswana, while on anti-TB medication and the factors that contributed to such outcome..  The study was conducted in the Mahalapye Health District in Botswana..  This was a cross-sectional study that reviewed patient records from the Mahalapye District Health Management Team Electronic Tuberculosis Register from January 2013 to December 2015..  The majority of the TB and HIV co-infected patients were on antiretroviral therapy (ART) (486 [81.63%]) or were initiated cotrimoxazole preventive therapy (CPT) (518 [87.2%]) while taking anti-TB treatment. Seventy-three (13.6%) TB and HIV co-infected patients died before completing anti-TB treatment. Three-quarters (54 [74.4%]) of patients who died before completing anti-TB treatment were on ART, among them two patients who were on ART at least 3 months prior to commencing anti-TB. Also, the majority (64 [87.7%]) of TB and HIV co-infected patients were commenced on CPT prior to death. There was a bimodal density curve of death occurrence in those who did not commence ART and in those who did not commence CPT..  This study established that TB and HIV co-infected patients had a TB mortality of 13.6%. A high mortality rate was observed during the first 3 months in those who did not take ART and during the second and the fifth month in those who did not commence CPT. Further study is needed to clarify this matter.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Antitubercular Agents; Botswana; Coinfection; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Young Adult

Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria.. To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.. This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.. Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9).. The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; CD4 Lymphocyte Count; Coinfection; Cross-Sectional Studies; Female; HIV; HIV Infections; Humans; Malaria; Male; Middle Aged; Nigeria; Plasmodium; Plasmodium falciparum; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: HIV Infections; Humans; Infant; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV)-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear.. We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n = 1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity.. CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64 [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI, 1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09-2.06]), after adjusting for CPT.. CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

Topics: Adolescent; Adult; Antimalarials; Asymptomatic Infections; Female; HIV Infections; Humans; Infant; Malaria; Malawi; Male; Middle Aged; Morbidity; Parasitemia; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We describe two Malawian adults on successful antiretroviral therapy who experienced frequent malaria episodes after stopping cotrimoxazole prophylaxis. We argue that, in addition to stopping cotrimoxazole, diminished malaria immunity and drug interactions between efavirenz and artemether-lumefantrine may have played a causative role in the recurrent malaria our patients experienced.

Topics: Adult; Anti-HIV Agents; Antimalarials; Antiretroviral Therapy, Highly Active; Drug Interactions; Female; HIV Infections; Humans; Malaria; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm. Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm. Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region.

Topics: Adult; Africa, Western; Anti-HIV Agents; Antimalarials; CD4 Lymphocyte Count; Cohort Studies; Female; HIV Infections; HIV-1; Humans; Incidence; Malaria; Male; Multivariate Analysis; Proportional Hazards Models; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

To describe the cascade of care to HIV mother-to-child transmission (PMTCT) in a Rio de Janeiro reference paediatric clinic and evaluate the main factors possibly associated with HIV transmission.. Data on antenatal care (ANC), perinatal and neonatal assistance to HIV-infected and HIV-exposed but uninfected children assisted in the clinic from 1996 to 2013 were collected. The cascade of care was graphically demonstrated, and possible factors associated with HIV infection were described using regression models for bivariate and multivariate analysis. We imputed missing values of explanatory variables for the final model.. A total of 989 children were included in the analysis: 211 were HIV and 778 HEU. Graphically, the HIV PMTCT cascade of care improved from 1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main factor independently associated with the HIV infection over time was breastfeeding. In the period 1996/2000, the lack of antiretroviral use during labour was associated HIV transmission. While in 2001/2007, other modes of delivery but elective Caesarean section, and lack of maternal antiretroviral use during ANC were associated with HIV transmission. In the last period, the main factor associated with transmission was the lack of maternal ANC.. The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a problem, and better access to ANC is needed.

Topics: Adult; Anti-HIV Agents; Brazil; Breast Feeding; Contraindications; Female; HIV Infections; Humans; Infant; Infant Formula; Infant, Newborn; Infectious Disease Transmission, Vertical; Maternal Age; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult; Zidovudine

Given the potential of cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV-exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with antiretroviral agents that have overlapping toxicity profiles.. We used data from the Breastfeeding, Antiretrovirals, and Nutrition study (2004-2010) to evaluate the association of CPT and antiretrovirals with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models, according to time-varying CPT (implemented June 2006), antiretroviral treatment arm (maternal triple antiretroviral, infant nevirapine, or none during 6 months of breastfeeding), and their interaction. The effects of these treatments on hemoglobin, neutrophil, and alanine aminotransferase levels were assessed using linear mixed models.. In Cox models, CPT was associated with an increase in severe neutropenia [hazard ratio 1.97 (1.01, 3.86)] and a decrease in severe anemia (hazard ratio 0.65 (0.48, 0.88)]. Interactions between CPT and antiretroviral treatment were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of antiretroviral drug exposure.. In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent.

Topics: Adolescent; Adult; Alanine Transaminase; Anti-Bacterial Agents; Anti-Retroviral Agents; Antimalarials; Bacterial Infections; Chemoprevention; Drug Interactions; Female; Hemoglobins; HIV Infections; Humans; Infant; Infant, Newborn; Leukocyte Count; Malaria; Malawi; Male; Pregnancy; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed.. A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX.. Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy.. In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

Topics: Africa South of the Sahara; Antimalarials; Coinfection; Cost-Benefit Analysis; Drug Combinations; Female; HIV Infections; Humans; Malaria; Models, Theoretical; Pregnancy; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Emphasis on adolescent HIV has increased worldwide as antiretroviral treatment has greatly extended life expectancies of HIV-positive children. Few evidence-based guidelines exist on the optimal time to disclose to an adolescent living with HIV (ALHIV); little is known about the medical effects of disclosure. This study looked to determine whether disclosure is associated with improved medical outcomes in ALHIV. Prior work has tended to be qualitative, cross-sectional, and with an emphasis on psychosocial outcomes. This paper addresses the adolescent cohort retrospectively (longitudinally), building upon what is already known about disclosure.. Retrospective, longitudinal clinical record reviews of ALHIV seen at Kericho District Hospital between April 2004 and November 2012 were performed. Patient demographics and clinical outcomes were systematically extracted. The student's t-test was used to calculate changes in mean CD4 count, antiretroviral therapy (ART), and cotrimoxazole adherence pre- vs. post-disclosure. Linear regression modelling assessed for trends in those clinical outcomes associated with age of disclosure.. Ninety-six ALHIV (54 female, 42 male) were included; most (73%) entered care through the outpatient department. Nearly half were cared for by parents, and 20% experienced a change in their primary caregiver. The mean time in the study was 2.47 years; mean number of visits 10.97 per patient over the mean time in the study. Mean disclosure age was 12.34 years. An increase in mean ART adherence percentage was found with disclosure (0.802 vs. 0.917; p = 0.0015). Younger disclosure age was associated with significantly higher mean CD4 counts over the course of the study (p = 0.001), and a nonsignificant trend toward a higher mean ART adherence percentage (p = 0.055).. ART adherence and improved immunologic status are both associated with disclosure of HIV infection to adolescent patients. Disclosure of an HIV diagnosis to an adolescent is an important means to improve HIV care.

Topics: Adolescent; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Cross-Sectional Studies; Female; HIV; HIV Infections; Humans; Kenya; Male; Patient Compliance; Professional-Patient Relations; Retrospective Studies; Rural Population; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Truth Disclosure; Young Adult

Cystoisospora belli infection is one of the most important causes of watery diarrhea in patients with HIV and causes high rates of morbidity and mortality.. A retrospective study was conducted in patients with HIV and diarrhea by C. belli. Clinical and laboratory characteristics were collected by analyzing clinical records.. Four had recurrent diarrhea despite receiving secondary prophylaxis with cotrimoxazole and specific treatment, two of which had a good viral and immunological response to highly active antiretroviral therapy (HAART) at the time of diagnosis and antiparasitic treatment. While the remaining three did not receive prophylaxis, neither did HAART (two of them), but they responded well to treatment.. C. belli is an important cause of diarrhea in HIV patients on HAART and prophylaxis, being able to have different clinical evolution. We suggest that persistent infection may be due to drug failure by intrinsic or extrinsic to the parasite causes, or to defects in restoration of the intestinal immune system, or both.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Coccidiosis; Diarrhea; Female; HIV Infections; Humans; Male; Middle Aged; Peru; Retrospective Studies; Sarcocystidae; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Initiation of antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) is recommended for tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected patients to prevent opportunistic infection. The aim of this study was to assess the prevalence of HIV among TB patients and initiation of ART and provision of CPT for TB/HIV co-infected patients in Hawassa university referral hospital.. A five year document review was done on 1961 TB patients who are registered at TB clinic of Hawassa university referral hospital from September 2009 to august 2014. Data were collected using checklist. Data analysis was done by using SPSS version 20 software. Bivariate and multivariate logistic regression analysis was used to determine the predictors of TB/HIV co-infection.. Among 1961 TB patients diagnosed in the hospital, 95% (1765) were screened for HIV. Of these, 13.9% (246) were HIV positive. Out of 246 TB/HIV co-infected patients 31.7% (78/246) and 37.4% (92/246) were enrolled to start ART and CPT respectively. Roughly the trends of TB/HIV co-infection decreased with increased linkage to CPT, while linkage to ART was not regular across the year. The rate of TB/HIV co-infection was significantly associated with type of TB.. Although, trend of HIV among TB patients has decreased across the year, only a minority of co-infected patients was linked to start ART and CPT. Therefore, screening of all TB patients for HIV and linkage of co-infected patients to HIV care to start ART and CPT should be strengthened in-line with the national guidelines.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Child; Child, Preschool; Coinfection; Ethiopia; Female; HIV Infections; Hospitals, University; Humans; Infant; Infant, Newborn; Logistic Models; Male; Mass Screening; Middle Aged; Prevalence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

HIV-associated TB is a serious public health problem in Myanmar. Study objectives were to describe national scale-up of collaborative activities to reduce the double burden of TB and HIV from 2005 to 2016 and to describe TB treatment outcomes of individuals registered with HIV-associated TB in 2015 in the Mandalay Region.. Secondary analysis of national aggregate data and, for treatment outcomes, a cohort study of patients with HIV-associated TB in the Mandalay Region.. The number of townships implementing collaborative activities increased from 7 to 330 by 2016. The number of registered TB patients increased from 1577 to 139 625 in 2016, with the number of individuals tested for HIV increasing from 432 to 114 180 (82%) in 2016: 10 971 (10%) were diagnosed as HIV positive. Uptake of co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) nationally in 2016 was 77% and 52%, respectively. In the Mandalay Region, treatment success was 77% and mortality was 18% in 815 HIV-associated TB patients. Risk factors for unfavourable outcomes and death were older age (≥45 years) and not taking CPT and/or ART.. Myanmar is making good progress with reducing the HIV burden in TB patients, but better implementation is needed to reach 100% HIV testing and 100% CPT and ART uptake in TB-HIV co-infected patients.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antitubercular Agents; Cohort Studies; Cooperative Behavior; Delivery of Health Care; Female; HIV Infections; Humans; Male; Middle Aged; Myanmar; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

The antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), is generally used for prophylaxis in HIV individuals to protect them from Pneumocystis jiroveci infection. Long-term use of TMP-SMX develops drug resistance among bacteria in HIV patients. The study was aimed to detect the TMP-SMX resistance genes among gram-negative bacteria from HIV patients. TMP-SMX-resistant isolates were detected by the Kirby-Bauer disc diffusion method. While TMP resistance genes such as dfrA1, dfrA5, dfrA7, and dfrA17 and SMX resistance genes such as sul1 and sul2 were detected by multiplex PCR, class 1 and class 2 integrons were detected by standard monoplex PCR. Of the 151 TMP-SMX-resistant bacterial isolates, 3 were positive for sul1 alone, 48 for sul2 alone, 11 for dfrA7 alone, 21 for sul1 and sul2, 1 for sul1 and dfrA7, 23 for sul2 and dfrA7, 2 for sul2 and dfrA5, 41 for sul1, sul2, and dfrA7, and 1 for sul2, dfrA5, and dfrA7. Of 60 TMP-SMX-resistant isolates positive for integrons, 44 had class 1 and 16 had class 2 integrons. It was found that the prevalence of sul genes (n = 202; p < 0.001) was higher compared with dfr genes (n = 80; p < 0.001), and 87.4% (n = 132; p < 0.001) of TMP-SMX-resistant isolates also were positive for β-lactamase production. This type of study is reported for the first time from HIV patients in India. Therefore, this study indicates that dissemination of TMP-SMX resistance genes and class 1 and class 2 integrons along with β-lactamase production among gram-negative bacteria in HIV patients will certainly make their treatment to bacterial infections more complicated in clinical settings.

Topics: Anti-Bacterial Agents; beta-Lactamases; Coinfection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression Regulation, Bacterial; Genes, Bacterial; HIV Infections; Humans; India; Integrons; Pneumocystis carinii; Pneumonia, Pneumocystis; Primary Prevention; Trimethoprim, Sulfamethoxazole Drug Combination

People living with human immunodeficiency virus (HIV) who have not yet initiated antiretroviral therapy (ART) can benefit from being engaged in care and utilizing preventive interventions. Community-based peer support may be an effective approach to promote these important HIV services.. After conducting a randomized trial of the impact of peer support on pre-ART outcomes, we conducted a qualitative evaluation to better understand trial implementation, processes, and results. Overall, 75 participants, including trial participants (clients), peer supporters, and clinic staff, participated in 41 in-depth interviews and 6 focus group discussions. A situated Information Motivation, and Behavioral skills model of behavior change was used to develop semi-structured interview and focus group guides. Transcripts were coded and thematically synthesized.. We found that participant narratives were generally consistent with the theoretical model, indicating that peer support improved information, motivation, and behavioral skills, leading to increased engagement in pre-ART care. Clients described how peer supporters reinforced health messages and helped them better understand complicated health information. Peer supporters also helped clients navigate the health system, develop support networks, and identify strategies for remembering medication and clinic appointments. Some peer supporters adopted roles beyond visiting patients, serving as a bridge between the client and his or her family, community, and health system. Qualitative results demonstrated plausible processes by which peer support improved client engagement in care, cotrimoxazole use, and safe water vessel use. Challenges identified included insufficient messaging surrounding ART initiation, lack of care continuity after ART initiation, rare breaches in confidentiality, and structural challenges.. The evaluation found largely positive perceptions of the peer intervention across stakeholders and provided valuable information to inform uptake and scalability of the intervention. Study findings also suggest several areas for improvement for future implementation of pre-ART peer support programs.. NCT01366690 . Registered June 2, 2011.

Topics: Anti-HIV Agents; Antimalarials; Counseling; Drinking Water; Female; Focus Groups; HIV Infections; Humans; Insecticide-Treated Bednets; Male; Models, Theoretical; Motivation; Outcome and Process Assessment, Health Care; Patient Navigation; Patient Participation; Peer Group; Preventive Medicine; Randomized Controlled Trials as Topic; Residence Characteristics; Social Support; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8

Topics: Animals; Antimalarials; CD8-Positive T-Lymphocytes; HIV Infections; Immunization; Interferon-gamma; Life Cycle Stages; Malaria; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Opportunistic Infections; Plasmodium; Sporozoites; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculosis (TB) is a major cause of morbidity and mortality in human immunodeficiency virus (HIV) infected patients. However, anti-tuberculosis drugs can cause cutaneous adverse drug reactions (CADRs). This study was conducted to evaluate differences in CADR incidence between low and high CD4 cell count in patients with low and high CD4 cell count and to identify other risk factors for CADR in HIV-TB co-infected patients.. In a retrospective cohort of adult HIV-TB co-infected patients receiving standard anti-tuberculosis treatment between January 2008 and December 2015 at Vajira Hospital, Bangkok, Thailand, baseline demographic, clinical characteristics and factors associated with CADRs, including CD4 cell count status, were collected.. Of 307 patients enrolled, CADRs occurred in 48 during the 6-month period of anti-tuberculosis treatment (incidence rate 0.41 events/person-year). Maculopapular rash was the most prevalent CADR. Low CD4 cell count was not associated with CADRs. Cox regression analysis revealed that moderate decrease in the glomerular filtration rate, history of drug hypersensitivity and concomitant cotrimoxazole use were all associated with CADRs. Concomitant antiretroviral therapy use was associated with lower risk of CADRs. No difference in the time to CADRs between patients with lower and higher CD4 cell count could be demonstrated.. CADRs are common in HIV-TB co-infected patients. Early recognition and prompt withdrawal of the offending agent can prevent complications and improve TB care.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; CD4 Lymphocyte Count; Cohort Studies; Drug Eruptions; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Topics: Aged; Aging; Anti-Infective Agents; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Carcinoma, Non-Small-Cell Lung; Cisplatin; Emtricitabine; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Lung Neoplasms; Middle Aged; Oxazines; Pemetrexed; Piperazines; Pneumocystis carinii; Pneumonia, Pneumocystis; Pyridones; Tenofovir; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.. Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.. Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.. Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.

Topics: Adolescent; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Asia; CD4 Lymphocyte Count; Child; Female; Growth; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Reverse Transcriptase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult

Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.. Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.. Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.. Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Asia; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Infant; Male; Malnutrition; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Raquel Gonzalez and colleagues highlight an urgent need to evaluate antimalarials that can be safely administered to HIV-infected pregnant women on antiretroviral treatment and cotrimoxazole prophylaxis.

Topics: Africa; Anti-HIV Agents; Antimalarials; Female; HIV Infections; Humans; Malaria; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

Skin and soft tissue infection (SSTIs) due to Staphylococcus aureus, particularly community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), are common in human immunodeficiency virus (HIV)-infected populations in the United States. Studies have differed as to the importance of epidemiological and immunological factors in this relationship, and have employed conflicting strategies for variable selection in multivariate analyses. Developments in causal inference methods in epidemiology have emerged in the last decade to clarify relationships between variables and identify appropriate variables to include in and exclude from multivariate analysis. In this paper, we develop a causal diagram to clarify the pathways linking CA-MRSA and HIV. We focus on the role played by trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, prescribed to many severely immunocompromised HIV patients and potentially protective against SSTIs, which both mediates and moderates the relationship between immunological parameters and SSTI risk. We demonstrate, using simulated data, that statistical models may yield biased results if they do not account for how HIV viral load may also be a marker of adherence to TMP-SMX prophylaxis. We conclude with a proposed causal model that includes both the epidemiological as well as immunological factors that may explain the increased risk of initial and recurrent SSTI risk in HIV-infected populations.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Community-Acquired Infections; HIV Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Models, Theoretical; Risk Factors; Skin Diseases, Infectious; Soft Tissue Infections; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood.. Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.. There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.. The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.

Topics: Antimalarials; CD4-Positive T-Lymphocytes; Chemoprevention; Cytokines; Female; HIV Infections; Humans; Immunophenotyping; Infant; Malaria, Falciparum; Malawi; Male; Maternal Exposure; Plasmodium falciparum; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Disease Progression; Drug Therapy, Combination; Emigrants and Immigrants; Germany; HIV Infections; Humans; Male; Medication Adherence; Middle Aged; Nigeria; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

The relevance of vaginal colonization of pregnant women by Escherichia coli is poorly understood, despite these strains sharing a similar virulence profile with other extraintestinal pathogenic E. coli producing severe obstetric and neonatal infections. We characterized the epidemiology, antimicrobial susceptibility and virulence profiles of 84 vaginal E. coli isolates from pregnant women from Rabat (Morocco) and Manhiça (Mozambique), two very distinct epidemiological settings. Low levels of antimicrobial resistance were observed to all drugs tested, except for trimethoprim-sulfamethoxazole in Manhiça, where this drug is extensively used as prophylaxis for opportunistic HIV infections. The most prevalent virulence factors were related to iron acquisition systems. Phylogroup A was the most common in Rabat, while phylogroups E and non-typeable were the most frequent in Manhiça. Regardless of the apparently "low virulence" of these isolates, the frequency of infections is higher and the outcomes more devastating in constrained-resources conditions, especially among pregnant women and newborns.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; HIV Infections; Humans; Microbial Sensitivity Tests; Morocco; Mozambique; Phylogeny; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Vagina; Virulence; Virulence Factors

The purpose of this study is to propose the Least Absolute Shrinkage and Selection Operators procedure (LASSO) as an alternative to conventional variable selection models, as it allows for easy interpretation and handles multicollinearities. We developed a model on the basis of LASSO-selected parameters in order to link associated demographical, socio-economical, clinical and immunological factors to performing tuberculosis screening in HIV-positive patients in Ghana.. Applying the LASSO method and multivariate logistic regression analysis on a large public health data set, we selected relevant predictors related to tuberculosis screening.. One Thousand Ninety Five patients infected with HIV were enrolled into this study with 691 (63.2 %) of them having tuberculosis screening documented in their patient folders. Predictors found to be significantly associated with performance of tuberculosis screening can be classified into factors related to the clinician's perception of the clinical state, as well as those related to PLHIV's awareness. These factors include newly diagnosed HIV infections (n = 354 (32.42 %), aOR 1.84), current CD4+ T cell count (aOR 0.92), non-availability of HIV type (n = 787 (72.07 %), aOR 0.56), chronic cough (n = 32 (2.93 %), aOR 5.07), intake of co-trimoxazole (n = 271 (24.82 %), aOR 2.31), vitamin supplementation (n = 220 (20.15 %), aOR 2.64) as well as the use of mosquito bed nets (n = 613 (56.14 %), aOR 1.53).. Accelerated TB screening among newly diagnosed HIV-patients indicates that application of the WHO screening form for intensifying tuberculosis case finding among HIV-positive individuals in resource-limited settings is increasingly adopted. However, screening for TB in PLHIV is still impacted by clinician's perception of patient's health state and PLHIV's health awareness. Education of staff, counselling of PLHIV and sufficient financing are needed for further improvement in implementation of TB screening for all PLHIV. The LASSO approach proved a convenient method for automatic variable selection in a large public health data set that requires efficient and fast algorithms.. ClinicalTrials.gov NCT01897909 (July 5, 2013).

Topics: Adult; Algorithms; CD4-Positive T-Lymphocytes; Female; Ghana; HIV Infections; Humans; Logistic Models; Male; Mass Screening; Middle Aged; Multivariate Analysis; Population Surveillance; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized.. Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2.. A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%.. Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Antibiotic Prophylaxis; Asia; Body Height; Body Weight; Child; Child Development; Child, Preschool; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men.

Topics: Adult; Aged; Anti-Infective Agents; Ceftriaxone; Drug Therapy, Combination; Female; Fluoroquinolones; HIV Infections; Hospitals; Humans; Logistic Models; Male; Middle Aged; Multilocus Sequence Typing; Multivariate Analysis; Retrospective Studies; Salmonella enterica; Salmonella Infections; Serogroup; Sex Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever; Vietnam

Sulfonamide hypersensitivity has a high incidence in HIV infection and correlates with low CD4+ counts, but the mechanisms are not understood. The aims of this study were to determine whether trimethoprim/sulfamethoxazole (TMP/SMX) led to SMX adduct formation, immunogenicity, or signs of drug hypersensitivity in SIV-infected rhesus macaques, and whether differences in antioxidants, pro-inflammatory mediators, or SMX disposition were predictive of drug immunogenicity.. Four of 9 of SIV-positive (44%), and 3 of 7 SIV negative (43%) macaques had drug-responsive T cells or antibodies to SMX. Two macaques developed facial or truncal rash; these animals had the highest levels of lymph node drug adducts. Antioxidants, pro-inflammatory mediators, and SMX metabolites were not predictive of drug immunogenicity; however, the Mamu DRB1*0401/0406/0411 genotype was significantly over-represented in immune responders.. Unlike other animal models, macaques develop an immune response, and possible rash, in response to therapeutic dosages of TMP/SMX. Studying more animals with CD4+ counts <200cells/μl, along with moderately restricted ascorbate intake to match deficiencies seen in humans, may better model the risk of SMX hypersensitivity in HIV-infection. In addition, the role of Mamu-DRB1 genotype in modeling drug hypersensitivity in retroviral infection deserves further study.

Topics: Animals; Anti-Infective Agents; Antioxidants; Ascorbic Acid; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytochrome-B(5) Reductase; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Glutathione; HIV Infections; Interferon-gamma; Lipopolysaccharides; Lymph Nodes; Macaca mulatta; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Coinfection with malaria and HIV is common in Sub-Saharan Africa. In the advent of a decline in the global incidence of malaria, it is important to generate updated data on the burden of malaria in people living with HIV (PLWHIV). This study was designed to determine the prevalence of malaria in PLWHIV in Yaounde, Cameroon, as well determine the association between CD4 (+) T cell count and malaria in the study population.. In a cross sectional study performed between April 2015 and June 2016, 355 PLWHIV were enrolled and blood samples were collected for analysis. Complete blood count was performed using an automated haematology analyser (Mindray®, BC-2800) and CD4 (+) T cell count was performed using a flow cytometer (BD FASCount™). Giemsa-stained blood films were examined to detect malaria parasite. The Pearson's chi-square, student's T-test, ANOVA, and correlation analysis were all performed as part of the statistical analyses.. The prevalence of malaria observed in the study was 7.3 % (95 % CI: 4.8-10.6). No significant association was observed between the prevalence of malaria and age or gender. The prevalence of malaria was higher in participants who were not sleeping in insecticide treated bed nets, ITNs (p < 0.001); and in participants who were not on cotrimoxazole prophylaxis (p = 0.002). The prevalence of malaria (p < 0.001) and malaria parasite density (p = 0.005) were observed to be progressively higher in participants with CD4 (+) T cell count below 200cells/μl. Furthermore, the mean CD4 (+) T cell count was observed to be lower in participants coinfected with malaria compared to non-coinfected participants (323.5 vs 517.7) (p < 0.001). In this study, a negative correlation was observed between malaria parasite density and CD4 (+) T cell count (p = 0.019).. A low prevalence of malaria was observed in the study population. Some of the factors accounting for the low prevalence of malaria in this study population may include the health seeking habit of PLWHIV, the use of cotrimoxazole based chemoprophylaxis, and their cautious use of ITNs.

Topics: Adult; Antimalarials; Cameroon; Coinfection; Cross-Sectional Studies; Female; HIV Infections; Humans; Incidence; Insecticide-Treated Bednets; Malaria; Male; Middle Aged; Pre-Exposure Prophylaxis; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival.. The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight.. Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART.. This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Lost to Follow-Up; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Survival; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zambia

Although isoniazid preventive therapy (IPT) is effective in the prevention of tuberculosis (TB) in people living with the human immunodeficiency virus (PLHIV), patient adherence to this strategy is suboptimal.. This prospective cohort study was conducted in the HIV/AIDS (acquired immune-deficiency syndrome) out-patient chronic care unit of Dilla University Hospital, Dilla, Ethiopia, from May 2014 to February 2015. Adherence was defined as completion of the 6-month course of treatment with 90% of pills taken, as measured by diary and pill count. Data were collected on potential predictors, including patients' demographic and clinical characteristics. Univariable and multivariable logistic regression models were fitted to identify independent predictors of adherence to IPT.. Of 162 PLHIV included, 104 (64.2%) were adherent to IPT. In the final multivariable model, concomitant use of antiretroviral therapy (ART) and/or cotrimoxazole preventive therapy (CPT) was associated with adherence to IPT (OR 2.66, 95%CI 1.15-6.17). Experiencing a high level of HIV stigma and episodes of opportunistic infections tended to be associated with non-adherence to IPT (OR 0.51, 95%CI 0.25-1.04 and OR 0.14, 95%CI 0.02-1.15) in comparison to low stigma and no opportunistic infections, respectively.. PLHIV receiving ART or CPT were more likely to adhere to IPT.

Topics: Adult; Anti-Retroviral Agents; Antitubercular Agents; Ethiopia; Female; Follow-Up Studies; HIV Infections; Humans; Isoniazid; Male; Medication Adherence; Middle Aged; Outpatients; Pre-Exposure Prophylaxis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

TB and HIV are the most prevalent communicable diseases of major public health importance in the populations of sub-Saharan African countries, and an estimated 30 % of HIV infected persons have dual infection with TB. TB is the leading cause of death in HIV infected individuals, and HIV co-infected TB patients have multiple individual, disease specific and treatment related factors that can adversely affect their treatment outcomes. There is lack of evidence on the individual patient outcomes of HIV co-infected TB patients who receive anti-TB treatment. It is relevant to understand the differential patient outcomes of HIV co-infected TB patients and identify the factors that are associated with these outcomes.. A comparative analysis was done on the data from a random sample of 575 TB patients who were enrolled for TB treatment from January 2013 to December 2013 at eight health facilities in Ethiopia. A descriptive analysis was done on the data, and chi-square test and logistic regression analysis was conducted to compare TB treatment outcomes based on HIV status and to identify factors associated with these outcomes.. Out of a total of 575 TB patients enrolled into the study, 360 (62.6 %) were non-HIV infected, 169 (29.4 %) were HIV co-infected, and 46 (8 %) had no documented HIV status. The overall treatment success rate was 91.5 % for all the study participants. HIV co-infected TB patients have a treatment success rate of 88.2 % compared with 93.6 % for non-HIV infected study participants (P = 0.03). HIV co-infected TB patients had a significantly higher rate (11.8 % versus 6.4 %, P = 0.03) of unfavourable outcomes. The cure rate was significantly lower (10.1 % versus 24.2 %, P = 0.001) and the death rate higher in HIV co-infected TB patients (8.3 % versus 2.5 %, P = 0.014). Age and TB classification were significantly associated with treatment outcome. No association was found with starting ART, Cotrimoxazole prophylactic treatment or enrolment in HIV care.. There is high TB treatment success rate among patients who have been treated for TB, but the treatment success rate and the cure rate in HIV co-infected TB patients is lower than that observed in non-HIV infected patients. Patients with advanced age and those with smear positive pulmonary TB have unfavourable treatment outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Coinfection; Cross-Sectional Studies; Ethiopia; Female; HIV Infections; Humans; Male; Middle Aged; Prevalence; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) among human immunodeficiency virus (HIV)-infected patients, but the risk factors are not well defined. We sought to elucidate the risk factors for SSTI occurrence in an HIV cohort. This investigation was a retrospective, single-center cohort study, carried out during the period 2005-2009. In this cohort of 511 HIV-infected individuals, 133 SSTIs occurred in 87 individuals over 1,228.6 person-years of follow-up, for an incidence of 108 SSTIs/1,000 person-years [95 % confidence interval (CI) 87-135]. The incidence declined significantly over time (p < 0.01). In a multivariable Cox regression, diabetes [hazard ratio (HR) 2.01; 95 % CI 1.04-3.89], psoriasis (HR 5.77; 95 % CI 1.86-17.9), lymphedema (HR 6.84; 95 % CI 2.59-18.1), intravenous catheter presence (HR 3.38; 95 % CI 1.00-11.5), and HIV viral load greater than 1,000 copies/mL (HR 2.13; 95 % CI 1.33-3.41) were most strongly associated with development of the first SSTI. Trends toward an association between SSTI risk and Medicaid insurance (HR 1.67; 95 % CI 0.98-2.83) and sexually transmitted disease during follow-up (HR 1.66; 0.99-2.78) were present. CD4+ count and trimethoprim-sulfamethoxazole use were not associated with SSTI risk. HIV-infected individuals are at high risk for SSTIs. In a primarily urban, African-American cohort, we found that a number of immunologic and demographic factors were associated with SSTI risk.

Topics: Adult; Anti-Infective Agents; CD4 Lymphocyte Count; Cohort Studies; Community-Acquired Infections; Female; HIV Infections; Humans; Longitudinal Studies; Male; Methicillin; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Outpatients; Retrospective Studies; Risk Factors; Skin; Soft Tissue Infections; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Globally, diarrhea is the second leading cause of death in children less than 5 years of age. HIV-infected and HIV-exposed uninfected (HEU) children are at high risk of dying from diarrhea and may be more susceptible to the highest risk enteric pathogens. This increased risk associated with HIV infection and HIV exposure is likely multifactorial. Factors such as immunosuppression, proximity to individuals more likely to be shedding pathogens, and exposure to antimicrobial prophylaxis may alter the risk profile in these children. Current international guidelines do not differentiate management strategies on the basis of whether children are infected or affected by HIV, despite likely differences in etiologies and consequences. Reducing diarrhea mortality in high HIV prevalence settings will require strengthening of HIV testing and treatment programs; improvements in water, sanitation and hygiene interventions targeted at HIV-affected households; and reconsideration of the use of empiric antimicrobial treatment of pathogens known to infect HIV-infected and HEU children disproportionately.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child, Preschool; Diarrhea, Infantile; HIV Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

We report a unique case of acute bacterial prostatitis probably caused by Listeria monocytogenes in an HIV-infected patient. For the best of our knowledge, this is the first case reported of a patient with this association. Our case illustrates the protean clinical presentations that L. monocytogenes infections may adopt, particularly in immunocompromised patients.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; HIV Infections; Humans; Listeria monocytogenes; Listeriosis; Male; Prostatitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; CD4 Lymphocyte Count; Chickenpox; Child, Preschool; Clindamycin; Drug Therapy, Combination; Exanthema; Floxacillin; Herpesvirus 3, Human; HIV Infections; HIV-1; Humans; Male; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Child, Preschool; Chlorpheniramine; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV; HIV Infections; Humans; Nigeria; Prednisolone; Pruritus; Skin Tests; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection.. Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age.. Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period.. Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibody Formation; Female; HIV Infections; Humans; Immunity, Active; Immunoglobulin G; Infant; Malaria, Falciparum; Malawi; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole use is the standard of care for preventing Pneumocystis jirovecii pneumonia in sub-Saharan Africa but implementation remains slow. Co-trimoxazole is self- administered with uncertain adherence. Knowledge of co-trimoxazole use among HIV infected persons is unknown.. To assess knowledge, attitudes and practices of co-trimoxazole use among HIV infected adults evaluated for recurrent PTB in Kampala, Uganda.. A qualitative study utilizing 5 focus group discussions among 30 HIV infected PTB suspects at the national referral tuberculosis treatment centre in Kampala.. Males and females had similar median ages. 80% were currently on co-trimoxazole and 50% of participants were on HAART. Majority of participants defined co-trimoxazole as an analgesic. Few noted co-trimoxazole was a drug to treat cough and chest pain. However, few responses revealed that co-trimoxazole prevents opportunistic diseases among PLHIV. Most of participants believed HAART and anti-TB drugs work as co-trimoxazole thus it should not be taken together with them. This belief may lead to increased risk of opportunistic infections, morbidity and mortality.. We revealed gaps in understanding of co-trimoxazole use among study participants. We therefore recommend that more facts about co-trimoxazle as prophylaxis against P. jirovecii, bacterial and diarrheal pathogens should be incorporated in VCT fact sheets.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Ambulatory Care Facilities; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Cross-Sectional Studies; Female; Health Knowledge, Attitudes, Practice; HIV Infections; Hospitals, Teaching; Humans; Male; Qualitative Research; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Uganda

To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV).. We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200 cells/µL were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses.. The analysis involved 23 816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6 months of ART was 5.3 and 7.0 per 100 person-years, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.56-0.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6 months (HR: 0.65; 95% CI: 0.59-0.73), 12 months (HR: 0.58; 95% CI: 0.49-0.70), 18 months (HR: 0.49; 95% CI: 0.38-0.63) and 24 months (HR: 0.66; 95% CI: 0.48-0.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50 cells/µL (HR: 0.60; 95% CI: 0.54-0.67), 50-99 cells/µL (HR: 0.66; 95% CI: 0.56-0.78) and 100-199 cells/µL (HR: 0.78; 95% CI: 0.62-0.98).. Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries.. Évaluer si la prophylaxie par le cotrimoxazole administrée précocement au cours de la thérapie antirétrovirale (TAR) réduit la mortalité chez les adultes infectés par le virus de l'immunodéficience humaine (VIH) en Chine.. Nous avons effectué une étude de cohorte par observation rétrospective en utilisant les données de la base de données antirétrovirale gratuite nationale chinoise. Les patients âgés de plus de 14 ans qui ont commencé une TAR entre le 1er janvier 2010 et le 31 décembre 2012 et qui avaient un nombre de lymphocytes T CD4+ (cellules CD4+) à la ligne de base inférieur à 200 cellules/µL, ont été suivis jusqu'à leur décès, jusqu'à ce qu'ils soient perdus de vue au suivi ou jusqu'au 31 décembre 2013. Les rapports des risques (RR) pour plusieurs variables sont calculés en utilisant des analyses multivariées.. Le suivi. La mortalité chez les patients qui ont et qui n'ont pas commencé à prendre le cotrimoxazole au cours des 6 premiers mois de la TAR était de 5,3 et 7,0 pour 100 personnes-années, respectivement. Le cotrimoxazole était associé avec 37% de réduction de la mortalité (rapport des risques, RR: 0,63; intervalle de confiance à 95%, IC 95%: 0,56-0,70). Le cotrimoxazole ajouté à la TAR a réduit significativement la mortalité au cours du suivi des 6 derniers mois (RR: 0,65; IC 95%: 0,59–0,73), des 12 derniers mois (RR: 0,58; IC 95%: 0,49-0,70), des 18 derniers mois (RR: 0,49; IC 95%: 0,38-0,63) et des 24 derniers mois (RR: 0,66; IC 95%: 0,48-0,90). La réduction de la mortalité était évidente chez les patients avec un nombre de cellules CD4+ à la ligne de base inférieur à 50 cellules/µL (RR: 0,60; IC 95%: 0,54–0,67), 50–99 cellules/µL (RR: 0,66; IC 95%: 0,56-0,78) et 100-199 cellules/µL (RR: 0,78; IC 95%: 0,62-0,98).. La prophylaxie par le cotrimoxazole commencée précocement au cours de la TAR a réduit la mortalité et devrait être proposée aux patients infectés par le VIH dans les pays à revenu faible et à revenu intermédiaire.. Evaluar si la profilaxis con cotrimoxazol en una etapa temprana de la terapia antirretroviral (TAR) reduce la mortalidad en adultos de origen chino infectados por el virus de la inmunodeficiencia humana (VIH).. Se llevó a cabo un estudio de cohorte observacional retrospectivo utilizando los datos de la base de datos nacional de China de antirretrovirales de uso gratuito. Por otro lado, se realizó un seguimiento a pacientes mayores de 14 años que iniciaron el tratamiento con TAR entre el 1 de enero de 2010 y el 31 de diciembre de 2012 y con recuento basal de linfocitos T CD4+ (célula CD4+) inferior a 200 células/µl hasta su muerte, la pérdida de seguimiento o el 31 de diciembre de 2013. Se calcularon los cocientes de riesgos (CR) para diversas variables mediante análisis multivariados.. En el análisis participaron 23 816 pacientes infectados por el VIH, 2706 de los cuales fallecieron durante el seguimiento. La mortalidad entre los pacientes que iniciaron y no iniciaron el tratamiento con cotrimoxazol durante los primeros 6 meses de la TAR fue de 5,3 y 7,0 por 100 personas/años, respectivamente. Cotrimoxazol se asoció a una reducción del 37 % en la mortalidad (cociente de riesgos, CR: 0,63, intervalo de confianza del 95 %, IC: 0,56 – 0,70). Además de la TAR, cotrimoxazol redujo la mortalidad considerablemente durante el seguimiento de 6 meses (CR: 0,65; IC del 95 %: 0,59 – 0,73), 12 meses (CR: 0,58; IC del 95 %: 0,49 – 0,70), 18 meses (CR: 0,49; IC del 95 %: 0,38 – 0,63) y 24 meses (CR: 0,66; IC del 95 %: 0,48 – 0,90). La reducción de la mortalidad resultó evidente en pacientes con recuento basal de células CD4+ inferior a 50 células/µl (CR: 0,60; IC del 95 %: 0,54 – 0,67), 50 – 99 células/µl (CR: 0,66; IC del 95 %: 0,56 – 0,78) y 100 – 199 células/µl (CR: 0,78; IC del 95 %: 0,62 – 0,98).. La profilaxis con cotrimoxazol iniciada en una etapa temprana de la TAR redujo la mortalidad y debe ofrecerse a los pacientes infectados por el VIH en países de ingresos bajos y medios.. تقييم ما إذا كانت الوقاية باستخدام الكوتريموكسازول في مرحلة مبكرة خلال العلاج بمضادات الفيروسات القهقرية يقلل معدل الوفيات بين البالغين المصابين بفيروس العوز المناعي البشري في الصين.. أجرينا دراسة أترابية استرجاعية قائمة على الملاحظة باستخدام البيانات المستمدة من قاعدة بيانات مضادات الفيروسات القهقرية المجانية الوطنية في الصين. وتم متابعة المرضى الأكبر من 14 عاماً الذين استهلوا العلاج بمضادات الفيروسات القهقرية في الفترة من 1 كانون الثاني/ يناير 2010 حتى 31 كانون الأول/ ديسمبر 2012 وكان إحصاء الخلايا اللمفاوية التائية المساعدة (CD4+) عند خط الأساس لديهم أقل من 200 خلية/ميكرو لتر حتى الوفاة، أو فقدان المتابعة، أو حتى 31 كانون الأول/ ديسمبر 2013. وتم حساب نسب المخاطر لعدة متغيرات باستخدام التحليلات متعددة المتغيرات.. اشتمل التحليل على 23816 مريضاً مصاباً بفيروس العوز المناعي البشري، توفي منهم 2706 مريضاً أثناء المتابعة. وكان معدل الوفيات بين المرضى الذين استهلوا ولم يستهلوا استخدام الكوتريموكسازول خلال الستة أشهر الأولى من العلاج بمضادات الفيروسات القهقرية 5.3 و7.0 لكل 100 شخص إلى عدد السنوات، على التوالي. وارتبط الكوتريموكسازول بانخفاض في معدل الوفيات نسبته 37 % (نسبة المخاطر: 0.63؛ فاصل الثقة 95 %، فاصل الثقة: من0.56 إلى 0.70). وأدى استخدام الكوتريموكسازول بالإضافة إلى العلاج بمضادات الفيروسات القهقرية إلى تقليل معدل الوفيات بشكل كبير على مدار فترة المتابعة التي دامت 6 أشهر (نسبة المخاطر: 0.65؛ فاصل الثقة 95 %: من 0.59 إلى 0.73)، و12 شهراً (نسبة المخاطر: 0.58؛ فاصل الثقة 95 %: من 0.49 إلى 0.70)، و18 شهراً (نسبة المخاطر: 0.49؛ فاصل الثقة 95 %: من 0.38 إلى 0.63)، و24 شهراً (نسبة المخاطر: 0.66؛ فاصل الثقة 95 %: من 0.48 إلى 0.90). واتضح الانخفاض في معدل الوفيات بين المرضى الذين كانت إحصاءات الخلايا اللمفاوية التائية المساعدة (CD4+) عند خط الأساس لديهم أقل من 50 خلية/ميكرو لتر (نسبة المخاطر: 0.60؛ فاصل الثقة 95 %: من 0.54 إلى 0.67)، ومن 50 إلى 99 خلية/ميكرو لتر (نسبة المخاطر: 0.66؛ فاصل الثقة 95 %: من 0.56 إلى 0.78)، ومن 100 إلى 199 خلية/ميكرو لتر (نسبة المخاطر: 0.78؛ فاصل الثقة 95 %: من 0.62 إلى 0.98).. أدت الوقاية باستخدام الكوتريموكسازول التي تم بدأت في مرحلة مبكرة خلال العلاج بمضادات الفيروسات القهقرية إلى تقليل معدل الوفيات ومن ثم ينبغي توفيرها للمرضى المصابين بفيروس العوز المناعي البشري في البلدان المنخفضة الدخل والبلدان المتوسطة الدخل.. 评估抗逆转录病毒治疗（ART）早期进行磺胺甲基异恶唑预防疗法是否降低中国艾滋病病毒（HIV）感染成年人的死亡率。.. 我们使用中国国家免费抗逆转录病毒数据库的数据进行回顾性观察性队列研究。对14岁以上在2010年1月1日至2012年12月31日之间开始ART治疗并且基准CD4+T淋巴细胞（CD4+细胞）计数小200 cells/µL的患者进行跟踪随访，直至死亡、失访或到2013年12月31日。使用多元分析计算数个变量的风险比（HR）。.. 该分析涉及23816名艾滋病病毒感染者，其中2706人在随访期间死亡。在ART治疗前6个月开始接受或者未接受磺胺甲基异恶唑预防疗法的病人死亡率分别为每100人年5.3和7.0。磺胺甲基异恶唑预防疗法与死亡率降低37%（危害比、HR：0.63；95%置信区间，CI：0.56-0.70）相关。ART结合磺胺甲基异恶唑预防疗法显著降低持续6个月（HR：0.65；95% CI：0.59-0.73）、12个月（HR：0.58；95% CI：0.49-0.70）、18个月（HR：0.49；95% CI：0.38-0.63）和24个月（HR：0.66；95% CI：0.48-0.90）随访期间的死亡率。基准CD4+细胞计数小于50 cells/µL（HR：0.60；95% CI：0.54-0.67）、50-99 cells/µL（HR：0.66；95% CI：0.56-0.78）和100-199 cells/µL（HR：0.78；95% CI：0.62-0.98）的患者的死亡率降低明显。.. 在ART治疗早期加入磺胺甲基异恶唑预防疗法可降低死亡率，应为中低收入国家艾滋病病毒感染者提供此疗法。.. Определить, приводит ли профилактика котримоксазолом на раннем этапе антиретровирусной терапии (АРТ) к снижению смертности среди ВИЧ-инфицированных взрослых в Китае.. Было проведено ретроспективное обсервационное когортное исследование с использованием данных Китайской национальной базы данных свободного доступа по антиретровирусной терапии. Пациенты старше 14 лет, которые начали получать АРТ в период с 1 января 2010 года по 31 декабря 2012 года, и исходное число CD4+ T-лимфоцитов которых составляло менее 200 клеток/мкл, находились под наблюдением до летального исхода, выбытия из наблюдения или до 31 декабря 2013 года. С помощью многомерных анализов определялось отношение рисков (ОР) для нескольких переменных.. Анализ охватывал 23 816 ВИЧ-инфицированных пациентов, 2706 из которых скончались во время наблюдения. Уровень смертности среди пациентов, начавших и не начавших прием котримоксазола в течение первых 6 месяцев АРТ, составлял 5,3 и 7,0 на 100 человеко-лет соответственно. Котримоксазол ассоциировался с 37%‑ным снижением уровня смертности (отношение рисков (ОР): 0,63; 95%‑ный доверительный интервал (ДИ): 0,56-0,70). Котримоксазол в дополнение к АРТ значительно снижал смертность во время последующего наблюдения, длившегося 6 месяцев (ОР: 0,65; 95% ДИ: 0,59–0,73), 12 месяцев (ОР: 0,58; 95% ДИ: 0,49-0,70), 18 месяцев (ОР: 0,49; 95% ДИ: 0,38-0,63) и 24 месяца (ОР: 0,66; 95% ДИ: 0,48-0,90). Заметное снижение смертности наблюдалось у пациентов с исходным показателем CD4+ менее 50 клеток/мкл (ОР: 0,60; 95% ДИ: 0,54–0,67), 50–99 клеток/мкл (ОР: 0,66; 95% ДИ: 0,56–0,78) и 100–199 клеток/мкл (ОР: 0,78; 95% ДИ: 0,62-0,98).. Профилактика котримоксазолом, начатая на раннем этапе АРТ, приводила к снижению смертности и должна предлагаться ВИЧ-инфицированным пациентам в странах с низким и средним уровнями доходов.

Topics: Adult; Anti-Bacterial Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; China; Cohort Studies; Databases, Factual; Female; HIV Infections; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Predisposing factors of pyogenic odontogenic infection include dental caries, pericoronitis, periodontitis, trauma to the dentition and the supporting structures or complications of dental procedures. The infections are usually polymicrobial involving normal endogenous flora. We characterised pyogenic odontogenic infection in patients attending Mulago Hospital, Uganda.. Of the 130 patients, 62 (47.7%) were female. The most frequently involved fascial spaces were: the buccal, 52 (25.4%); submasseteric, 46 (22.4%) and the submandibular space, 36 (17.5%). Dental caries was the most prevalent predisposing factor, particularly of the lower third molar teeth. Viridans Streptococci Group and Staphylococcus aureus were the most frequent bacterial isolates: 23.5% and 19.4%, respectively. All Viridans Streptococci isolates were resistant to penicillin G, sulfamethoxazole/trimethoprim (cotrimoxazole), ampicillin and tetracycline, but susceptible to vancomycin. All Staphylococcus aureus strains were resistant to cotrimoxazole and ampicillin while retaining susceptibility to vancomycin, cefotaxime, linezolid, moxifloxacin and amoxicillin/clavulanate. Thirty five (26.9%) patients were HIV infected and the HIV status did not significantly influence the pattern of odontogenic infection.. Dental caries was the most prevalent predisposing factor for pyogenic odontogenic infection. High prevalence of bacterial resistance to ampicillin and cotrimoxazole suggests the need for regular antibiotic susceptibility tests of isolates and rational use of antibiotics in the management of these infections. Prevention requires strengthening of oral health in the community.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Child; Child, Preschool; Coinfection; Cross-Sectional Studies; Dental Caries; Drug Resistance, Multiple, Bacterial; Female; HIV; HIV Infections; Hospitals; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Periodontitis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Viridans Streptococci

Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown.. We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections.. CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics.. CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.

Topics: Antimalarials; Asymptomatic Infections; Drug Resistance; Female; HIV Infections; Humans; Infant; Malaria; Malawi; Male; Parasitemia; Plasmodium falciparum; Random Allocation; Trimethoprim, Sulfamethoxazole Drug Combination

Both darunavir (DRV) and trimethoprim-sulfamethoxazole (TMP-SMX) carry a sulfonamide moiety and a warning for this cross-reactivity is given in the label of DRV. The aim of this study was to investigate the potential cross-reactivity between both drugs.. Retrospective cohort study with a nested case-control study.. HIV-infected patients that received DRV-containing antiretroviral therapy at any time during the period of their HIV infection were included. Patients with no history of TMP-SMX use were excluded. The incidence of a DRV allergy, according to the Naranjo probability scale, was investigated in patients with an allergy to TMP-SMX compared with those without such an allergy. In order to identify possible risk factors associated with a DRV allergy among patients allergic to TMP-SMX, a nested case-control study was subsequently performed.. A total of 405 patients were included, of whom 79 (17.5%) had a history of allergy to TMP-SMX. A DRV allergy was seen in four patients (5.1%) with a TMP-SMX allergy compared with four (1.2%) without a TMP-SMX allergy (P = 0.05). Patients with a TMP-SMX allergy were at higher risk for a DRV allergy (odds ratio 4.29; 95% confidence interval, 1.05-17.56). No additional risk factors for a DRV allergy among patients allergic to TMP-SMX were identified in the nested case-control study.. Although DRV allergy is uncommon, making cross-reactivity with TMP-SMX a rare clinical problem, it appears to exist more often in the background of a TMP-SMX allergy.

Topics: Adult; Aged; Anti-HIV Agents; Anti-Infective Agents; Case-Control Studies; Cohort Studies; Darunavir; Drug Hypersensitivity; Drug Interactions; Female; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections.. This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence.. CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.

Topics: Adolescent; Adult; Animals; Anti-Retroviral Agents; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; Gabon; Helminthiasis; HIV Infections; Humans; Logistic Models; Loiasis; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Microbial translocation (MT) contributes to immune activation during HIV-1 infection, and persists after initiation of antiretroviral therapy (ART). We investigated whether levels of MT markers are influenced by the use of co-trimoxazole (TMP-SMX) in HIV-1 patients. Plasma samples were obtained from HIV-1-infected patients initiating ART with (n=13) or without (n=13) TMP-SMX prophylaxis. Markers of MT [lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP)] were assessed at baseline (BL), at 1 month, and at 1 year by the Limulus Amebocyte Lysate Assay or ELISA. BL levels of LBP were elevated in both categories of patients; they were highest in patients starting ART and TMP-SMX (median, μg/ml: 36.7 vs. 4.3, respectively, p=0.001) and correlated inversely with CD4(+) T cell counts (ρ=-0.65; p=0.005). Patients receiving ART and TMP-SMX had a significant reduction in LBP between BL and 1 year (median, μg/ml: 36.7 vs. 11.1; p=0.003). In contrast, levels of LPS at BL were lower in patients starting ART and TMP-SMX compared to those without TMP-SMX (median, pg/ml: 221 vs. 303 respectively; p=0.002) and did not change at 1 year. The increased BL levels of sCD14 had declined in both groups at 1 year. No difference in I-FABP levels was found between BL and 1 year. Concomitant use of ART and TMP-SMX reduces microbial translocation markers LBP and sCD14, probably due to its impact on the gut microbiota. Effective ART for 1 year does not restore gut-blood barrier dysfunction.

Topics: Acute-Phase Proteins; Adult; Aged; Animals; Anti-Bacterial Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Bacterial Translocation; Biomarkers; Carrier Proteins; Fatty Acid-Binding Proteins; Female; HIV Infections; HIV-1; Humans; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Membrane Glycoproteins; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have in vitro activity against Mycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40 Mycobacterium tuberculosis isolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

Topics: Adult; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Female; HIV Infections; Humans; Male; Mycobacterium tuberculosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Young Adult

To identify risk factors for loss to follow-up (LTFU) in an HIV-infected pediatric population in Dar es Salaam, Tanzania, between 2004 and 2011.. Longitudinal analysis of 6236 HIV-infected children.. We conducted a prospective cohort study of 6236 pediatric patients enrolled in care and treatment in Dar es Salaam from October 2004 to September 2011. LTFU was defined as missing a clinic visit for >90 days for patients on ART and for >180 days for patients in care and monitoring. The relationship of baseline and time-varying characteristics to the risk of LTFU was examined using a Cox proportional hazards model.. A total of 2130 children (34%) were LTFU over a median follow-up of 16.7 months (interquartile range, 3.4-36.9). Factors independently associated with a higher risk of LTFU were age ≤2 years (relative risk [RR] = 1.59, 95% CI: 1.40 to 1.80), diarrhea at enrollment (RR = 1.20, 95% CI: 1.03 to 1.41), a low mid-upper arm circumference for age (RR = 1.20, CI: 1.05 to 1.37), eating protein-rich foods ≤3 times a week (RR = 1.39, 95% CI: 1.05 to 1.90), taking cotrimoxazole (RR = 1.39, 95% CI: 1.06 to 1.81), initiating onto antiretrovirals (RR = 1.37, 95% CI: 1.17 to 1.61), receiving treatment at a hospital instead of a local facility (RR = 1.39, 95% CI: 1.06 to 1.41), and starting treatment in 2006 or later (RR = 1.10, 95% CI: 1.04 to 1.16).. Health workers should be aware of pediatric patients who are at a greatest risk of LTFU, such as younger and undernourished patients, so that they can proactively counsel families about the importance of visit adherence. Findings support decentralization of HIV care to local facilities as opposed to hospitals.

Topics: Anti-HIV Agents; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Dietary Proteins; Female; HIV Infections; Humans; Lost to Follow-Up; Male; Malnutrition; Risk Factors; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylaxis has an antimalarial effect which could have an additional protective effect against malaria in HIV-infected children on antiretroviral therapy (ART). We measured the incidence and associated factors of malaria in HIV-infected children on ART and/or cotrimoxazole in Abidjan, Côte d'Ivoire.. All HIV-infected children <16 years, followed-up in the IeDEA West-African paediatric cohort (pWADA) in Abidjan, were prospectively included from May to August 2012, the rainy season. Children presenting signs suggesting malaria had a thick blood smear and were classified as confirmed or probable malaria. We calculated incidence density rates (IR) per 100 child-years (CY). Risk factors were assessed using a Poisson regression model.. Overall, 1117 children were included, of whom 89 % were ART-treated and 67 % received cotrimoxazole. Overall, there were 51 malaria events occurring in 48 children: 28 confirmed and 23 probable; 94 % were uncomplicated malaria. The overall IR of malaria (confirmed and probable) was 18.3/100 CY (95 % CI: 13.3-23.4), varying from 4.2/100 CY (95 % CI: 1.1-7.3) in children on ART and cotrimoxazole to 57.3/100 CY (95 % CI: 7.1-107.6) for those receiving no treatment at all. In univariate analysis, age < 5 years was significantly associated with a 2-fold IR of malaria compared to age >10 years (incidence rate ratio [IRR] = 2.18, 95 % CI: 1.04-4.58). Adjusted for severe immunodeficiency, cotrimoxazole reduced significantly the IR of first malarial episode (adjusted IRR [aIRR] = 0.13, 95 % CI: 0.02-0.69 and aIRR = 0.05, 95 % CI:0.02-0.18 in those off and on ART respectively). Severe immunodeficiency increased significantly the malaria IR (aIRR = 4.03, 95 % CI: 1.55-10.47). When considering the IR of confirmed malaria only, this varied from 2.4/100 CY (95 % CI: 0.0-4.8) in children on ART and cotrimoxazole to 34.4/100 CY (95 % CI: 0.0-73.3) for those receiving no treatment at all. In adjusted analyses, the IR of malaria in children on both cotrimoxazole and ART was significantly reduced (aIRR = 0.05, 95 % CI: 0.01-0.24) compared to those receiving no treatment at all.. Cotrimoxazole prophylaxis was strongly protective against the incidence of malaria when associated with ART in HIV-infected children. Thus, these drugs should be provided as widely and durably as possible in all HIV-infected children <5 years of age.

Topics: Anti-HIV Agents; Antimalarials; Child; Child, Preschool; Cohort Studies; Cote d'Ivoire; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Male; Prospective Studies; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally. Of note, Zimbabwe also provided nevirapine prophylaxis for HIV exposed babies, so the majority were giving nevirapine and CTX-p to their babies.. Between Feb-Dec 2011, the first 20 HIV infected mothers identified were invited for in-depth interview 4-5months postnatally. Interviews were recorded, transcribed, translated and analysed thematically.. All women desired their baby's health above all else, and were determined to do all they could to ensure their wellbeing. They did not report problems remembering to give drugs. The baby's apparent good health was a huge motivator for continued adherence. However, most women reported that their husbands were less engaged in HIV care, refusing to be HIV tested and in some cases stealing drugs prescribed for their wives for themselves. In two instances the man stopped the woman from giving CTX-p to the baby either because of fear of side effects or not appreciating its importance. Stigma continues to be an important issue. Mothers reported being reluctant to disclose their HIV status to other people so found it difficult to collect prescription refills from the HIV clinic for fear of being seen by friends/relatives. Some women reported that it was hard to administer the drugs if there were people around at home. Other challenges faced were stock-outs of CTX-p at the clinic, which occurred three times in 2011. The baby would then go without CTX-p if the woman could not afford buying at a private pharmacy.. The study highlights that adherence knowledge and desire alone is insufficient to overcome the familial and structural barriers to maintaining CTX-p. Improving adherence to CTX-p among HEI will require interventions to improve male involvement, reduce HIV stigma in communities and ensure adequate supply of drugs.

Topics: Adult; Cross-Sectional Studies; Drug Combinations; Female; HIV Infections; Humans; Infant; Nevirapine; Post-Exposure Prophylaxis; Qualitative Research; Social Stigma; Trimethoprim, Sulfamethoxazole Drug Combination; Zimbabwe

Pneumocystis jirovecii is responsible for P. jirovecii pneumonia (PJP) in immunocompromised individuals, with a recent rise of cases noted in non-HIV patients. A middle-aged man presented with new-onset cough, fever, hypoxia and tachypnoea. He was on a tapering course of dexamethasone for amiodarone-induced thyrotoxicosis. He developed worsening airspace disease necessitating mechanical ventilation. Bronchoalveolar lavage (BAL) fluid was positive for P. jirovecii and he was managed with trimethoprim/sulfamethoxazole and pentamidine, but succumbed to cardiorespiratory arrest. One-third of PJP cases occur in non-HIV patients, and have a higher morbidity and mortality. Most immunocompromised patients typically exhibit PJP during a corticosteroid taper. The accurate dose, duration or frequency of steroid use in not well established. Diagnosis of PJP in this population is more challenging due to lower BAL yield with alternate modalities such as serum/BAL β-d-glucan and PCR enhancing the yield. Further studies are needed to highlight PJP prophylaxis in patients with steroid use.

Topics: Bronchoalveolar Lavage Fluid; Fatal Outcome; HIV Infections; Humans; Immunocompromised Host; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

As a result of successful PMTCT programs, children born from HIV-infected mothers are now effectively protected from contracting the infection. However, it is not well known whether in utero exposure to the virus and the subsequent exposure to Cotrimoxazole (CTX) prophylaxis affect the cell mediated immune system of the children. This observational prospective study was aimed at determining how CD4(+) T, CD8(+) T and B cell subsets varied in HIV-exposed but uninfected (HEU) children at different ages.. We recruited HEU and HIV-unexposed and uninfected (HUU) children from 6 months of age and followed them up until they were 18 months old. HEU children received daily CTX prophylaxis beginning at 6 weeks of age until when 12 months of age. Venous blood samples were collected 6 monthly and analysed for different subsets of CD8(+) T, B cells and totalCD4(+) T cells.. At 6 months of age, HEU children had a lower percentage of total CD4(+) T cells compared to HUU children and a lower proportion of naïve CD8(+) T cells but higher percentage of effector memory CD8(+) T cells compared to HUU children. HEU and HUU children had similar proportions of all B cell subsets at all ages.. The study showed that the subtle variations in CD4(+) and CD8(+) T cell subsets observed at 6 months do not last beyond 12 months of age, suggesting that HEU children have a robust cell-mediated immune system during first year of life.. This article report is not based on results of a controlled health-care intervention.

Topics: B-Lymphocyte Subsets; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Infant; Lymphocyte Count; Malawi; Trimethoprim, Sulfamethoxazole Drug Combination

Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin resistant Staphylococcus aureus among HIV-infected patients. Recurrent infections are frequent. Risk factors for recurrence after an initial SSTI have not been well-studied.. Retrospective cohort study, single center, 2005-2009. Paper and electronic medical records were reviewed by one of several physicians. Subjects with initial SSTI were followed until the time of SSTI recurrence. Standard descriptive statistics were calculated to describe the characteristics of subjects who did and did not develop a recurrent SSTI. Kaplan-Meier methods were used to estimate the risk of recurrent SSTI. A Cox regression model was developed to identify predictors of SSTI recurrence.. 133 SSTIs occurred in 87 individuals. 85 subjects were followed after their initial SSTI, of whom 30 (35.3 %) had a recurrent SSTI in 118.3 person-years of follow-up, for an incidence of second SSTI of 253.6 SSTIs/1000 person-years (95 % CI 166.8-385.7). The 1-year Kaplan-Meier estimated risk of a second SSTI was 29.2 % (95 % CI 20.3-41.0 %), while the 3-year risk was 47.0 % (95 % CI 34.4-61.6 %). Risk factors for recurrent SSTI in a multivariable Cox regression model were non-hepatitis liver disease (HR 3.44; 95 % CI 1.02-11.5; p = 0.05), the presence of an intravenous catheter (HR 6.50; 95 % CI 1.47-28.7; p = 0.01), and a history of intravenous drug use (IVDU) (HR 2.80; 95 % CI 1.02-7.65; p = 0.05); African-American race was associated with decreased risk of recurrent SSTI (HR 0.12; 95 % CI 0.04-0.41; p < 0.01). Some evidence was present for HIV viral load ≥ 1000 copies/mL as an independent risk factor for recurrent SSTI (HR 2.21; 95 % CI 0.99-4.94; p = 0.05). Hemodialysis, currently taking HAART, CD4+ count, trimethoprim-sulfamethoxazole or azithromycin use, initial SSTI type, diabetes mellitus, incision and drainage of the original SSTI, or self-report of being a man who has sex with men were not associated with recurrence.. Of HIV-infected patients with an SSTI, nearly 1/3 had a recurrent SSTI within 1 year. Risk factors for recurrent SSTI were non-hepatitis liver disease, intravenous catheter presence, a history of IVDU, and non-African-American race. Low CD4+ count was not a significant risk factor for recurrence.

Topics: Adult; Antiretroviral Therapy, Highly Active; Azithromycin; CD4 Lymphocyte Count; Cohort Studies; Coinfection; Female; HIV Infections; Humans; Kaplan-Meier Estimate; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Retrospective Studies; Risk Factors; Soft Tissue Infections; Staphylococcal Skin Infections; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

The HIV/AIDS health challenge continues to ravage many resource-constrained countries of the world. Approximately 75 % of all the global HIV/AIDS related deaths totaling 1.6 (1.4-1.9) million in 2012 occurred in sub-Saharan Africa, Uganda contributed 63,000 (52,000-81,000) to these deaths. Most of the morbidity and mortality associated with HIV/AIDS can be averted if individuals with HIV/AIDS have improved access to HIV care and treatment. The aim of this study therefore, was to explore the factors associated with access to HIV care services among HIV seropositive clients identified by a home based HIV counseling and testing program in Kumi district, eastern Uganda.. In a cross sectional study conducted in February 2009, we explored predictor variables: socio-demographics, health facility and community factors related to access to HIV care and treatment. The main outcome measure was reported receipt of cotrimoxazole for prophylaxis.. The majority [81.1 % (284/350)] of respondents received cotrimoxazole prophylaxis (indicating access to HIV care). The main factors associated with access to HIV care include; age 25-34 years (AOR = 5.1, 95 % CI: 1.5-17.1), male sex (AOR = 2.3, 95 % CI: 1.2-4.4), urban residence (AOR = 2.5, CI: 1.1-5.9) and lack of family support (AOR = 0.5, CI: 0.2-0.9).. There was relatively high access to HIV care and treatment services at health facilities for HIV positive clients referred from the Kumi home based HIV counseling and testing program. The factors associated with access to HIV care services include; age group, sex, residence and having a supportive family. Stakeholders involved in providing HIV care and treatment services in similar settings should therefore consider these socio-demographic variables as they formulate interventions to improve access to HIV care services.

Topics: Adolescent; Adult; Age Factors; AIDS Serodiagnosis; Anti-Infective Agents; Counseling; Cross-Sectional Studies; Family; Female; Health Services Accessibility; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Sex Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Bacterial Infections; Darunavir; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading independent global causes of death among patients with infectious diseases. Additionally, due to the shared immune defense mechanisms, they are the leading cause of co-morbidities globally. However, little information was found regarding the proportion of TB/HIV co-infection in the study area. Thus, this study determined the proportion and associated factors of TB/HIV co-infection.. All TB patients treated from January/2011 to December/2014 were included in this study. Data were collected from three health centers namely; Kobo, Robit and Gobiye. Data were entered, cleared, and analyzed using SPSS version 20. Frequency, percentage, median and range were used to present the data. To assess the associated factors, logistic regression was employed.. Of the total 990 TB patients enrolled in the study, 98.2 % were screened for HIV; of these, 24.3 % were co-infected with TB and HIV. The odds of having TB/HIV co-infection were 3.4 times higher among in the age group of 25-45 years compared to older (≥45 years) age TB patients (OR = 3.4; 95 % CI 2-5). Moreover, the odds of having TB/HIV co-infection were 2.8 and 1.7 times higher among smear positive and smear negative patients with pulmonary TB respectively than patients with extra pulmonary TB. Of 236 co-infected patients, 71.2 % took co-trimoxazole preventive therapy and 76.3 % took antiretroviral treatment.. TB/HIV co-infection is one of the serious public health problems in the study area. Thus, Collaborative TB/HIV activities that reduce the co-morbidities and mortalities should be addressed.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Retroviral Agents; Child; Child, Preschool; Coinfection; Comorbidity; Ethiopia; Female; HIV Infections; Humans; Infant; Logistic Models; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Nigeria has a high burden of children living with HIV and tuberculosis (TB). This article examines the magnitude of TB among children receiving antiretroviral treatment (ART), compares their ART outcomes with their non-TB counterparts and argues that addressing TB among children on ART is critical for achieving the 90-90-90 targets.. This was a facility-based, retrospective analysis of medical records of children aged <15 years who were newly initiated on ART between 2011 and 2012. Structured tools were used to collect data. STATA software was used to perform descriptive, survival and multivariate analyses.. A total of 1142 children with a median age of 3.5 years from 20 selected facilities were followed for 24 months. Of these, 95.8% were assessed for TB at ART initiation and 14.7% had TB. Children on ART were more likely to have TB if they were aged 5 years or older (p<0.01) and had delayed ART initiation (p<0.05). The cotrimoxazole and isoniazid prophylaxes were provided to 87.9 and 0.8% of children, respectively. The rate of new TB cases was 3 (2.2-4.0) per 100 person-years at six months and declined to 0.2 (0.06-1.4) per 100 person-years at 24 months. TB infection [adjusted hazard ratio (aHR): 4.3; 2.3-7.9], malnutrition (aHR: 5.1; 2.6-9.8), delayed ART initiation (aHR: 3.2; 1.5-6.7) and age less than 1 year at ART initiation (aHR: 4.0; 1.4-12.0) were associated with death. Additionally, patients with TB (aHR: 1.3; 1.1-1.6) and children below the age of 1 at ART initiation (aHR: 2.9; 1.7-5.2) were more likely to be lost to follow-up (LFU).. Children on ART with TB are less likely to survive and more likely to be LFU. These risks, along with low isoniazid uptake and delayed ART initiation, present a serious challenge to achieving the 90-90-90 targets and underscore an urgent need for inclusion of childhood TB/HIV in global plans and reporting mechanisms.

Topics: Adolescent; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Coinfection; HIV Infections; Humans; Infant; Lost to Follow-Up; Male; Nigeria; Proportional Hazards Models; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Malaria and HIV/AIDS constitute major public health problems in Ethiopia, but the burden associated with malaria-HIV co-infection has not been well documented. In this study, the burden of malaria among HIV positive and HIV negative adult outpatients attending health facilities in Oromia National Regional State, Ethiopia was investigated.. A comparative cross-sectional study among HIV-positive patients having routine follow-up visits at HIV care and treatment clinics and HIV-seronegative patients attending the general medical outpatient departments in 12 health facilities during the peak malaria transmission season was conducted from September to November, 2011. A total of 3638 patients (1819 from each group) were enrolled in the study. Provider initiated testing and counseling of HIV was performed for 1831 medical outpatients out of whom 1819 were negative and enrolled into the study. Malaria blood microscopy and hemoglobin testing were performed for all 3638 patients. Data was analyzed using descriptive statistics, Chi square test and multivariate logistic regression.. Of the 3638 patients enrolled in the study, malaria parasitaemia was detected in 156 (4.3%); malaria parasitaemia prevalence was 0.7% (13/1819) among HIV-seropositive patients and 7.9% (143/1819) among HIV-seronegative patients. Among HIV-seropositive individuals 65.4% slept under a mosquito bed net the night before data collection, compared to 59.4% of HIV-seronegative individuals. A significantly higher proportion of HIV-seropositive malaria-negative patients were on co-trimoxazole (CTX) prophylaxis as compared to HIV-malaria co-infected patients: 82% (1481/1806) versus 46% (6/13) (P = 0.001). HIV and malaria co-infected patients were less likely to have the classical symptoms of malaria (fever, chills and headache) compared to the HIV-seronegative and malaria positive counterparts. Multivariate logistic regression showed that HIV-seropositive patients who come for routine follow up were less likely to be infected by malaria (OR = 0.23, 95% CI = 0.09-0.74).. The study documented lower malaria prevalence among the HIV-seropositive attendants who come for routine follow up. Clinical symptoms of malaria were more pronounced among HIV-seronegative than HIV-seropositive patients. This study also re-affirmed the importance of co-trimoxazole in preventing malaria symptoms and parasitaemia among HIV-positive patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Chemoprevention; Coinfection; Cross-Sectional Studies; Ethiopia; Female; HIV Infections; Humans; Malaria; Male; Middle Aged; Outpatients; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Adolescent; Anti-HIV Agents; Child; Democratic Republic of the Congo; Developing Countries; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Hospitals, University; Humans; Infectious Disease Transmission, Vertical; Male; Medication Adherence; Risk Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Female; HIV Infections; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Trimethoprim, Sulfamethoxazole Drug Combination

Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region.. We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status.. In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality.. In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis.

Topics: Adult; Female; HIV Infections; Humans; Longitudinal Studies; Male; Risk Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa.. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings.. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up.. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

Topics: Adolescent; Adult; Anti-Infective Agents; Coinfection; Cross-Sectional Studies; Ethiopia; Female; Follow-Up Studies; Health Surveys; HIV Infections; Humans; Male; Mass Screening; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Drug use evaluation is a performance improvement method that focuses on evaluating and improving drug use process to achieve optimal patient outcomes. Drug use evaluation helps in identifying, preventing or resolving actual and potential drug related problems. The objective of the study was to evaluate the use of cotrimoxazole as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital, Northeast Ethiopia.. A retrospective drug use evaluation was conducted on patients' medical history records based on a validated drug use evaluation criteria according to the national guideline. Medical history records of 248 patients were selected using systematic sampling method.. The result showed that 49.6% of the patients were at WHO clinical stage III at the start of cotrimoxazole preventive therapy. In this study, the use of cotrimoxazole preventive therapy was consistent with the guideline in the rationale for indication (97.98%), dose (96.77%), and its use despite the presence of contraindications (91.93%). Problems regarding drug-drug interaction were identified in 49.59% of cases, and 20.97% of patients discontinued cotrimoxazole preventive therapy due to different reasons.. In most patients cotrimoxazole preventive therapy was consistent with the national guideline regarding the rationale for indication, dose, discontinuation and its use in the presence of contraindications.

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Drug Interactions; Drug Utilization; Ethiopia; HIV Infections; Hospitals, Rural; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

An evidence-based basic care package (BCP) of seven interventions (Family testing, Cotrimoxazole, Condoms, Multivitamins, Access to safe water treatment, Isoniazid preventive therapy (IPT), and Insecticide-treated bednet) has been advocated to prevent infections among people with HIV in low-income settings. We examined the availability and receipt of the BCP in HIV outpatient clinics in Kenya and Uganda. A survey of 120 PEPFAR-funded facilities determined the services offered. At each of the 12 largest facilities, a longitudinal cohort of 100 patients was recruited to examine care received and health status over three months. The full BCP was offered in 14% (n = 17/120) of facilities; interventions most commonly offered were Support for family testing (87%) and Condoms (87%), and least commonly IPT (38%). Patients (n = 1335) most commonly reported receiving Cotrimoxazole (57%) and Multivitamins (36%), and least commonly IPT (4%), directly from the facility attended. The BCP (excluding Isoniazid) was received by 3% of patients directly from the facility and 24% from any location. BCP receipt was associated with using antiretroviral therapy (ART; OR 1.1 (95% CI 1.0-1.1), receipt from any location) but not with patient gender, wealth, education level or health. The BCP should be offered at more HIV care facilities, especially Isoniazid, and to more people irrespective of ART use. Coordinating local BCP suppliers could help improve availability through addressing logistical challenges or reducing costs.

Topics: Adolescent; Adult; Anti-Infective Agents; Communicable Disease Control; Condoms; Cross-Sectional Studies; Evidence-Based Medicine; Female; HIV Infections; Humans; Insecticide-Treated Bednets; Interviews as Topic; Isoniazid; Kenya; Longitudinal Studies; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Vitamins; Water Supply

Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

Topics: Adult; Anti-Retroviral Agents; Coinfection; Female; HIV Infections; Humans; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 µg.hr(-1) cm(-2)) and distal colon (-0.30±0.08 µg.hr(-1) cm(-2)). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr(-1) cm(-2)) or distal colon (+0.04±0.01 µg.hr(-1) cm(-2)). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy.

Topics: Administration, Oral; Analysis of Variance; Animals; Anti-Retroviral Agents; Atazanavir Sulfate; Biological Availability; Colon; Electric Conductivity; HIV Infections; Intestinal Absorption; Male; Metronidazole; Oligopeptides; Pyridines; Rats; Rats, Sprague-Dawley; Ritonavir; Trimethoprim, Sulfamethoxazole Drug Combination

Blood-stream infection (BSI) is one of the principle determinants of the morbidity and mortality associated with advanced HIV infection, especially in sub-Saharan Africa. Over the last 10 years, there has been rapid roll-out of anti-retroviral therapy (ART) and cotrimoxazole prophylactic therapy (CPT) in many high HIV prevalence African countries.. A prospective cohort of adults with suspected BSI presenting to Queen's Hospital, Malawi was recruited between 2009 and 2010 to describe causes of and outcomes from BSI. Comparison was made with a cohort pre-dating ART roll-out to investigate whether and how ART and CPT have affected BSI. Malawian census and Ministry of Health ART data were used to estimate minimum incidence of BSI in Blantyre district.. 2,007 patients were recruited, 90% were HIV infected. Since 1997/8, culture-confirmed BSI has fallen from 16% of suspected cases to 10% (p<0.001) and case fatality rate from confirmed BSI has fallen from 40% to 14% (p<0.001). Minimum incidence of BSI was estimated at 0.03/1000 years in HIV uninfected vs. 2.16/1000 years in HIV infected adults. Compared to HIV seronegative patients, the estimated incidence rate-ratio for BSI was 80 (95% CI:46-139) in HIV-infected/untreated adults, 568 (95% CI:302-1069) during the first 3 months of ART and 30 (95% CI:16-59) after 3 months of ART.. Following ART roll-out, the incidence of BSI has fallen and clinical outcomes have improved markedly. Nonetheless, BSI incidence remains high in the first 3 months of ART despite CPT. Further interventions to reduce BSI-associated mortality in the first 3 months of ART require urgent evaluation.

Topics: Adult; Anti-HIV Agents; Bacteremia; Coinfection; Female; HIV Infections; Hospitals, Municipal; Humans; Incidence; Malawi; Male; Middle Aged; Prospective Studies; Risk Factors; Salmonella Infections; Sex Distribution; Streptococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Diagnosis, Differential; Dyspnea; Female; Fever; HIV Infections; HIV-1; Humans; Lung; Oxygen; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Sweating; Trimethoprim, Sulfamethoxazole Drug Combination

Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6-8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them.. In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012.. Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01).. End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for selected high-risk groups.

Topics: Adult; Anti-HIV Agents; Antitubercular Agents; CD4 Lymphocyte Count; Coinfection; Female; HIV; HIV Infections; Hospitalization; Humans; Male; Middle Aged; Mycobacterium tuberculosis; Nigeria; Retrospective Studies; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant

In Kenya, mathematical models estimate that there are approximately 220,000 children aged less than 15 years infected with HIV. We analyzed data from the second Kenya AIDS Indicator Survey (KAIS 2012) to estimate the prevalence of HIV infection among children aged 18 months to 14 years.. KAIS 2012 was a nationally representative 2-stage cluster sample household survey. We studied children aged 18 months to 14 years whose parents or guardians answered questions pertaining to their children by interview. Blood specimens were collected for HIV serology and viral load measurement.. We identified 5162 children who were eligible for the study. Blood was obtained for 3681 (71.3%) children. Among child participants, 16.4% had been tested for HIV infection in the past, and among children with parents or guardians who self-reported HIV-positive status, 52.9% had been tested for HIV infection. Twenty-eight (0.9%) children tested HIV-positive in the survey. Of these, 11 had been previously diagnosed with HIV infection before the survey. All 11 children were in HIV care and receiving cotrimoxazole; 8 were on antiretorivral therapy (ART). Among those on ART, 4 were virologically suppressed.. HIV causes a substantial burden of disease in the Kenyan pediatric population. Although most children who had been diagnosed with HIV before the survey were engaged in care and treatment, they represented less than half of HIV-infected children identified in the survey. Future efforts should focus on identifying infected children and getting them into care and on suppressive ART as early as possible.

Topics: Adolescent; Age Factors; AIDS Serodiagnosis; Anti-Infective Agents; Anti-Retroviral Agents; Child; Child, Preschool; Cross-Sectional Studies; Female; Health Surveys; HIV Infections; Humans; Infant; Kenya; Male; Prevalence; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Population; Viral Load

Increasing access to care and treatment for HIV-infected persons is a goal in Kenya's response to the HIV epidemic. Using data from the second Kenya AIDS Indicator Survey (KAIS 2012), we describe coverage of services received among adults and adolescents who were enrolled in HIV care.. KAIS 2012 was a population-based survey that collected information from persons aged 15-64 years that included self-reported HIV status, and for persons reporting HIV infection, use of HIV care and antiretroviral therapy (ART). Blood specimens were collected and tested for HIV. HIV-positive specimens were tested for CD4 counts and viral load.. Among 363 persons who reported HIV infection, 93.4% [95% confidence interval (CI): 87.2 to 99.6] had ever received HIV care. Among those receiving HIV care, 96.3% (95% CI: 94.1 to 98.4) were using cotrimoxazole prophylaxis, and 74.6% (95% CI: 69.0 to 80.2) were receiving ART. A lower proportion of persons in care and not on ART reported using cotrimoxazole (89.5%, 95% CI: 82.5 to 96.5 compared with 98.6%, 95% CI: 97.1 to 100) and had a CD4 count measurement done (72.9%, 95% CI: 64.0 to 81.9 compared with 90.0%, 95% CI: 82.8 to 97.3) than persons in care and on ART, respectively. Among persons in care and not on ART, 23.2% (95% CI: 6.8 to 39.7) had CD4 counts ≤350 cells per microliter. Viral suppression was observed in 75.3% (95% CI: 68.7 to 81.9) of persons on ART.. Linkage and retention in care are high among persons with known HIV infection. However, improvements in care for the pre-ART population are needed. Viral suppression rates were comparable to developed settings.

Topics: Adolescent; Adult; Age Factors; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Cross-Sectional Studies; Educational Status; Female; Health Surveys; HIV Infections; Humans; Kenya; Male; Marital Status; Middle Aged; Patient Acceptance of Health Care; Sex Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy.. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis.. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95% CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95% CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy.. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women.

Topics: Adult; Anemia; Anti-Infective Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; Hemoglobins; HIV Infections; Humans; Malaria; Pregnancy; Prevalence; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jirovecii (former carinii) pneumonia, is a life-threatening opportunistic infection occurring in immunocompromised hosts. The aim of this study was to investigate the predisposing factors, clinical features and outcome of Pneumocystis pneumonia (PCP) in HIV-negative patients. The medical records of 62 adult patients with PCP, hospitalized at the University Hospital of Heraklion, Crete, Greece during a 10-year period (2004-2013) were retrospectively reviewed. All patients were immunosuppressed prior to the development of PCP. Thirty one patients (50%) suffered malignant hematological disease, 16 (26%) solid tumor and 15 (24%) had chronic inflammatory disease. Only 17 (27%) had received long-term systemic corticosteroids. All had symptoms of pneumonia upon admission, while 12 (19%) were suffering respiratory failure. Twenty one (34%) had received trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis before the PCP onset. Eight patients (13%) were admitted to the ICU. Mortality attributable to PCP reached 29%. Mortality attributable to PCP was higher in patients with solid tumors. TMP-SMX prophylaxis failed in a significant portion of the present cohort. Hence, PCP should be included in the differential diagnosis in immunocompromised patients with symptoms from the respiratory tract even if TMP-SMX has been given as prophylaxis.

Topics: Aged; Causality; Female; Greece; HIV Infections; Humans; Immunocompromised Host; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Female; HIV Infections; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Female; HIV Infections; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Trimethoprim, Sulfamethoxazole Drug Combination

Among human immunodeficiency virus (HIV)-infected adults and children in Africa, diarrheal disease remains a major cause of morbidity and mortality. We evaluated the effectiveness of provision and home-based reinforcement of a point-of-use water filtration device to reduce diarrhea among 361 HIV-infected adults in western Kenya by comparing prevalence of self-reported diarrhea before and after these interventions. After provision of the filter, 8.7% of participants reported diarrhea compared with 17.2% in the 3 months before filter provision (odds ratio [OR] = 0.39, 95% confidence interval [95% CI] = 0.23-0.66, P < 0.001). The association was similar among 231 participants who were already taking daily cotrimoxazole prophylaxis before being given a filter (OR = 0.47, 95% CI = 0.25-0.88, P = 0.019). Educational reinforcement was also associated with a modest reduction in self-reported diarrhea (OR = 0.50, 95% CI = 0.20-0.99, P = 0.047). Provision and reinforcement of water filters may confer significant benefit in reducing diarrhea among HIV-infected persons, even when cotrimoxazole prophylaxis is already being used.

Topics: Adult; Anti-Infective Agents; Coinfection; Diarrhea; Drinking Water; Female; Filtration; HIV; HIV Infections; Humans; Kenya; Male; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Water Purification

TB and HIV interaction increases TB incidence and HIV adverse outcomes. Integration improves patients' access to comprehensive care. This paper compares the impact of increasing integration on TB/HIV service delivery.. Three hospitals with different delivery models were identified and a survey of TB cases registered between June 2007 and December 2008 conducted. HIV screening, co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) uptake for HIV-positive TB patients were compared.. Of the 590 TB patients, 85.9% (507/590) knew their HIV status. HIV screening was highest (98.6% [95%CI: 97.6-99.5%]) at the one-stop shop (OSS) and lowest (72.5% [71.9-73.9%]) at the referral site (RS). CPT was highest [(93.8% [91.0-96.7%]) at the RS and least (74.7% [72.8-76.5%]) at the partially-integrated site (PIS). At the OSS it was 82.3% (80.6-84.0%). ART was highest (59.5% [58.0-61.0%]) at the PIS, and 10.8% (10.4-11.1%) at the RS. No ART records existed at the OSS.. Increasing integration improved HIV screening but not CPT or ART uptake. There was insufficient evidence to identify the most effective model due to design limitations and health system barriers. More research and training is needed to improve uptake, data completeness and accuracy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Child; Child, Preschool; Coinfection; Delivery of Health Care, Integrated; Female; Ghana; Health Policy; Health Services Accessibility; Health Services Needs and Demand; Health Services Research; HIV Infections; Humans; Incidence; Male; Mass Screening; Middle Aged; Public Health; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Anti-Infective Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Drug Interactions; Female; Fluconazole; Gene Expression; HIV; HIV Infections; Humans; Isoenzymes; Liver; Male; Middle Aged; Multivariate Analysis; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Single Nucleotide; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To demonstrate the effectiveness of quality improvement methods to monitor and improve administration of cotrimoxazole (CTX) prophylaxis to improve health outcomes among adults living with HIV/AIDS in low resource countries.. Program evaluation.. HIV/AIDS health care facilities in Uganda, Mozambique, Namibia and Haiti.. Performance measures based on national guidelines are developed in each country. These may include CD4 monitoring, ART adherence and uptake of CTX prophylaxis. CTX prophylaxis is routinely selected, because it has been shown to reduce HIV-related morbidity and mortality. Patient records are sampled using a standard statistical table to achieve a minimum confidence interval of 90% with a spread of ±8% in participating clinics. If an electronic medical record is available, all patients are reviewed. Routine review of performance measures, usually every 6 months, is conducted to identify gaps in care. Improvement interventions are developed and implemented at health facilities, informed by performance results, and local/national public health priorities.. Median clinic rates of CTX prophylaxis.. Median performance rates of CTX prophylaxis generally improved for adult HIV+ patients between 2006 and 2013 across countries, with median clinic rates higher than baseline at follow-up in 16 of 18 groups of clinics implementing CTX -focused improvement projects.. Quality management offers a data-driven method to improve the quality of HIV care in low resource countries. Application of improvement principles has been shown to be effective to increase the rates of CTX prophylaxis in national HIV programs in multiple countries.

Topics: Acquired Immunodeficiency Syndrome; Africa South of the Sahara; Anti-Bacterial Agents; Antibiotic Prophylaxis; Developing Countries; Guideline Adherence; Haiti; HIV Infections; Humans; Practice Guidelines as Topic; Quality Improvement; Trimethoprim, Sulfamethoxazole Drug Combination

This study aims to evaluate the effect of co-trimoxazole (CTX) prophylaxis on mortality reduction among HIV-infected patients receiving antiretroviral therapy (ART) in Henan Province, China.. We conducted a retrospective study.. All individuals aged 15 years and older who initiated ART between 2008 and 2010 in Henan Province with completed CTX prophylaxis treatment information were included. The effect of CTX prophylaxis was estimated using Kaplan-Meier survival analysis and multivariate Cox proportional hazard modeling for mortality at 3-months and 12-months after ART initiation.. Overall mortality among patients receiving both ART and CTX was nearly double at 3-months after ART initiation compared with that at 12-months (12.4 per 100 PY vs 6.3 per 100 PY, p < 0.01). After adjusting for gender, age, TB history, year of ART initiation and CD4 count at ART initiation, CTX was associated with a significant reduction in 12-month mortality (adjusted hazard ratio (AHR) = 0.65, 95% confidence interval (CI): 0.44-0.95; p = 0.027) compared with persons not receiving CTX. The protective effect was more pronounced in the first 3 months after ART initiation (AHR = 0.53, 95% CI: 0.32-0.89; p = 0.017).. CTX prophylaxis together with ART reduced mortality of adult HIV patients during the first 12 months of ART in Henan Province, China. The effect was highest in the first 3 months of ART. CTX should be prescribed to all HIV-infected adults who initiate ART.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; China; Female; HIV Infections; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Trimethoprim/sulfamethoxazole (TMP/SMX) is the recommended first-line treatment for human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP).However, in June 2010, the lone manufacturer of intravenous (IV) TMP/SMX in the United States stopped production of this medication. . To (a) evaluate the impact of the national IV TMP/SMX shortage on PJP treatment outcomes between 2 groups of HIV-infected patients-those treated before the shortage and those after the shortage-and (b) compare the length of hospital stay (LOS) and PJP treatment used before and after the shortage.. A retrospective, quasi-experimental study examining 2 groups of HIV-infected adult patients with PJP was performed at an academic medical center from September 1, 2008, to June 30, 2012. Patients treated when IV TMP/SMX was available, or preshortage (PRE), were compared with patients treated when IV TMP/SMX was not available, or postshortage (POST).PRE included patients treated between September 1, 2008, and May 30, 2010, and POST included patients treated between June 1, 2010, and June 30, 2012.  . Thirty-six patients were included in the study, 18 in each group. Treatment failure, the primary outcome, included mortality or worsening clinical status (WCS) after at least 5 days of therapy. Three patients in PRE (16.7%) and 6 patients in POST (33.3%) experienced treatment failure (P = 0.248). No patients in PRE and 3 patients in POST (16.7%) experienced WCS (P = 0.035). Three patients in each group expired.In POST, 5 of the 6 treatment failures (83.3%) occurred during the first 6 months of the shortage. Median (interquartile range) LOS was 11 days (7-17) in PRE and 14 days (5-22) in POST (P = 0.800).In PRE, 7 patients (38.9%) were initiated on oral PJP treatment compared with 13 (72.2%) in POST (P = 0.042). . The national shortage of IV TMP/SMX may have led to an immediate but temporary negative impact on treatment outcomes among HIV-infected patients with PJP at an academic medical center.Pharmacist collaboration with physicians may have helped mitigate the impact of this drug shortage on patient outcomes.  

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Therapy, Combination; Female; HIV Infections; Humans; Infusions, Intravenous; Male; Medical Records; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; United States

To document the prevalence of malaria parasitaemia among the HIV infected febrile children in a malaria endemic area.. A cross-sectional study.. An ambulatory paediatric HIV clinic in Western Kenya, between November 2011 and December 2012.. A total of 245 febrile HIV infected children aged less than 14 years attending the HIV clinic in the Webuye level IV hospital were included in the study. A systematic sampling method was used.. A blood sample was taken for malaria parasite testing. Presence or absence of malaria parasites was documented. Clinical and socio-demographic characteristics of the participants were also recorded.. A total of 245 participants were recruited mean age being 5.53 years. Malaria prevalence was 81.9%. Most participants (97%) were on cotrimoxazole prophylaxis. Some of the factors found to be positively associated with malaria parasitaemia were; male sex, care taker category (parent), WHO stage 3 and 4 of HIV disease, and a high absolute CD4 count. However, only the caretaker association was statistically significant.. The frequency of malaria parasitaemia among febrile HIV infected children is still high regardless of the high cotrimoxazole prophylaxis uptake. It is also noted that there is a shift in the age group of fever among children toward the older age group. This implies that policies may need to be relooked at to include the older age group in the aggressive malaria prevention measures to avoid losing on the already made gains.

Topics: Antimalarials; CD4 Lymphocyte Count; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Endemic Diseases; Female; Fever; HIV Infections; Humans; Infant; Malaria; Male; Parasitemia; Prevalence; Standard of Care; Trimethoprim, Sulfamethoxazole Drug Combination

More than 90% of cases of pneumocystis pneumonia (PCP) in adults occur in patients with chronic HIV infection with CD4 counts lower than 200 cells/ml. Even though primary HIV infection can cause transient profound CD4 lymphocytopenia, PCP is rarely reported during primary HIV infection. We report a case of a 26-year-old man who was diagnosed with PCP in the setting of primary HIV infection. He was successfully treated with a 21-day course of oral co-trimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns.. This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available.. A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole.. Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Botswana; Ciprofloxacin; Comorbidity; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Nitrofurantoin; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

A 46 years old HIV reactive patient developed Stevens Johnson syndrome (SJS) probably due to nevirapine and/or co-trimoxazole. Patient was on zidovudine + lamivudine + nevirapine along with Co-trimoxazole since last two months. After 15 days, zidovudine was replaced with stavudine due to development of anemia. All these drugs were stopped after development of reaction. Temporal association was found between stavudine, lamivudine, nevirapine, cotrimoxazole and development of the reaction. Nevirapine and Co-trimoxazole were suspected to cause this reaction most probably due to associated hepatotoxicity and their common potential to cause SJS. In our case, patient died despite stopping of all medications.

Topics: Anti-HIV Agents; Anti-Infective Agents; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Nevirapine; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa.. In a cross-sectional study of HIV-exposed infants 6-18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother.. One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5-57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily.. A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be seen as missed opportunities for early infant diagnosis of HIV and related care.

Topics: Antibiotic Prophylaxis; Child; Female; HIV Infections; Humans; Infant; Male; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Stevens-Johnson syndrome (SJS) can be a severe and life-threatening reaction with many potential causes, including multiple medications used in HIV care and treatment. Specific risk factors, especially in children, are not currently well-understood.. We describe a series of cases of SJS that occurred from 2006 to 2010 in an HIV-focused clinic in Mbabane, Swaziland. The electronic medical and pharmacy records of all pediatric patients <20 years old were reviewed to identify cases of SJS. Patient demographic, immunosuppression and outcome data were also collected.. A total of 19 cases of SJS were documented. Eighty-four percent of cases were attributed to nevirapine (NVP) exposure whereas the remaining cases were caused by cotrimoxazole (11%) and efavirenz (5%). Median symptom onset was 22 days after initiation of the offending medication (interquartile range = 14-25 days). At time of SJS, 84% had advanced or severe immunosuppression. Forty-two percent of patients required hospitalization, and no SJS-associated deaths were known to occur. Use of efavirenz was attempted in 8 NVP-associated cases after SJS resolution and was successful in all except 1.. SJS occurrence was rare in this population, with the majority of cases being associated with NVP. All occurred within 32 days of medication initiation, providing a target window for intensified monitoring and anticipatory guidance. SJS can occur in children at any age, with any level of immunosuppression, and can occur during the lead-in dosing period of NVP.

Topics: Adolescent; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Child; Child, Preschool; Cyclopropanes; Eswatini; Female; HIV Infections; Hospitalization; Humans; Infant; Male; Nevirapine; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Primary HIV infection can occur in 40-90% of individuals recently infected with HIV. Variable symptoms usually suggestive of a flu-like illness as well as high-level HIV viraemia and steep decline in CD4 cell count are often noted. We report a case of a previously healthy homosexual man who presented with symptoms suspicious of primary HIV infection as well as non-productive cough associated with chest CT finding of diffuse ground glass appearance in lungs. Recent HIV seroconversion was confirmed. Diagnosis of Pneumocystis jirovecii pneumonia was made on transbronchial lung biopsy. The symptoms improved rapidly after initiation of treatment with trimethoprim-sulfamethoxazole. It is important to recognise that although Pneumocystis pneumonia is generally seen in the setting of AIDS, it can occasionally also occur during primary HIV infection.

Topics: AIDS-Related Opportunistic Infections; Diagnosis, Differential; HIV Infections; HIV Seropositivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Private and public tuberculosis (TB) treatment centres in Lagos State, Nigeria.. To assess the contribution of private health care providers to TB and TB-HIV (human immunodeficiency virus) case finding in Lagos State.. A retrospective review of programme data submitted to the Lagos State TB and Leprosy Control Programme in 2011 by public, private for-profit (PFP) and private not-for-profit (PNFP) health care providers.. A total of 8425 TB cases were notified by 31 private (11 PFP and 20 PNFP) and 99 public health facilities in Lagos State. Overall, the private facilities were responsible for 10.3% (866/8425) of the total TB cases notified. The proportion of TB patients tested for HIV was respectively 86.2%, 53.1% and 96.5% among public, PFP and PNFP facilities. Overall, 22.4% of the TB patients were HIV-positive. The HIV positivity rate among public, PFP and PNFP facilities was respectively 23.8%, 7.8% and 9.9%. Uptake of cotrimoxazole preventive therapy was respectively 69.6%, 25% and 38.2% among public, PFP and PNFP facilities, while that of antiretroviral therapy was respectively 23.8%, 8.3% and 9.1% in public, PFP and PNFP facilities.. There is a need to scale up collaboration with the private sector, and particularly PNFP health providers.

Topics: Anti-HIV Agents; Antitubercular Agents; Coinfection; Cooperative Behavior; Delivery of Health Care, Integrated; Directly Observed Therapy; Disease Notification; HIV Infections; Hospitals, Proprietary; Hospitals, Voluntary; Humans; Interinstitutional Relations; Nigeria; Practice Patterns, Physicians'; Private Sector; Public Health; Public-Private Sector Partnerships; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Urban Health Services

Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.. We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana.. A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93).. Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

Topics: Anemia; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Infant; Neutropenia; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin.. The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities.. The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Topics: Anti-HIV Agents; Antitubercular Agents; Benin; Coinfection; Cooperative Behavior; Counseling; Delivery of Health Care, Integrated; Health Services Accessibility; Health Services Needs and Demand; HIV Infections; Humans; Interdisciplinary Communication; Interinstitutional Relations; Patient Acceptance of Health Care; Predictive Value of Tests; Program Development; Program Evaluation; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Benin, where 20 of 54 tuberculosis (TB) clinics caring for 80% of all TB patients began providing integrated human immunodeficiency virus (HIV) care in 2005.. To describe the characteristics and TB treatment outcomes of the first cohorts of TB-HIV patients, and to assess programmatic outcomes.. Retrospective cohort study using data from the TB register and the register of co-infected patients.. During the study period, 8368 TB patients were registered, 7787 (93%) were tested for HIV and 1255 (16%) were HIV-positive, including 385 (32%) who already knew their positive status. Most patients (88%) were tested within 15 days of TB diagnosis. Female and young patients were overrepresented among the co-infected. Cotrimoxazole preventive therapy was administered to 1152 patients (95%) during anti-tuberculosis treatment, and antiretroviral treatment (ART) to 469 (42%). The likelihood of receiving ART increased as initial CD4 lymphocyte counts decreased. Fifteen per cent of TB-HIV patients died during anti-tuberculosis treatment. Patients already on ART prior to anti-tuberculosis treatment experienced the worst outcomes. Patients who initiated ART early during anti-tuberculosis treatment or in the timeframe recommended by the guidelines fared the best.. HIV care has been successfully and sustainably integrated into TB services in Benin. However, ensuring the access of co-infected patients to more favourable treatment outcomes still represents significant challenges.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Antitubercular Agents; Benin; Coinfection; Counseling; Delivery of Health Care, Integrated; Female; Health Services Accessibility; Health Services Needs and Demand; HIV Infections; Humans; Male; Middle Aged; Predictive Value of Tests; Program Development; Program Evaluation; Registries; Retrospective Studies; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora infection can be difficult because of its scarcity in developed countries, intracellular mode of life, small size of the parasite and its inability to take up routine microscopic stains. However, it is endemic in many countries in Asia, Africa, Central and South America. With the increase in travels to these areas, the number of cases is expected to increase. Moreover, it is found to be associated with numerous food-borne outbreaks.. We encountered a patient with human immunodeficiency virus presented with 6 months of diarrhoea. The initial investigation was unrevealing. The diagnosis of Cyclospora infection was finally made on the histological sample obtained by colonoscopy. Moreover, the initial therapy with ciprofloxacin was not effective, while trimethoprim/sulfamethoxazole resulted in final cure of the disease.. Travel and food histories are important for the suspicion of Cyclospora infection. Histological examination is more sensitive in making a diagnosis of Cyclospora infection of the gut than fecal microscopic examination. Trimethoprim/sulfamethoxazole is a more reliable therapy for Cyclospora infection in patients with human immunodeficiency virus.

Topics: Adult; Anti-Infective Agents; Ciprofloxacin; Colonoscopy; Cyclospora; Cyclosporiasis; Diarrhea; Feces; Female; HIV; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Blood Glucose; Burkitt Lymphoma; CD4 Lymphocyte Count; Chromatography, High Pressure Liquid; Dapsone; Diabetes Mellitus, Type 2; Drug Interactions; Folic Acid Antagonists; Glycated Hemoglobin; HIV Infections; Humans; Male; Middle Aged; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child, Preschool; Coinfection; Dihydropteroate Synthase; Drug Resistance, Fungal; Female; France; Fungal Proteins; HIV Infections; Humans; Infant; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiration, Artificial; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Chemoprevention; Community-Acquired Infections; Cough; Dyspnea; Fatal Outcome; HIV Infections; Humans; Lymphatic Diseases; Lymphoma, Non-Hodgkin; Male; Medication Adherence; Pancytopenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Sarcoma, Kaposi; Trimethoprim, Sulfamethoxazole Drug Combination

The study explored the perceptions, knowledge and attitudes of patients, health workers and traditional healers about the use of traditional medicine and Anti Retroviral Therapy (ART). The study explored the perceptions, knowledge and attitudes of patients, health workers and traditional healers about the use of traditional medicine and Anti Retroviral Therapy (ART), using an exploratory qualitative design in two provinces of South Africa: an urban township health facility in the Western Cape, and a rural district hospital in KwaZulu-Natal (KZN) with antennal HIV rate of 32% and 28%'respectively. In-depth interviews were conducted with 14 participants: six HIV patients on ART and using Traditional Medicine(TM), two doctors, two nurses and four traditional healers. Two focus group discussions -one at each site - were held with community health workers who work with HIV-positive patients (Western Cape [5] and in KZN [4]). Patient said to have used Traditional Healing Practices (THP) before they were diagnosed with HIV, and some who have been diagnosed with HIV continue using TM in conjunction with ART and/or Cotrimoxazole prophylaxis. Patients preferred not to disclose THP to health professionals because of lack of support and understanding. Patients utilize THP because of family expectations, privacy and confidentiality, especially when they have not disclosed their HIV status. Healthcare professionals had strong negative opinions about THP, especially for HIV-positive patients. Traditional healers supported the patient's rationale for THP use. This study revealed a need to better understand factors involved in patients' choosing to use THP concurrently with ART.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Attitude of Health Personnel; Attitude to Health; Confidentiality; Disclosure; Family; Female; HIV; HIV Infections; Humans; Interviews as Topic; Male; Medicine, African Traditional; Patient Acceptance of Health Care; Perception; Physician-Patient Relations; Phytotherapy; Privacy; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

In sub-Saharan Africa, high mortality rates have been reported among patients with advanced HIV infection initiating antiretroviral therapy (ART). We evaluated the cost-effectiveness of expanding access to cotrimoxazole (CTX) for persons with HIV in averting mortality during the first 6 months of ART. We also evaluated possible cost savings related to prevention of specific opportunistic infections (OIs).. We developed a decision-analytic model to estimate the incremental cost, deaths averted, and incremental cost-effectiveness ratio. The model compared 2 scenarios for providing CTX and evaluated potential benefits of increased CTX coverage in reducing deaths and cases of OI. The base case scenario represents an estimated current level of CTX coverage among adults initiating ART in low-income countries (65%). The comparator is 97% coverage (excluding only those with contraindications to CTX). We conducted sensitivity analyses on all parameters in the model.. Full coverage reduced deaths from 94 to 72 per 1000 patients, averting 22 deaths during the first 6 months of ART compared with the base case. The incremental cost of moving from base case to full coverage was estimated at $3.29 per person on ART and $146.91 per death averted over 6 months. Additional benefits from averted OI cases would likely be realized as well as savings from averted OI treatment costs.. Our findings suggest that expanding CTX coverage is a cost-effective approach to reducing mortality among patients who present with advanced HIV and initiate ART. The expansion of coverage may also yield benefits for OIs.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Cost-Benefit Analysis; HIV Infections; Humans; Models, Statistical; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Soft Tissue Infections; Staphylococcal Skin Infections; Trimethoprim, Sulfamethoxazole Drug Combination

To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade.. Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010.. The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010.. The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).

Topics: Adolescent; Adult; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Cooperative Behavior; Female; Follow-Up Studies; Government Programs; Health Promotion; HIV Infections; Humans; Male; Middle Aged; Pregnancy; Prevalence; Program Evaluation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult; Zambia

HIV infections are a growing concern in the elderly as a result of improvements in therapeutics and monitoring, which have extended the life span for this HIV-infected population. Elderly patients potentially are more complicated to treat than younger HIV-infected individuals because of comorbidities and the physiological effects of aging on pharmacokinetics and pharmacodynamics. The patient, a 67-year-old African-American HIV-infected male, presents to the transitional care unit of university-affiliated hospital refusing to take medications and undergo laboratory testing, including blood draws. This patient's treatment is further complicated by poor renal function, medications with potential interactions, and a recent diagnosis of depression. This case demonstrates treatment and monitoring of an elderly patient with HIV and reveals the complications associated with this disease state. Specifically, it identifies nonadherence to medications and a lack of laboratory results, which affect the efficacy of treatment and monitoring, medication adjustments based on metabolism and renal excretion, monitoring of adverse effects of HIV and antiretroviral therapy, and comorbid conditions that may be linked to HIV and antiretroviral therapy such as depression and bone disease. Education on HIV medications, monitoring, and standards of care for pharmacists working with the geriatric population is warranted and should be emphasized as the HIV-infected elderly population continues to grow.

Topics: Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antihypertensive Agents; Azithromycin; CD4 Lymphocyte Count; Depressive Disorder; Diltiazem; Drug Interactions; Drug Monitoring; HIV Infections; Humans; Hypertension; Lopinavir; Male; Patient Compliance; Pharmacists; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

A recent study reported that trimethoprim/sulfamethoxazole caused acute psychosis in four renal transplant patients with Pneumocystis jirovecii pneumonia. We aimed to investigate the incidence of and factors associated with trimethoprim/sulfamethoxazole-related acute psychosis in HIV-infected patients with P. jirovecii pneumonia.. We reviewed the medical records of HIV-infected patients who presented with P. jirovecii pneumonia and received trimethoprim/sulfamethoxazole at six major hospitals in Taiwan from July 2009 to May 2011. Acute psychosis was defined as the occurrence of hallucinations or delusions following the initiation of trimethoprim/sulfamethoxazole during hospitalization.. During the study period, 135 patients receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia were enrolled and 16 (11.9%; 95% CI, 6.3%-17.4%) developed acute psychosis after a median duration of 5 days of trimethoprim/sulfamethoxazole treatment (range, 3-11 days). The incidence increased from 0% (0/16) in patients who received a daily trimethoprim dose of ≤12 mg/kg to 23.5% (4/17) in those who received a daily trimethoprim dose of >18 mg/kg. In multivariate logistic regression analysis, a higher daily dose of trimethoprim/sulfamethoxazole (OR, per 1 mg increase of trimethoprim, 1.40; 95% CI, 1.12-1.76; P = 0.0035) and use of adjunctive steroids (OR, 4.43; 95% CI, 1.14-17.15; P = 0.031) were associated with acute psychosis.. In this case series, 11.9% of HIV-infected patients developed acute psychosis while receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia. While the study was limited by its retrospective design, the risk appeared to increase with increasing daily dose of trimethoprim/sulfamethoxazole in those vulnerable patients with multiple risks for acute psychosis.

Topics: Adult; Aged; Anti-Infective Agents; Female; HIV Infections; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Psychotic Disorders; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity.. Seventy seven single nucleotide polymorphisms (SNPs) from 14 candidate genes were genotyped and assessed for association with SMX-induced hypersensitivity, in a cohort of 171 HIV/AIDS patients. SNP rs761142 T > G, in glutamate cysteine ligase catalytic subunit (GCLC), was significantly associated with SMX-induced hypersensitivity, with an adjusted p value of 0.045. This result was replicated in a second cohort of 249 patients (p = 0.025). In the combined cohort, heterozygous and homozygous carriers of the minor G allele were at increased risk of developing hypersensitivity (GT vs TT, odds ratio = 2.2, 95% CL 1.4-3.7, p = 0.0014; GG vs TT, odds ratio = 3.3, 95% CL 1.6 - 6.8, p = 0.0010). Each minor allele copy increased risk of developing hypersensitivity 1.9 fold (95% CL 1.4 - 2.6, p = 0.00012). Moreover, in 91 human livers and 84 B-lymphocytes samples, SNP rs761142 homozygous G allele carriers expressed significantly less GCLC mRNA than homozygous TT carriers (p < 0.05).. rs761142 in GCLC was found to be associated with reduced GCLC mRNA expression and with SMX-induced hypersensitivity in HIV/AIDS patients. Catalyzing a critical step in glutathione biosynthesis, GCLC may play a broad role in idiosyncratic drug reactions.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Catalytic Domain; Female; Genotyping Techniques; Glutamate-Cysteine Ligase; Glutathione; HIV Infections; Humans; Hypersensitivity; Inactivation, Metabolic; Male; Polymorphism, Single Nucleotide; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

The authors had for aim to assess the management of tuberculosis and HIV co-infection in Cotonou, Benin.. We made a cross-sectional, retrospective, and descriptive study comparing the clinical presentation and outcome of patients with tuberculosis and HIV co-infection versus patients with tuberculosis alone, all managed at the National Pneumophtisiology Center in Cotonou, Benin, in 2009.. The rate of HIV screening in TB patients was 99%. One thousand and eighty-six TB patients were included and 259 were HIV positive. The mean age of co-infected patients was 36 years, versus 34 for TB mono-infected patients. The sex ratio among co-infected was 1.15 versus 2.25 among TB patients. Positive pulmonary sputum was less frequent with co-infection. Two hundred and fifty-seven over 259 patients were treated with cotrimoxazole. One hundred and eighty-five over 234 (79.05%) had CD4 counts<350. Eighty-five (46%) of the 185 patients with CD4<350, were given antiretroviral therapy. Treatment success rate was lower for co-infected (75%) than for patients with TB alone (86%), and death rates were higher in co-infected patients (10% vs. 3%).. High death rate and high rate of lost to follow-up are arguments for systematic antiretroviral treatment of co-infected patients. Early screening for TB and HIV, and reviewing the current national recommendations, as well as an increased governmental effort to provide medicines to all patients in need of ARV are mandatory.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Benin; CD4 Lymphocyte Count; Comorbidity; Cross-Sectional Studies; Disease Management; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Mass Screening; Middle Aged; Mycobacterium tuberculosis; Prevalence; Retrospective Studies; Sputum; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia.. From 2005 to 2009, we conducted a cross-sectional study of HIV-infected pregnant women at Thyolo Hospital, Malawi. Blood was tested for malaria parasitemia and anemia (hemoglobin<11 g/dl). Data were collected on use of anti-malaria interventions and other risk factors. CTX prophylaxis policy for HIV-infected pregnant women was introduced in 2007, but implementation problems resulted in some women receiving both CTX and SP-IPTp.. We enrolled 1,142 women, of whom 1,121 had data on CTX and/or SP-IPTp intake. Of these, 49.7%, 29.8%, and 15.4% reported taking SP-IPTp only, CTX only and SP-IPTp plus CTX, respectively. Compared with women taking SP-IPTp, those taking SP-IPTp plus CTX and CTX were less likely to have malaria parasitemia (OR, [95%CI]: 0.09, [0.01-0.66] and 0.43, [0.19-0.97], respectively) or anemia (PR, [95% CI]: 0.67, [0.54-0.83] and 0.72, [0.61-0.83], respectively).. In HIV-infected pregnant women, daily CTX was associated with reduced malaria parasitemia and anemia compared with SP-IPTp. CTX plus SP-IPTp was associated with further reduction in malaria parasitemia but toxicity was not fully assessed.

Topics: Adolescent; Adult; Anemia; Antimalarials; Chemoprevention; Cross-Sectional Studies; Drug Combinations; Female; HIV Infections; Humans; Malaria; Malawi; Middle Aged; Parasitemia; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Pyrimethamine; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting.. A cohort of HIV-1-infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6-monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 °C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random-effects Poisson regression for the effect of HAART at the population level.. A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person-years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrollment (CD4+ T-cell counts and WHO stage) and time since enrollment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART.. HAART availability in a resource-poor setting substantially reduced the trends of bacteraemia among HIV-infected adults. This may further impact on future morbidity and healthcare costs of HIV-infected people.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Bacteremia; CD4 Lymphocyte Count; Epidemiologic Methods; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).. Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.. Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.. In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.

Topics: Adult; Anti-HIV Agents; Antigens, Protozoan; Antimalarials; Antiretroviral Therapy, Highly Active; Chemoprevention; Cohort Studies; Cross-Sectional Studies; Female; HIV Infections; Humans; Malaria; Male; Plasmodium falciparum; Prevalence; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Urban Population

In the April 2010 issue of this journal, Date et al. expressed concern over the slow scale-up in low-income settings of two therapies for the prevention of opportunistic infections in people living with the human immunodeficiency virus: co-trimoxazole prophylaxis and isoniazid preventive therapy. This short paper discusses the important ways in which policy analysis can be of use in understanding and explaining how and why certain evidence makes its way into policy and practice and what local factors influence this process. Key lessons about policy development are drawn from the research evidence on co-trimoxazole prophylaxis, as such lessons may prove helpful to those who seek to influence the development of national policy on isoniazid preventive therapy and other treatments. Researchers are encouraged to disseminate their findings in a manner that is clear, but they must also pay attention to how structural, institutional and political factors shape policy development and implementation. Doing so will help them to understand and address the concerns raised by Date et al. and other experts. Mainstreaming policy analysis approaches that explain how local factors shape the uptake of research evidence can provide an additional tool for researchers who feel frustrated because their research findings have not made their way into policy and practice.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Developing Countries; Evidence-Based Medicine; Health Resources; HIV Infections; Humans; Malawi; Poverty; Primary Prevention; Socioeconomic Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Uganda; Zambia

To determine whether implementation of free cotrimoxazole (CTX) provision was associated with improved retention among clients ineligible for antiretroviral therapy (ART) enrolled in an HIV treatment program in Kenya.. Data were obtained from a clinical cohort for program evaluation purposes. Twelve-month clinic retention was compared among ART-ineligible clients enrolled in the time period before free CTX versus the time period after.. Statistical comparisons were made using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazards models. To exclude potential temporal program changes that may have influenced retention, ART clients before and after the same cut-off date were compared.. Among adult clients enrolled between 2005 and 2007, 3234 began ART within 1 year of enrollment, and 1024 of those who did not start treatment were defined as ART-ineligible. ART-ineligible clients enrolled in the period following free CTX provision had higher 12-month retention (84%) than those who enrolled prior to free CTX (63%; P < 0.001). Retention did not change significantly during these periods among ART clients (P = 0.55). In multivariate analysis, ART-ineligible clients enrolled prior to free CTX were more than twice as likely to be lost to follow-up compared to those following free CTX [adjusted hazard ratio (aHR) = 2.64, 95% confidence interval 1.95-3.57, P < 0.001].. Provision of free CTX was associated with significantly improved retention among ART-ineligible clients. Retention and CD4-monitoring of ART-ineligible clients are essential to promptly identify ART eligibility and provide treatment. Implementation of free CTX may improve retention in sub-Saharan Africa and, via increasing timely ART initiation, provide survival benefit.

Topics: Adult; Ambulatory Care Facilities; Anti-Infective Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Drug Costs; Female; HIV Infections; Humans; Kaplan-Meier Estimate; Kenya; Male; Patient Compliance; Program Evaluation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of rhabdomyolysis associated with trimethoprim-sulphamethoxazole (TMP-SMZ) in a HIV-infected patient. A 33-year-old African American man with newly diagnosed AIDS initially presented with persistent, high-grade fevers suspected to be TMP-SMZ-related drug fever. The antibiotic was discontinued while in the hospital, but the patient was restarted on TMP-SMZ following discharge. Two days later, he returned to the hospital with severe muscle pain, acute renal failure and a significantly elevated creatine phosphokinase consistent with rhabdomyolysis. The patient gradually improved following discontinuation of TMP-SMZ.

Topics: Adult; Anti-Bacterial Agents; HIV Infections; Humans; Male; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

WHO guidelines recommend cotrimoxazole prophylaxis (CTXP) in all HIV-exposed negative infants who are still breastfeeding. This is based on the evidence of efficacy in HIV-infected infants, but there is no evidence of benefit in HIV-negative, breast-fed infants. We assessed the impact of CTXP on diarrhoeal and respiratory morbidity in breast-fed, HIV-exposed negative infants in a community programme. CTXP for more than 60 days showed no consistent evidence of benefit for incidence of lower respiratory tract infection [incidence rate ratio (IRR) 0.71, 95% confidence interval (CI) 0.39-1.26; P = 0.241] but an increased incidence of diarrhoea (IRR = 1.38, 95% CI 0.98-1.94; P = 0.065). The guidelines should be reconsidered by conducting a randomized control trial.

Topics: Breast Feeding; Female; HIV Infections; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Male; Odds Ratio; Pregnancy; Risk Factors; Rural Population; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions.. District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART.. Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not.

Topics: Anti-Infective Agents; Anti-Retroviral Agents; Comorbidity; HIV Infections; Humans; Malawi; Outcome Assessment, Health Care; Primary Prevention; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

The purpose of this report is to describe four cases of nocardiosis observed over an eight-year period in medical units of Principal Hospital in Dakar, Senegal. It is a rare infection occurring mainly in people with weakened immune systems. Pulmonary forms are predominate and clinical and laboratory presentation can mimic pulmonary tuberculosis. Diagnosis should be suspected in patients presenting pulmonary infections and negative sputum bacilloscopy. Nocardia bacteria should be identified before starting antibiotic treatment. Patients require long-term antibiotic treatment with third generation cephalosporins or sulfamethoxazole-trimethoprim.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Diagnosis, Differential; Female; HIV Infections; HIV-1; Humans; Immunocompromised Host; Male; Middle Aged; Nocardia Infections; Radiography, Thoracic; Senegal; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Choroiditis; Female; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The association of paracoccidioidomycosis with AIDS is apparently less frequent than expected. The authors present an unusual case of paracoccidioidomycosis in a 13-year-old female student which was later found to be the first opportunistic infection in the course of the patient's HIV-infection. The clinical presentation followed an accidental incised wound on the palmar region initially described as a 'sporotrichotic-chancre'. After good response under sulfamethoxazole-trimethoprin, the patient relapsed and presented an associated oral candidiasis. HIV-infection was documented and additional investigation showed CD4(+) T-cells=22/mm(3), CD8(+)=280 cell/mm(3) and viral load=4,043 log. This case report presents an uncommon dermatological-clinical picture in the youngest patient in which such association has been reported to date.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Candidiasis, Oral; CD4 Lymphocyte Count; Female; Hand Injuries; HIV Infections; Humans; Paracoccidioidomycosis; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Highly active antiretroviral therapy (HAART) drastically reduces mother-to-child transmission of HIV, but where breastfeeding is the only safe infant feeding option, HAART for the prevention of mother-to-child transmission needs to be evaluated in relation to both HIV transmission and infant mortality.. One hundred and two > or = 18-year old women on HAART in rural Uganda who delivered one or more live infants between March 1, 2003 and January 1, 2007 were enrolled in a prospective study to assess HIV transmission and infant survival. All pregnant women were counseled to exclusively breastfeed for 3-6 months according to national guidelines at the time. Infants were followed-up for > or = 7 months and were offered HIV polymerase chain reaction testing quarterly from 6 weeks of age until > or = 6 weeks after complete weaning.. Of 118 infants born during follow-up, 109 (92%) were breastfed. Median durations of exclusive and total breastfeeding were 4 months (interquartile range 3-6) and 5 months (interquartile range 3-7), respectively. None of the infants tested HIV polymerase chain reaction positive over follow-up but 16 infants died without a definitive HIV status at a median age of 2.6 months. In total, 23 (19%) infants died during follow-up at a median age of 3.7 months; 15 (65%) of whom with severe diarrhea and/or vomiting in the week preceding their death. In multivariate analysis, there was a 6-fold greater risk of death among infants breastfed for less than 6 months independent of maternal CD4 count closest to delivery, maternal marital status or maternal death (adjusted hazard ratio = 6.19; 95% confidence interval 1.41-27.0, P = 0.015).. In resource-constrained settings, HIV-infected pregnant women should be assessed for HAART eligibility and treated as needed without delay, and should be encouraged to breastfeed their infants for at least 6 months.

Topics: Adolescent; Adult; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Breast Feeding; CD4 Lymphocyte Count; Developing Countries; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant Mortality; Infectious Disease Transmission, Vertical; Middle Aged; Mothers; Multivariate Analysis; Prospective Studies; Randomized Controlled Trials as Topic; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Bacterial pneumonia is still a substantial cause of morbidity and mortality in HIV-infected patients in the era of combination Antiretroviral Therapy. The benefit of tobacco withdrawal on the risk of bacterial pneumonia has not been quantified in such populations, exposed to other important risk factors such as HIV-related immunodeficiency. Our objective was to estimate the effect of tobacco smoking withdrawal on the risk of bacterial pneumonia among HIV-infected individuals.. Patients of the ANRS CO3 Aquitaine Cohort with >or= two visits during 2000-2007 and without bacterial pneumonia at the first visit were included. Former smokers were patients who stopped smoking since >or= one year. We used Cox proportional hazards models adjusted on CD4+ lymphocytes (CD4), gender, age, HIV transmission category, antiretroviral therapy, cotrimoxazole prophylaxis, statin treatment, viral load and previous AIDS diagnosis. 135 cases of bacterial pneumonia were reported in 3336 patients, yielding an incidence of 12 per thousand patient-years. The adjusted hazard of bacterial pneumonia was lower in former smokers (Hazard Ratio (HR): 0.48; P = 0.02) and never smokers (HR: 0.50; P = 0.01) compared to current smokers. It was higher in patients with <200 CD4 cells/microL and in those with 200 to 349 CD4 cells/microL (HR: 2.98 and 1.98, respectively; both P<0.01), but not in those with 350 to 499 CD4 cells/microL (HR: 0.93; P = 0.79), compared to those with >or=500 CD4 cells/microL. The interaction between CD4 cell count and tobacco smoking status was not statistically significant.. Smoking cessation dramatically reduces the risk of bacterial pneumonia, whatever the level of immunodeficiency. Smoking cessation interventions should become a key element of the clinical management of HIV-infected individuals.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Cohort Studies; Female; HIV Infections; Humans; Male; Middle Aged; Nicotiana; Pneumonia, Bacterial; Proportional Hazards Models; Risk Factors; Smoking Cessation; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a major source of morbidity and mortality globally. The World Health Organization (WHO) has recommended that HIV counselling and testing be offered routinely to TB patients in order to increase access to HIV care packages. We assessed the uptake of provider-initiated testing and counselling (PITC), antiretroviral (ART) and co-trimoxazole preventive therapies (CPT) among TB patients in the Northwest Region, Cameroon.. A retrospective cohort study using TB registers in 4 TB/HIV treatment centres (1 public and 3 faith-based) for patients diagnosed with TB between January 2006 and December 2007 to identify predictors of the outcomes; HIV testing/serostatus, ART and CPT enrollment and factors that influenced their enrollment between public and faith-based hospitals.. A total of 2270 TB patients were registered and offered pre-HIV test counselling; 2150 (94.7%) accepted the offer of a test. The rate of acceptance was significantly higher among patients in the public hospital compared to those in the faith-based hospitals (crude OR 1.97; 95% CI 1.33 - 2.92) and (adjusted OR 1.92; 95% CI 1.24 - 2.97). HIV prevalence was 68.5% (1473/2150). Independent predictors of HIV-seropositivity emerged as: females, age groups 15-29, 30-44 and 45-59 years, rural residence, previously treated TB and smear-negative pulmonary TB. ART uptake was 50.3% (614/1220) with 17.2% (253/1473) of missing records. Independent predictors of ART uptake were: previously treated TB and extra pulmonary TB. Finally, CPT uptake was 47.0% (524/1114) with 24% (590/1114) of missing records. Independent predictors of CPT uptake were: faith-based hospitals and female sex.. PITC services are apparently well integrated into the TB programme as demonstrated by the high testing rate. The main challenges include improving access to ART and CPT among TB patients and proper reporting and monitoring of programme activities.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Retroviral Agents; Cameroon; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Female; Health Services Accessibility; HIV Infections; HIV Seroprevalence; Humans; Infant; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Topics: Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Bacterial Infections; CD4 Lymphocyte Count; Drug Therapy, Combination; HIV Infections; Humans; Malaria; Mycoses; Protozoan Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults.. Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per muL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779.. 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0.65, 95% CI 0.50-0.85; p=0.001). Mortality risk reduction on ART was substantial to 12 weeks (0.41, 0.27-0.65), sustained from 12-72 weeks (0.56, 0.37-0.86), but not evident subsequently (0.96, 0.63-1.45; heterogeneity p=0.02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0.74, 0.63-0.88; p=0.0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0.86, 0.69-1.07; p=0.17), CD4 cell count (difference vs non-users, -3 cells per muL [-12 to 6]; p=0.50), or BMI (difference vs non-users, -0.04 kg/m(2) [-0.20 to 0.13); p=0.68].. Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa.. UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; HIV Infections; Humans; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Zimbabwe

In July 2005, Médecins Sans Frontières and the Ministry of Health, Kenya, implemented an integrated tuberculosis-human immunodeficiency virus (TB-HIV) programme in western Kenya.. To evaluate the impact of an integrated TB-HIV programme on patient care and TB programme outcomes.. Retrospective evaluation of three time periods: before (January-June 2005), shortly after (January-June 2006) and medium term after (January-December 2007) the implementation of the integrated programme.. Respectively 79% and 91% of TB patients were HIV tested shortly and at medium term after service integration. The HIV-positive rate varied from 96% before the intervention to respectively 88% (305/347) and 74% (301/405) after. The estimated number of HIV-positive cases was respectively 303, 323 and 331 in the three periods. The proportion of patients receiving cotrimoxazole prophylaxis increased significantly from 47% (142/303) to 94% (303/323) and 86% (285/331, P < 0.05). Before the intervention, 87% (171/197) of the TB-HIV patients would have been missed when initiating antiretroviral treatment, compared to respectively 29% (60/210) and 36% (78/215) after the integration. The TB programme success rate increased from 56% (230/409) to 71% (319/447) in the third period (P < 0.05); however, there was no significant decrease in the default rate: 20% to 22% (P = 0.66) and 18% (P = 0.37).. Integrated TB-HIV care has a very positive impact on the management of TB-HIV patients and on TB treatment outcomes.

Topics: Anti-HIV Agents; Anti-Infective Agents; Delivery of Health Care, Integrated; HIV Infections; Humans; Kenya; Patient Care; Retrospective Studies; Rural Health Services; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

To measure progress in implementing co-trimoxazole prophylaxis (CTXp) (trimethoprim plus sulfamethoxazole) and isoniazid preventive therapy (IPT) policy recommendations, identify barriers to the development of national policies and pinpoint challenges to implementation.. In 2007 we conducted by e-mail a cross-sectional survey of World Health Organization (WHO) HIV/AIDS programme officers in 69 selected countries having a high burden of infection with HIV or HIV-associated tuberculosis (TB). The specially-designed, self-administered questionnaire contained items covering national policies for CTXp and IPT in people living with HIV, current level of implementation and barriers to developing or implementing these policies.. The 41 (59%) respondent countries, representing all WHO regions, comprised 85% of the global burden of HIV-associated TB and 82% of the global burden of HIV infection. Thirty-eight countries (93%) had an established national policy for CTXp, but only 66% of them (25/38) had achieved nationwide implementation. For IPT, 21 of 41 countries (51%) had a national policy but only 28% of them (6/21) had achieved nationwide implementation. Despite significant progress in the development of CTXp policy, the limited availability of co-trimoxazole for this indication and inadequate systems to manage drug supply impeded nationwide implementation. Inadequate intensified tuberculosis case-finding and concerns regarding isoniazid resistance were challenges to the development and implementation of national IPT policies.. Despite progress in implementing WHO-recommended CTXp and IPT policies, these interventions remain underused. Urgent steps are required to facilitate the development and implementation of these policies.

Topics: Anti-Infective Agents; Antitubercular Agents; Cross-Sectional Studies; HIV Infections; HIV Long-Term Survivors; Humans; Isoniazid; Practice Patterns, Physicians'; Public Policy; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

A prospective cohort design was used to measure the association between daily cotrimoxazole-prophylaxis and infection with Plasmodium falciparum containing mutations associated with antifolate resistance among persons infected with human immunodeficiency virus (HIV) in Tororo and Busia District, in eastern Uganda. Of 149 cases of P. falciparum parasitemia diagnosed, 147 (99%) (smears from participants taking prophylaxis = 91 and smears from those not taking cotrimoxazole prophylaxis = 56) were successfully assessed for mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations associated with antifolate resistance. Prevalences of the dhfr pure triple mutant (74% and 70%; P = 0.71), the dhps pure double mutant (95% and 88%; P = 0.21), and the dhfr/dhps pure quintuple mutant (73% and 64%; P = 0.36), were not significantly different between those taking and those not taking cotrimoxazole-prophylaxis, respectively. The overall prevalence of the pure quintuple mutant in this study was 69%, which is among the highest in Africa. Although resistance rates of P. falciparum to antifolate drugs are high, cotrimoxazole-prophylaxis in HIV-infected persons was not associated with a higher prevalence of mutations associated with antifolate resistance.

Topics: Adolescent; Adult; Animals; Antimalarials; Child; Child, Preschool; Cohort Studies; Dihydropteroate Synthase; Drug Resistance; Female; Folic Acid; Folic Acid Antagonists; HIV Infections; Humans; Malaria, Falciparum; Male; Mutation; Plasmodium falciparum; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Food insecurity is considered to be an important contributor to HIV associated wasting in sub-Saharan Africa. Low body mass index (BMI) is a strong risk factor for early mortality during antiretroviral therapy (ART). Nutritional supplementation has become standard of care in wasted patients starting ART in many countries in the region, but there is no unequivocal evidence base for this intervention. Against this background, we performed a retrospective study to compare food supplementation versus no nutritional intervention in wasted adults starting ART in Blantyre, Malawi. All patients received free nevirapine, lamivudine, and stavudine. Participants in an effectiveness trial of two food supplements received either corn-soy blend (CSB) or ready-to-use food spread (RUFS) during the first 14 weeks of ART. Results were compared with a historical control group receiving no food supplement that was part of an observational cohort study of outcomes of the same ART regimen. Characteristics on initiation of ART were similar in the three groups, except the use of cotrimoxazole prophylaxis which was more frequent in the food-supplemented groups. Linear regression analysis showed that increase in BMI was greatest in the RUFS group and better in the CSB group than in those receiving no food supplementation at 14 weeks. These differences were no longer significant at 26 weeks. Lower BMI, CD4 count and hemoglobin, WHO clinical stage IV, male gender, and not receiving cotrimoxazole prophylaxis were independent risk factors for mortality at 14 and 26 weeks in the logistic regression analysis. Supplementary food use was not directly associated with improved survival.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Anti-Retroviral Agents; Body Mass Index; CD4 Lymphocyte Count; Cohort Studies; Dietary Supplements; Drug Therapy, Combination; Female; HIV Infections; HIV Wasting Syndrome; Humans; Lamivudine; Linear Models; Malawi; Male; Middle Aged; Nevirapine; Retrospective Studies; Risk Factors; Soy Foods; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zea mays

Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS.. Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance.. Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children.. Despite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation.

Topics: Antimalarials; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Folic Acid Antagonists; Follow-Up Studies; HIV Infections; Humans; Incidence; Infant; Insecticide-Treated Bednets; Malaria, Falciparum; Male; Mutation; Plasmodium falciparum; Polymerase Chain Reaction; Polymorphism, Genetic; Prevalence; Risk Factors; Tetrahydrofolate Dehydrogenase; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Dihydropteroate Synthase; Genotype; HIV Infections; HIV-1; Hospital Mortality; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Spain; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Improved documentation of human immunodeficiency virus (HIV) testing and care among tuberculosis (TB) patients is needed to strengthen TB-HIV programs. In 2007, Kenya piloted the use of personal digital assistants (PDAs) instead of paper registers to collect TB-HIV surveillance data from TB clinics.. To evaluate the acceptability, data quality and usefulness of PDAs.. We interviewed four of 31 district coordinators who collected data in PDAs for patients initiating TB treatment from April to June 2007. In 10 of 93 clinics, we randomly selected patient records for comparison with corresponding records in paper registers or PDAs. Using Cochran-Mantel-Haenszel tests, we compared missing data proportions in paper registers with PDAs. We evaluated PDA usefulness by analyzing PDA data from all 93 clinics.. PDAs were well accepted. Patient records were more frequently missing (28/97 vs. 1/112, P < 0.001) and data fields more frequently incomplete (148/1449 vs. 167/2331, P = 0.03) in PDAs compared with paper registers. PDAs, however, facilitated clinic-level analyses: 48/93 (52%) clinics were not reaching the targets of testing >or=80% of TB patients for HIV, and 8 (9%) clinics were providing <80% of TB-HIV co-infected patients with cotrimoxazole (CTX).. PDAs had high rates of missing data but helped identify clinics that were undertesting for HIV or underprescribing CTX.

Topics: Ambulatory Care Facilities; Anti-Infective Agents; Computers, Handheld; HIV Infections; Humans; Kenya; Pilot Projects; Population Surveillance; Practice Patterns, Physicians'; Registries; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Adverse drug reactions occur at a greater frequency in HIV-infected individuals. A 38-year-old Eritrean man was treated with outpatient co-trimoxazole for confirmed Pneumocystis jirovecii pneumonia, but was switched to clindamycin and primaquine due to nausea and vomiting. Following development of methaemaglobinaemia, he was recommenced on prophylactic co-trimoxazole. He was later found moribund with features resembling septic shock and required invasive respiratory support. The diagnosis of a rare, but severe reaction to co-trimoxazole did not become apparent until he was rechallenged with prophylactic co-trimoxazole after recovery from his initial severe reaction. In an era of polypharmacy and an increasing availability of novel drugs, this case is a timely reminder to clinicians of the ongoing need for pharmacovigilance, especially in HIV-infected individuals who may have unusual presentations of an adverse drug reaction.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Shock, Septic; Trimethoprim, Sulfamethoxazole Drug Combination

More than 80% of the people infected with HIV in low-income countries of sub-Saharan Africa do not know their HIV serostatus. Innovative measures of increasing access to HIV counseling and testing (HCT) are urgently needed so as to improve care and prevention. We implemented a home-based HCT program in Bushenyi District from September 2004 to March 2007, in Uganda where approximately 90% of people aged older than 14 years had never tested for HIV to gauge whether it was acceptable and increased uptake of HCT. Twenty-nine teams comprising a counselor and a laboratory assistant systematically visited homes offering HCT for all people older than 14 years of age and at-risk children (mother deceased or HIV infected) using a rapid HIV testing three-test algorithm. HIV-infected people received cotrimoxazole prophylaxis, were supplied with long-lasting insecticide-treated bed nets and equipment for treatment of drinking water at home, and were referred for assessment for antiretroviral therapy. The program reached 92,984 (63%) of all the homes in the district. Of these, 32,3621 people were eligible for HCT, and 28,2857 (87%) were present at home and were offered pretest counseling. A total of 264,966 (94%) accepted testing and received their results, of whom 11,359 (4.3%) were HIV-infected. Ninety percent of those testing had never tested before. The cost of testing was $7.83 per previously untested client. Ninety-seven percent of HIV-infected people initiated cotrimoxazole prophylaxis, 74% received bed nets, 70% received water treatment equipment, and 11% began antiretroviral therapy. Forty-four percent of people who were in an HIV-discordant relationship were infected. These results demonstrate that home-based HCT was well-accepted, feasible, and effective in identifying HIV-infected individuals who did not know their HIV status in rural Uganda.

Topics: Adolescent; Adult; AIDS Serodiagnosis; Child; Child, Preschool; Cost-Benefit Analysis; Counseling; Female; HIV Infections; HIV Seropositivity; Home Care Services; Humans; Infant; Male; Middle Aged; Patient Acceptance of Health Care; Program Evaluation; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Cryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/µl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients.. A MARKOV DECISION TREE WAS USED TO COMPARE THE FOLLOWING STRATEGIES AT THE TIME OF HIV DIAGNOSIS: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/µl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US$ 2009) were from Cambodia. Efficacy data were from international literature.. In a population in which 81% of patients had a CD4+ count ≤50 cells/ µl and 19% a CD4+ count between 51-100 cells/µl, the proportion alive 1 year after enrollment was 61% (cost $ 472) with no intervention, 70% (cost $ 483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of follow-up, the cost-effectiveness of screening vs. no intervention was US$ 180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated at $1538/LYG if the proportion of patients with CD4+ count ≤50 cells/µl decreased by 75%.. In a high endemic area of cryptococcosis and HIV infection, serum CRAG screening and prophylaxis are two cost effective strategies to prevent AIDS associated cryptococcosis in patients with CD4+ count ≤100 cells/µl, at a short-term horizon, screening being more cost-effective but less effective than prophylaxis. Systematic primary prophylaxis may be preferred in patients with CD4+ below 50 cells/µl while systematic serum CRAG screening for early targeted treatment may be preferred in patients with CD4+ between 51-100 cells/µl.

Topics: AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antifungal Agents; Cambodia; CD4 Lymphocyte Count; Cost-Benefit Analysis; Cryptococcosis; Fluconazole; Follow-Up Studies; HIV Infections; Humans; Markov Chains; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In resource-limited settings, high case-fatality rates are seen among tuberculosis (TB) patients with human immunodeficiency virus (HIV) infection, especially during the early months of TB treatment. HIV prevalence among TB patients has been estimated to be as high as 80%--90% in some areas of sub-Saharan Africa. In 2004, the World Health Organization (WHO) recommended increasing collaboration between HIV and TB programs. Since then, many countries, including Kenya, have worked to increase TB/HIV collaborative activities. In 2005, the Kenya Division of Leprosy, Tuberculosis, and Lung Disease (DLTLD) added questions regarding HIV testing and treatment to the existing TB surveillance system.* This report summarizes HIV data collected from Kenya's extended TB surveillance system during 2006--2009. During this period, HIV testing among TB patients increased from 60% in 2006 to 88% in 2009, and the prevalence of HIV infection among TB patients tested decreased from 52% to 44%. In 2009, 92% of HIV-infected TB patients received cotrimoxazole prophylaxis for the prevention of opportunistic infections. Although these data highlight the increase in HIV services provided to TB patients, only 34% of HIV-infected TB patients started antiretroviral therapy (ART) while being treated for TB. Innovative interventions are needed to increase HIV treatment among TB patients in Kenya, especially considering the 2009 WHO guidelines recommending that all HIV-infected TB patients be started on ART as soon as possible, regardless of CD4 count. Although these guidelines have not yet been implemented in Kenya, officials are working to identify methods of increasing access to ART for TB patients.

Topics: CD4 Lymphocyte Count; Health Facilities; Health Policy; HIV Infections; Humans; Kenya; Mass Screening; Population Surveillance; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Topics: Anti-Infective Agents; Clinical Protocols; Developing Countries; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India.. Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons.. Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations..   Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Female; HIV Infections; Humans; India; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

New diagnoses of tuberculosis (TB) present important opportunities to detect and treat HIV. Rates of HIV and TB in Indonesia's easternmost Papua Province exceed national figures, but data on co-infection rates and outcomes are lacking. We aimed to measure TB-HIV co-infection rates, examine longitudinal trends, compare management with World Health Organisation (WHO) recommendations, and document progress and outcome.. Adults with newly-diagnosed smear-positive pulmonary TB managed at the Timika TB clinic, Papua Province, were offered voluntary counselling and testing for HIV in accordance with Indonesian National Guidelines, using a point-of-care antibody test. Positive tests were confirmed with 2 further rapid tests. Study participants were assessed using clinical, bacteriological, functional and radiological measures and followed up for 6 months.. Of 162 participants, HIV status was determined in 138 (85.2%), of whom 18 (13.0%) were HIV+. Indigenous Papuans were significantly more likely to be HIV+ than Non-Papuans (Odds Ratio [OR] 4.42, 95% confidence interval [CI] 1.38-14.23). HIV prevalence among people with TB was significantly higher than during a 2003-4 survey at the same TB clinic, and substantially higher than the Indonesian national estimate of 3%. Compared with HIV- study participants, those with TB-HIV co-infection had significantly lower exercise tolerance (median difference in 6-minute walk test: 25 m, p = 0.04), haemoglobin (mean difference: 1.3 g/dL, p = 0.002), and likelihood of cavitary disease (OR 0.35, 95% CI 0.12-1.01), and increased occurrence of pleural effusion (OR 3.60, 95% CI 1.70-7.58), higher rates of hospitalisation or death (OR 11.80, 95% CI 1.82-76.43), but no difference in the likelihood of successful 6-month treatment outcome. Adherence to WHO guidelines was limited by the absence of integration of TB and HIV services, specifically, with no on-site ART prescriber available. Only six people had CD4+ T-cell counts recorded, 11 were prescribed co-trimoxazole and 4 received ART before, during or after TB treatment, despite ART being indicated in 14 according to 2006 WHO guidelines.. TB-HIV co-infection in southern Papua, Indonesia, is a serious emerging problem especially among the Indigenous population, and has risen rapidly in the last 5 years. Major efforts are required to incorporate new WHO recommendations on TB-HIV management into national guidelines, and support their implementation in community settings.

Topics: Adult; Anti-Retroviral Agents; Antitubercular Agents; CD4 Lymphocyte Count; Coinfection; Female; HIV Infections; Humans; Indonesia; Male; Models, Biological; Prevalence; Prospective Studies; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Trimethoprim sulfamethoxazole (cotrimoxazole, CTX) is used frequently as part of standard medical care for people living with HIV/AIDS in Africa. The mechanisms of resistance to sulfonamides and trimethoprim in commensal streptococci from Uganda were determined and compared to S. pneumoniae. Commensal streptococci showing high-level resistance to cotrimoxazole were cultured and analysed for species identity and polymorphisms in the genes coding for dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Seven isolates of S. pneumoniae from blood and cerebrospinal fluid (CSF) were similarly examined. There was considerable polymorphism in both DHPS and DHFR. In DHFR, the mutations E20D and I100L were present in all sequenced isolates. Other mutations such as L135F, and different substitutions in D92, were frequent. The most common DHPS variants had 2 serine residues added after amino acid 60, or arginine and proline added after amino acid 59. In addition, 3 new insertions/substitutions were found. There were no obvious differences between the mutation patterns in S. pneumoniae and commensal streptococci, suggesting that the chromosomal mutations have been spread by transformational interchanges of DNA among related organisms.

Topics: Amino Acid Sequence; Anti-Infective Agents; Bacterial Proteins; Carrier State; Dihydropteroate Synthase; DNA Mutational Analysis; Drug Resistance, Bacterial; HIV Infections; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Streptococcus; Streptococcus pneumoniae; Superoxide Dismutase; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

We conducted a prospective, multicenter observational cohort study in Thailand to characterize the epidemiology of extrapulmonary tuberculosis (TB) in HIV-infected persons and to identify risk factors for death.. From May 2005 to September 2006, we enrolled, interviewed, examined, and performed laboratory tests on HIV-infected adult TB patients and followed them from TB treatment initiation until the end of TB treatment. We conducted multivariate proportional hazards analysis to identify factors associated with death.. Of the 769 patients, pulmonary TB only was diagnosed in 461 (60%), both pulmonary and extrapulmonary TB in 78 (10%), extrapulmonary TB at one site in 223 (29%), and extrapulmonary TB at more than one site in seven (1%) patients. Death during TB treatment occurred in 59 of 308 patients (19%) with any extrapulmonary involvement. In a proportional hazards model, patients with extrapulmonary TB had an increased risk of death if they had meningitis, and a CD4+ T-lymphocyte count <200 cells/microl. Patients who received co-trimoxazole, fluconazole, and antiretroviral therapy during TB treatment had a lower risk of death.. Among HIV-infected patients with TB, extrapulmonary disease occurred in 40% of the patients, particularly in those with advanced immune suppression. Death during TB treatment was common, but the risk of death was reduced in patients who took co-trimoxazole, fluconazole, and antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Cohort Studies; Female; Fluconazole; HIV Infections; Humans; Male; Risk Factors; Survival Analysis; Survival Rate; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Tuberculosis, Pulmonary; Young Adult

To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility.. Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients' characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel-Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole.. A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g/dl and median CD4+ 131 cells/microl) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g/dl and median CD4+ 130 cells/microl) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12-0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45-0.94).. These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.

Topics: Adult; Aged; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Topics: Anti-Infective Agents; Child; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; HIV Infections; Humans; Male; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The human immunodeficiency virus (HIV) pandemic is one of the most serious health crises facing the world. Of the estimated 33.2 million people living with HIV worldwide, 22.5 million (68%) live in Sub-Saharan Africa, where women of childbearing age are most severely affected. Children primarily acquire HIV infection through mother-to-child transmission. Despite recent encouraging success, low-income countries have not been able to effectively curtail transmission of HIV to the infant during or after pregnancy, resulting in about 90% of the estimated 420,000 newly infected children per annum occurring in Sub-Saharan Africa.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Breast Feeding; Developing Countries; Disease Progression; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Lamivudine; Maternal Mortality; Nevirapine; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization; Zidovudine

HIV-infected persons suffering from tuberculosis experience high mortality. No programmatic studies from India have documented the delivery of mortality-reducing interventions, such as cotrimoxazole prophylactic treatment (CPT) and antiretroviral treatment (ART). To guide TB-HIV policy in India we studied the effectiveness of delivering CPT and ART to HIV-infected persons treated for tuberculosis in three districts in Andhra Pradesh, India, and evaluated factors associated with death.. We retrospectively abstracted data for all HIV-infected tuberculosis patients diagnosed from March 2007 through August 2007 using standard treatment outcome definitions. 734 HIV-infected tuberculosis patients were identified; 493 (67%) were males and 569 (80%) were between the ages of 24-44 years. 710 (97%) initiated CPT, and 351 (50%) collected >60% of their monthly cotrimoxazole pouches provided throughout TB treatment. Access to ART was documented in 380 (51%) patients. Overall 130 (17%) patients died during TB treatment. Patients receiving ART were less likely to die (adjusted hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.3-0.6), while males and those with pulmonary TB were more likely to die (HR 1.7, 95% CI 1.1-2.7, and HR 1.9, 95% CI 1.1-3.2 respectively).. Among HIV-infected TB patients in India death was common despite the availability of free cotrimoxazole locally and ART from referral centres. Death was strongly associated with the absence of ART during TB treatment. To minimize death, programmes should promote high levels of ART uptake and closely monitor progress in implementation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Anti-Retroviral Agents; Child; Female; HIV Infections; Humans; India; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Nocardia species is an uncommon pathogen that affects both immunosuppressed and immunocompetent patients. The clinical and microbiologic spectrum of nocardiosis has changed recently due to the widespread use of cotrimoxazole prophylaxis, the emergence of new types of immunosuppressed patients, and the improved identification of isolates using molecular techniques. Nocardia asteroides was traditionally considered the predominant organism, and prophylaxis with cotrimoxazole was considered almost universally protective. We conducted the current study to determine the incidence of nocardiosis and its microbiologic and clinical characteristics in a general hospital over the last 12 years. We reviewed the clinical records of all patients in whom Nocardia species was isolated from clinical specimens between 1995 and 2006. Nocardia isolates were identified by standard procedures and by 5' end 16S rRNA gene polymerase chain reaction (PCR) and sequencing. Susceptibility to cotrimoxazole, minocycline, imipenem, linezolid, and amikacin was determined by the broth microdilution method following the guidelines of the Clinical and Laboratory Standards Institute.The incidence of Nocardia infections did not increase significantly during the study period (0.39/100,000 inhabitants in 1995-1998 and 0.55/100,000 inhabitants in 2003-2006). Nocardia was recovered from 43 patients. Six were considered to be colonized. The colonizing species were N. farcinica, N. nova, and N. asteroides. All colonized patients had severe underlying pulmonary conditions and were treated with antimicrobials (6 patients) or corticosteroids (4 patients). Invasive nocardiosis was diagnosed in 37 patients (86.5% were men, and their mean age was 55.8 +/- 17.3 yr). The most common underlying condition in our institution was human immunodeficiency virus (HIV) infection (10 patients; 27%), followed by chronic obstructive pulmonary disease (8 patients; 21.6%), autoimmune diseases (8 patients; 21.6%), solid organ transplantation (7 patients; 18.9%), and cancer (4 patients; 10.8%). The most important risk factor for nocardiosis was corticosteroid administration (23 patients; 62.2%). Nocardiosis affected the lungs in 26 cases (70.3%), the skin in 3 cases (8.1%), and the central nervous system in 2 cases (5.4%). It was disseminated in 5 cases (13.5%) and caused otomastoiditis in 1 (2.7%). The species identified were N. cyriacigeorgica (32.4%), N. farcinica (24.3%), N. otitidiscaviarum (10.8%), N. veterana (8.1%

Topics: Adult; Aged; Anti-Infective Agents; Autoimmune Diseases; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Neoplasms; Nocardia; Nocardia Infections; Organ Transplantation; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years.. To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials.. Cost-effectiveness analysis by using a computer simulation model of HIV disease.. Published data from randomized trials and observational cohorts in South Africa.. HIV-infected patients in South Africa.. 5-year and lifetime.. Modified societal.. No treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L.. Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness.. If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved.. Initiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%.. This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission.. Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended.. National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Cohort Studies; Computer Simulation; Cost-Benefit Analysis; Decision Trees; Disease Progression; Drug Administration Schedule; Health Care Costs; HIV Infections; Humans; Life Expectancy; Sensitivity and Specificity; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; HIV Infections; Humans; Male; Patch Tests; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the quality of clinical care provided to patients with HIV in Felege Hiwot Referral Hospital. APPROACH AND DESIGN: Normative evaluation based on Donabedian's structure-process-outcome model of health care quality. Cross-sectional. was employed to gather data in September 2007.. Felege Hiwot Referral Hospital is a government hospital in North West Ethiopia. The hospital is providing clinical care for patients infected with HIV free of patient charge since 2005.. The evaluation used 10 process and 5 outcome indicators of quality measured by reviewing 351 randomly selected patient records and interview with 368 patients. Resource inventory was conducted to assess the availability of trained staff, laboratory facilities and drugs required for provision of HIV care.. All resources recommended by the national antiretroviral therapy (ART) Implementation Guideline including trained staff, laboratory facilities and drugs were continuously available, except for a shortage of cotrimoxazole. Despite this, important components of care and treatment recommended by national treatment guidelines were not delivered for significant portion of patients. The study showed that only 45.9% of patients eligible for cotrimoxazole prophylactic therapy (CPT) and 76.8% of patients eligible for ART were actually taking CPT and ART, respectively. Compliance with national guidelines to monitor patients was also found to be a major problem.. Availability of resources alone does not ensure the quality of HIV care and treatment. The study results indicate a need for regular monitoring and improvement of processes and outcomes of care in the Ethiopian Health System.

Topics: Adolescent; Anti-HIV Agents; Antibiotic Prophylaxis; Child; Child, Preschool; Cross-Sectional Studies; Ethiopia; Female; Guideline Adherence; HIV Infections; Humans; Infant; Male; Outcome and Process Assessment, Health Care; Patient Satisfaction; Quality of Health Care; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zidovudine

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.

Topics: Adolescent; Adult; Age Factors; Anti-Infective Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Drug Resistance, Viral; Europe; Female; Hepatitis, Viral, Human; HIV Infections; HIV Long-Term Survivors; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Patient Education as Topic; Pneumonia, Pneumocystis; Pregnancy; Randomized Controlled Trials as Topic; RNA, Viral; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women.. This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP) in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR.. Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW). Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used.. Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a considerable impact on the burden of LBW in this population.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; Cross-Sectional Studies; Drug Combinations; Female; Folic Acid; HIV Infections; HIV-1; Humans; Infectious Disease Transmission, Vertical; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prevalence; Pyrimethamine; Risk Factors; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients is usually treated with trimethoprim (TMP)-sulfamethoxazole (SMX) 1920 mg 3 times daily (approximately equivalent to TMP 15 mg/kg/day-SMX 75 mg/kg/day) for 21 days. Pharmacokinetic data suggest that lower doses would be equally efficacious and might be associated with a lower incidence of adverse effects. We conducted a retrospective review of case notes for the first episode of laboratory-confirmed PCP in HIV-infected patients treated at Auckland City Hospital, from January 1991 through December 2007. Seventy-three of 84 (87%) patients were treated with TMP-SMX 960 mg 4 times daily or 3 times daily (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day). The overall mortality was 5/73 (7%). The mortality in patients with severe disease (transcutaneous oxygen saturation on admission < or =84%) was 3/16 (19%) and in patients admitted to the intensive care unit was 5/9 (56%). Fifteen of 73 (21%) patients required a change to an alternative treatment regimen because of adverse effects (rash in 10, rash plus fever in 3, neutropenia in 1, fever plus headache in 1). Treatment of PCP in adult HIV-infected patients with TMP-SMX 960 mg QID or TID appears to have comparable efficacy to treatment with higher doses and to be associated with a lower rate of treatment limiting adverse effects.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Infections; Humans; Logistic Models; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Costs and Cost Analysis; Encephalitis; HIV Infections; Humans; Safety; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Africa; Anti-Infective Agents; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Twelve large public hospitals geographically distributed in Thailand.. To assess the uptake of diagnostic human immunodeficiency virus (HIV) counselling and testing (DCT), HIV prevalence in tuberculosis (TB) patients and HIV services provided to newly diagnosed HIV-infected TB patients.. We provided DCT in TB clinics to newly registered TB patients. Post-test counselling was provided at TB clinics for non-HIV-infected patients and at HIV voluntary counselling and testing centres for HIV-infected patients. HIV-infected patients were referred for HIV-related care during TB treatment.. From July to October 2006, 8% of 1086 new TB patients were known to be HIV-infected at the time of TB diagnosis. Of 1000 patients with unknown HIV status, 93% were tested: HIV infection was diagnosed in 11%. Including patients with previously diagnosed HIV infection, 17% of all TB patients were HIV-infected. Of 99 newly diagnosed HIV patients, 36% received cotrimoxazole prophylaxis. Of 41 with CD4 < 200 cells/microl, 42% began antiretroviral treatment during TB treatment.. The acceptance of DCT was high, but the provision of HIV services was disappointingly low. Increased staff capacity building, stronger coordination with the acquired immune-deficiency syndrome programme and better field supervision are needed to achieve universal access to care for HIV-infected TB patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Counseling; Female; HIV Infections; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Patient Acceptance of Health Care; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

While the spectrum of opportunistic infections due to HIV infection has been widely discussed, there are very limited data available in south India on certain incident infections especially urinary tract infections (UTI) in HIV-infected subjects.. Bacterial aetiology of 350 symptomatic UTI in HIV-infected subjects and the drug resistance pattern of the Escherichia coli isolates tested between June 2005 and July 2007 at the YRG Centre for AIDS Research and Education, a tertiary HIV Referral Centre in Chennai has been described here.. E. coli was the most common etiological agent of UTI in HIV patients, followed by Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus spp. and Staphylococcus epidermidis. Twenty-nine E. coli isolates were multi-drug-resistant and 83.3% of the isolates were resistant to sulfamethoxazole-trimethoprim.. Urinary pathogens in HIV-infected patients demonstrate high antimicrobial resistance and with majority of therapy for UTIs being empiric, constant updates of the aetiological agents and their drug susceptibility pattern would largely be beneficial to clinicians in choosing the right drug.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents, Urinary; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; HIV Infections; Humans; India; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Resistance; HIV Infections; Humans; Public Health; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the effect of daily cotrimoxazole, essential for HIV care, on development of antifolate-resistant Plasmodium falciparum, naso-pharyngeal Streptococcus pneumoniae (pneumococcus), and commensal Escherichia coli. HIV-positive subjects with CD4 cell count < 350 cells/muL (lower-CD4; N = 692) received cotrimoxazole; HIV-positive with CD4 cell count > or = 350 cells/muL (higher-CD4; N = 336) and HIV-negative subjects (N = 132) received multivitamins. Specimens were collected at baseline, 2 weeks, monthly, and at sick visits during 6 months of follow-up to compare changes in resistance, with higher-CD4 as referent. P. falciparum parasitemia incidence density was 16 and 156/100 person-years in lower-CD4 and higher-CD4, respectively (adjusted rate ratio [ARR] = 0.11; 95% confidence interval [CI] = 0.06-0.15; P < 0.001) and 97/100 person-years in HIV-negative subjects (ARR = 0.62; 95% CI = 0.44-0.86; P = 005). Incidence density of triple and quintuple dihydrofolate-reductase/dihydropteroate-synthetase mutations was 90% reduced in lower-CD4 compared with referent. Overall, cotrimoxazole non-susceptibility was high among isolated pneumococcus (92%) and E. coli (76%) and increased significantly in lower-CD4 subjects by Week 2 (P < 0.005). Daily cotrimoxazole prevented malaria and reduced incidence of antifolate-resistant P. falciparum but contributed to increased pneumococcus and commensal Escherichia coli resistance.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Cohort Studies; Drug Resistance; Escherichia coli; Female; HIV Infections; Humans; Kenya; Malaria, Falciparum; Male; Middle Aged; Plasmodium falciparum; Prospective Studies; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Atovaquone; Female; HIV; HIV Infections; Humans; Immunohistochemistry; Pentamidine; Pneumocystis carinii; Pneumocystis Infections; Polymerase Chain Reaction; Spleen; Splenic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adenine; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Fluconazole; HIV Infections; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Organophosphonates; Oxazines; Positron-Emission Tomography; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Subacute central nervous system infection must be considered in any infant presenting with progressive encephalopathy. We present the case of an 18-month-old child with normal neuromotor development until the age of 14 months admitted for spastic hypertonia of the legs and arms associated with axial hypotonia. The mother reported that she recently had been found to be HIV-seropositive. HIV antibodies were negative during the first trimester of pregnancy. On the child's blood sample, the HIV test was positive associated with a major decrease in CD4 cell count. Viral load (ARN-PCR) was 720 copies par millilitre. On brain MRI, hypersignals were found in the white matter. HIV related encephalopathy caused by maternal fetal transmission was diagnosed. After 2 months of antiretroviral treatment (azidothymidine, lamivudine, and boosted lopinavir), the child's neurological condition improved. HIV infection must be suspected in all infants with progressive encephalopathy. The HIV test in pregnant women must be proposed at the beginning of pregnancy and repeated during the last trimester.

Topics: AIDS Dementia Complex; Anti-HIV Agents; Anti-Infective Agents; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; HIV Protease Inhibitors; HIV Seropositivity; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Lamivudine; Lopinavir; Polymerase Chain Reaction; Pyrimidinones; Reverse Transcriptase Inhibitors; RNA, Viral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Anti-Infective Agents; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumonia remains a concern for persons with long-standing HIV infection. We present a case of a 43-year-old HIV-infected woman with bilateral pneumonia whose presentation suggested the cause was a bacterial pathogen. A chest of radiograph and CT scan of the chest revealed infiltrates and adenopathies, but this did not help in the differential diagnosis. A Gram stain of a sputum specimen revealed gram-positive filamentous rods, and infection with Nocardia asteroides was diagnosed. The patient was started on a regimen of ceftriaxone and trimethoprim/sulfamethoxazole and experienced significant improvement within a few days.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Female; HIV Infections; Humans; Nocardia asteroides; Nocardia Infections; Pneumonia, Bacterial; Radiography; Sputum; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia is an opportunistic infection capable of causing life-threatening pneumonia in immunocompromised patients. To elucidate the clinical presentation and outcome of this disease in Taiwan, we analyzed the patients with P. jirovecii pneumonia during a 34-month period.. We collected data retrospectively from patients with P. jirovecii pneumonia at a medical center in northern Taiwan between January 2004 and October 2006. The diagnosis was made by nested polymerase chain reaction (PCR) analysis of expectorated sputum. Demographics, clinical characteristics, laboratory findings, and outcomes were compared between patients with and without human immunodeficiency virus (HIV) infection.. Forty nine patients were included in this study. The most common underlying diseases were HIV and malignancies. The mean (+/- standard deviation) age of the 49 patients was 54 +/- 20.2 years (range, 5 to 96 years). The mean CD4+ T-lymphocyte count was 110 cells/microL (range, 0-670 cells/microL). Although the mean CD4+ T-lymphocyte count of the non-HIV group was higher than that of the HIV group (165 +/- 78 cells/microL vs 57.5 +/- 97 cells/microL), statistical significance was not obtained (p=0.087). Arterial oxygenation (ratio of arterial oxygenation to fraction of inspired oxygen) was less than 200 mm Hg in 28 patients. Lactate dehydrogenase levels were higher than the normal range in 15 patients. A significantly higher proportion of patients died in the group without HIV compared with the HIV-infected patients (17/34 [50.0%] vs 1/15 [6.7%]; p=0.004).. P. jirovecii pneumonia remains a significant problem for immunocompromised patients. The mortality rate for patients without HIV infection was high (50%). Greater alertness with regard to early detection of P. jirovecii in HIV-negative immunosuppressed patients with the application of nested PCR may improve the clinical management and outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Chi-Square Distribution; Child; Child, Preschool; Female; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Retrospective Studies; Sputum; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The prevalence and cotrimoxazole susceptibility of Streptococcus pneumoniae isolated from sputum of 100 HIV-positive patients attending the Nigeria Institute of Medical Research clinic was investigated using standard microbiological methods. Eleven of the sputum specimens grew Streptococcus pneumoniae. Antimicrobial susceptibility test showed that all the isolates were sensitive to amoxicillin, augmentin, erythromycin and chloramphenicol but were resistant to cotrimoxazole. Continuous surveillance of S pneumoniae in sputum samples of HIV-positive subjects in this environment is necessary in order to regulate treatment regimen, considering that cotrimoxazole is the drug recommended by WHO for respiratory infections in HIV patients.

Topics: Adult; Anti-Infective Agents; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Nigeria; Pneumococcal Infections; Population Surveillance; Sputum; Streptococcus pneumoniae; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Female; HIV Infections; Humans; Hypopigmentation; Lamivudine; Nevirapine; Photosensitivity Disorders; Skin; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination

Isosporiasis, a rare cause of diarrhoea among HIV-infected patients in the pre-highly active antiretroviral therapy (HAART) era, seems to be re-emerging.. A retrospective study was carried out for the period 1995-2003 in two hospitals in Paris to describe the prevalence, clinical characteristics and therapeutic outcome of isosporiasis in HIV-infected patients, and to compare the findings with those for cryptosporidiosis and microsporidiosis.. The prevalence of isosporiasis increased from 0.4 per 1000 patients in the pre-HAART era (1995-1996) to 4.4 per 1000 patients in the HAART era (2001-2003), whereas the prevalence of cryptosporidiosis and microsporidiosis decreased. Compared with patients with either cryptosporidiosis (n=91) or microsporidiosis (n=58), patients with isosporiasis (n=28) more frequently originated from sub-Saharan Africa (72%), were more frequently female and heterosexual, and had a higher median CD4 count at diagnosis (142 cells/microL). All patients with isosporiasis presented with diarrhoea, which was severe enough to lead to hospital admission for 60% of them. Fever was uncommon (7%). All patients were treated for isosporiasis, 27 of them with cotrimoxazole. Relapse of isosporiasis occurred in six of 16 patients (38%) despite maintenance cotrimoxazole therapy and HAART.. Isosporiasis in France occurs mostly in patients emigrating from sub-Saharan Africa and can induce severe diarrhoea. Relapse is common despite cotrimoxazole maintenance therapy.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Diarrhea; Female; HIV Infections; Humans; Isosporiasis; Male; Middle Aged; Paris; Prevalence; Recurrence; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa.. In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing.. Among 856 participants (854 male, median age 41.5years, median CD4 290cells/mm(3)), 294 (34.3%) were receiving cotrimoxazole prophylaxis. Overall, 75/856 (8.8%) carried S. pneumoniae; among those taking vs. not taking cotrimoxazole, 8.2% vs. 9.1% were carriers. Risk factors for pneumococcal carriage were living with a child (adjusted OR 2.12, 95% CI 1.06-4.62) and recent hospitalisation (adjusted OR 1.80; 95% CI 0.98-3.30). Among participants not taking cotrimoxazole, the prevalence of carriage was higher in individuals with lower CD4 counts. Comparing participants taking cotrimoxazole vs. not, 60.9% vs. 22.4% (p=0.001) isolates were non-susceptible to cotrimoxazole and 30.4% vs. 8.2% were non-susceptible to penicillin (p=0.014). Thirty three/72 (45.8%) isolates were paediatric serotypes/groups. Nasopharyngeal compared with oropharyngeal swabs had higher sensitivity in detecting carriage (53/75, 70.7% vs. 31/75, 41.3%), and adding oropharyngeal sampling increased detection from 6.2% to 8.8%.. Non-susceptibility to cotrimoxazole and penicillin was more common among isolates from participants taking cotrimoxazole prophylaxis. Surveillance for antimicrobial susceptibility is important where prophylaxis is used. Treatment for pneumococcal disease should take into account a higher risk of non-susceptibility to antibiotics amongst individuals taking cotrimoxazole prophylaxis.

Topics: Adult; Anti-Bacterial Agents; Carrier State; CD4 Lymphocyte Count; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pharynx; Pneumococcal Infections; Risk Factors; Serotyping; South Africa; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (SXT) reduces morbidity and mortality among HIV-infected persons in Africa, but its impact on antimicrobial resistance is of concern.. HIV-uninfected (group A), HIV-infected but not requiring SXT (group B), and HIV-infected and eligible for SXT (group C) adults were recruited into a prospective observational cohort study in Moshi, Tanzania. Stool was examined for Escherichia coli nonsusceptible to SXT at baseline and at weeks 1, 2, 4, and 24. General estimating equation models were used to assess differences in susceptibility over time and cross-resistance to other antimicrobials.. Of 181 subjects, 118 (65.1%) were female and the median (range) age was 36 (20 to 72) years. At baseline, E. coli nonsusceptible to SXT was isolated from 23 (53.5%) of 43 patients in group A, 25 (67.6%) of 37 patients in group B, and 37 (64.9%) of 57 patients in group C. The odds ratios (P value) for SXT nonsusceptibility in group C at weeks 1, 2, 4, and 24 compared with baseline were 3.4 (0.013), 3.0 (0.019), 2.9 (0.030), and 1.5 (0.515), respectively. SXT nonsusceptibility was associated with nonsusceptibility to ampicillin, chloramphenicol, ciprofloxacin, and nalidixic acid (P

Topics: Adult; Aged; Anti-Infective Agents; Drug Resistance, Bacterial; Escherichia coli; Feces; Female; HIV Infections; Humans; Male; Middle Aged; Tanzania; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

To estimate the burden of HIV disease in Uganda and the effect of HIV/AIDS control programmes to mitigate it.. Mathematical modelling and projecting using surveillance and census data.. Using antenatal clinic surveillance (1986-2002) and a recent population-based survey (2004-2005) data, we modelled the adult national HIV prevalence over time (1981-2004), and kept prevalence constant at 6.4% for the years 2004-2010. Using Spectrum software and census data, we estimated the national burden of HIV disease and the effect of selected HIV-related prevention and treatment programmes.. In 2005, we estimated that there were 135,300 new HIV infections (adult HIV incidence 0.96%), 691,900 asymptomatic prevalent infections, 88 100 AIDS cases, and 76 400 AIDS deaths. An estimated 647,000 (80%) HIV-infected adults were unaware of their infection; one third of all adult deaths were HIV related. As a result of population growth, by 2008 a similar number of people will be HIV infected (1.1 million) as during the peak of the epidemic in 1994. Although antiretroviral therapy (ART) coverage is expected to rise from 67,000 (2005) to 160,000 (2010), the number of persons needing but not receiving ART will decrease only slightly from 127,600 (2005) to 111,100 (2010). The use of single-dose in 2005 nevirapine probably averted only 4% of the estimated 20 400 vertical infections.. HIV/AIDS continues to be a leading cause of adult disease and death in Uganda. Universal ART access is probably unachievable. With the absolute burden of HIV disease approaching the historic peak in the early 1990s, more effective prevention programmes are of paramount importance.

Topics: Adolescent; Adult; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Child; Cost of Illness; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Health facilities providing tuberculosis (TB) treatment in two districts in rural western Kenya with a high TB and human immunodeficiency virus (HIV) burden.. To evaluate TB and HIV/acquired immune-deficiency syndrome (AIDS) services at the facilities and identify barriers to providing quality diagnostic HIV testing and counseling (DTC) and HIV treatment for TB patients in anticipation of the introduction of TB-HIV collaborative services.. We performed a standard interview with health workers responsible for TB care, inspected the facilities and collected service delivery data. A self-administered questionnaire on training attended was given to all health workers. Results were shared with stakeholders and plans for implementation were developed.. Of the 59 facilities, 58 (98%) provided TB treatment, 19 (32%) offered sputum microscopy and 24 (41%) HIV testing. Most facilities (72%) advised HIV testing only if TB patients were suspected of having AIDS. Barriers identified included unaccommodating TB clinic schedules and lack of space, which was an obstacle to holding confidential discussions. The need to refer for HIV testing and/or HIV care was a perceived barrier to recommending these services. Activities implemented following the assessment aimed 1) to provide HIV testing and cotrimoxazole prophylaxis at all TB treatment clinics, 2) to increase availability of HIV treatment services, and 3) to address structural needs at each facility.. This evaluation identified barriers to the implementation of HIV testing and care services within facilities providing TB treatment.

Topics: AIDS Serodiagnosis; Ambulatory Care; Anti-Infective Agents; Community Health Services; Directive Counseling; Facility Design and Construction; Health Services Accessibility; HIV Infections; Humans; Kenya; Program Evaluation; Rural Health Services; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Integrated tuberculosis (TB) and human immunodeficiency virus (HIV) services in a resource-constrained setting.. Pilot provider-initiated HIV testing and counselling (PITC) for TB patients and suspects.. Through partnerships, resources were mobilised to establish and support services. After community sensitisation and staff training, PITC was introduced to TB patients and then to TB suspects from December 2003 to December 2005.. Of 5457 TB suspects who received PITC, 89% underwent HIV testing. Although not statistically significant, TB suspects with TB disease had an HIV prevalence of 61% compared to 63% for those without. Of the 614 suspects who declined HIV testing, 402 (65%) had TB disease. Of 2283 patients referred for cotrimoxazole prophylaxis, 1951 (86%) were enrolled, and of 1727 patients assessed for antiretroviral treatment (ART), 1618 (94%) were eligible and 1441 (83%) started treatment.. PITC represents a paradigm shift and is feasible and acceptable to TB patients and TB suspects. Clear directives are nevertheless required to change practice. When offered to TB suspects, PITC identifies large numbers of persons requiring HIV care. Community sensitisation, staff training, multitasking and access to HIV care contributed to a high acceptance of HIV testing. Kenya is using this experience to inform national response and advocate wide PITC implementation in settings faced with the TB-HIV epidemic.

Topics: AIDS Serodiagnosis; Anti-HIV Agents; Anti-Infective Agents; Delivery of Health Care, Integrated; Directive Counseling; HIV Infections; Humans; Kenya; Patient Acceptance of Health Care; Pilot Projects; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Kinshasa, Democratic Republic of Congo.. To evaluate the implementation of three models of provider-initiated HIV counseling and testing (CT) for tuberculosis (TB) patients.. HIV CT was offered to all TB patients aged > or =18 months registered for treatment at three project clinics between August 2004 and June 2005. HIV CT was performed at the TB clinic, the health center or the freestanding voluntary counseling and testing (VCT) center. HIV-infected patients received cotrimoxazole prophylaxis.. Uptake of HIV CT was high (95-98%) when performed at the TB clinic or primary health care center, but significantly lower (68.5%) among patients referred to a free-standing VCT center. The overall HIV prevalence among the 1088 patients tested for HIV was 18.8%. HIV was associated with female sex (aOR 1.91), recurrent TB (aOR 2.74), extra-pulmonary TB (aOR 1.97) and age.. Implementation of provider-initiated routine HIV CT by the TB nurse or health care worker at the primary health care center results in a higher uptake compared to referral of patients with TB to freestanding VCT clinics. Provider-initiated HIV CT is only a first step and needs to be linked to access to HIV care, support and treatment.

Topics: Adolescent; Adult; Age Factors; AIDS Serodiagnosis; Ambulatory Care; Anti-Infective Agents; Child; Child, Preschool; Democratic Republic of the Congo; Directive Counseling; Female; HIV Infections; Humans; Infant; Male; Prevalence; Recurrence; Referral and Consultation; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Voluntary Programs

Topics: Adult; Antimalarials; Antiretroviral Therapy, Highly Active; Bedding and Linens; Child; Cost-Benefit Analysis; HIV Infections; Home Care Services; Humans; Insecticides; Malaria; Rural Health Services; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Antiretroviral therapy (ART) is increasingly available in Africa, but physicians and clinical services are few. We therefore assessed the effect of a home-based ART programme in Uganda on mortality, hospital admissions, and orphanhood in people with HIV-1 and their household members.. In 2001, we enrolled and followed up 466 HIV-infected adults and 1481 HIV-uninfected household members in a prospective cohort study. After 5 months, we provided daily co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) prophylaxis to HIV-infected participants. Between May, 2003, and December, 2005, we followed up 138 infected adults who were eligible and 907 new HIV-infected participants and their HIV-negative household members in a study of ART (mainly stavudine, lamivudine, and nevirapine). Households were visited every week by lay providers, and no clinic visits were scheduled after enrolment. We compared rates of death, hospitalisation, and orphanhood during different study periods and calculated the number needed to treat to prevent an outcome.. 233 (17%) of 1373 participants with HIV and 40 (1%) of 4601 HIV-uninfected household members died. During the first 16 weeks of ART and co-trimoxazole, mortality in HIV-infected participants was 55% lower than that during co-trimoxazole alone (14 vs 16 deaths per 100 person-years; adjusted hazard ratio 0.45, 95% CI 0.27-0.74, p=0.0018), and after 16 weeks, was reduced by 92% (3 vs 16 deaths per 100 person-years; 0.08, 0.06-0.13, p<0.0001). Compared with no intervention, ART and co-trimoxazole were associated with a 95% reduction in mortality in HIV-infected participants (5 vs 27 deaths per 100 person-years; 0.05, 0.03-0.08, p<0.0001), 81% reduction in mortality in their uninfected children younger than 10 years (0.2 vs 1.2 deaths per 100 person-years; 0.19, 0.06-0.59, p=0.004), and a 93% estimated reduction in orphanhood (0.9 vs 12.8 per 100 person-years of adults treated; 0.07, 0.04-0.13, p<0.0001).. Expansion of access to ART and co-trimoxazole prophylaxis could substantially reduce mortality and orphanhood among adults with HIV and their families living in resource-poor settings.

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Child; Child Mortality; Child, Orphaned; Female; HIV Infections; HIV Seronegativity; HIV-1; Hospitalization; Humans; Male; Prospective Studies; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Unprotected sex (UPS) among persons receiving highly active antiretroviral therapy (HAART) remains a concern because of the risk of HIV-transmission. A cross-sectional study comparing the sexual risk behaviour of 179 people living with HIV/AIDS (PLHA) receiving HAART with that of 143 PLHA receiving preventive therapy (PT) with cotrimoxazole/isoniazid was conducted in Mombasa, Kenya. Forty-five percent of all participants were sexually active in the last six months. Participants receiving PT were more likely to report > or =2 partners (13% vs.1%; P = 0.006). Participants receiving PT reported more UPS with regular partners (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 1.8-8.4) and also more sexually transmitted infections (STI) symptoms (OR: 1.7; 95% CI: 1.0-2.8; P = 0.059). More than 40% of all participants did not know the HIV-status of regular partners. Therefore, HAART was not associated with increased sexual risk behaviours though considerable risk of HIV-transmission remains. HIV-care services need to emphasize partner testing and consistent condom use with all partners.

Topics: Adult; Antiretroviral Therapy, Highly Active; Condoms; Cross-Sectional Studies; Female; HIV Infections; Humans; Isoniazid; Kenya; Male; Odds Ratio; Risk-Taking; Sexual Behavior; Sexual Partners; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia, as implementation at the local health centre level has yet to be undertaken in many resource-limited countries despite recommendations in recent updated World Health Organization (WHO) guidelines.. A probabilistic decision analytical model of HIV/AIDS progression in children based on the CD4 cell percentage (CD4%) was populated with data from the placebo-controlled Children with HIV Antibiotic Prophylaxis trial that had reported a 43% reduction in mortality with cotrimoxazole prophylaxis in HIV-infected children aged 1-14 years.. Unit costs (US$ in 2006) were measured at University Teaching Hospital, Lusaka. Cost-effectiveness expressed as cost per life-year saved, cost per quality adjusted life-year (QALY) saved, cost per disability adjusted life-year (DALY) averted was calculated across a number of different scenarios at tertiary and primary healthcare centres.. : Cotrimoxazole prophylaxis was associated with incremental cost-effectiveness ratios (ICERs) of US$72 per life-year saved, US$94 per QALY saved and US$53 per DALY averted, i.e. substantially less than a cost-effectiveness threshold of US$1019 per outcome (gross domestic product per capita, Zambia 2006). ICERs of US$5 or less per outcome demonstrate that cotrimoxazole prophylaxis is even more cost-effective at the local healthcare level. The intervention remained cost-effective in all sensitivity analyses including routine haematological and CD4% monitoring, varying starting age, AIDS status, cotrimoxazole formulation, efficacy duration and discount rates.. Cotrimoxazole prophylaxis in HIV-infected children is an inexpensive low technology intervention that is highly cost-effective in Zambia, strongly supporting the adoption of WHO guidelines into essential healthcare packages in low-income countries.

Topics: Adolescent; Child; Child, Preschool; Cost-Benefit Analysis; Developing Countries; Drug Costs; Female; Follow-Up Studies; HIV; HIV Infections; Humans; Infant; Male; Markov Chains; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Topics: Africa; Anti-Bacterial Agents; Child; Cost-Benefit Analysis; Developing Countries; HIV; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Kenya, one of the 22 tuberculosis (TB) high-burden countries, whose TB burden is fuelled by the human immunodeficiency virus (HIV).. To monitor and evaluate the implementation of HIV testing and provision of HIV care to TB patients in Kenya through the establishment of a routine TB-HIV integrated surveillance system.. A descriptive report of the status of implementation of HIV testing and provision of HIV interventions to TB patients one year after the introduction of the revised TB case recording and reporting system.. From July 2005 to June 2006, 88% of 112835 TB patients were reported to the National Leprosy and TB Control Programme, 98773 (87.9%) of whom were reported using a revised recording and reporting system that included TB-HIV indicators. HIV testing of TB patients increased from 31.5% at the beginning of this period to 59% at the end. Of the 46428 patients tested for HIV, 25558 (55%) were found to be HIV-positive, 85% of whom were provided with cotrimoxazole preventive treatment and 28% with antiretroviral treatment.. A country-wide integrated TB-HIV surveillance system in TB patients can be implemented and provides essential data to monitor and evaluate TB-HIV related interventions.

Topics: Adolescent; Adult; Aged; AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Child; Child, Preschool; Counseling; Female; HIV Infections; Humans; Infant; Infant, Newborn; Kenya; Male; Middle Aged; Patient Care; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

There is little information on nasopharyngeal (NP) flora or bacteremia in HIV-infected children. Our aim was to describe the organisms and antimicrobial resistance patterns in children enrolled in a prospective study comparing daily and three times weekly trimethoprim-sulfamethoxazole (TMP-SMX) and isoniazid (INH) or placebo prophylaxis.. NP swabs were taken at baseline from HIV-infected children enrolled in the study. Standard microbiological techniques were used. Children were grouped according to previous or current exposure to TMP-SMX and whether enrolled to the study during a period of hospitalization. Blood culture results were also recorded within 12 months of baseline.. Two hundred and three children, median age 1.8 (Interquartile [IQ]: 0.7-4) years had NP swabs submitted for culture. One hundred and eighty-four (90.7%) had either stage B or C HIV disease. One hundred and forty-one (69.8%) were receiving TMP-SMX and 19 (9.4%) were on antiretroviral therapy. The majority, 168 (82%) had a history of hospitalization and 91 (44.8%) were enrolled during a period of hospitalization. Thirty-two subjects (16.2%) died within 12 months of study entry. One hundred and eighty-one potential pathogens were found in 167 children. The most commonly isolated organisms were Streptococcus pneumoniae (48: 22.2%), Gram-negative respiratory organisms (Haemophilus influenzae and Moraxella catarrhalis) (47: 21.8%), Staphylococcus aureus (44: 20.4%), Enterobacteriaceae 32 (14.8%) and Pseudomonas 5 (2.3%). Resistance to TMP-SMX occurred in > 80% of pathogens except for M. catarrhalis (2: 18.2% of tested organisms). TMP-SMX resistance tended to be higher in those receiving it at baseline (p = 0.065). Carriage of Methicillin resistant S. aureus (MRSA) was significantly associated with being on TMP-SMX at baseline (p = 0.002). Minimal inhibitory concentrations (MIC) to penicillin were determined for 18 S. pneumoniae isolates: 7 (38.9%) were fully sensitive (MIC or=2 microg/ml). Fifty percent of Enterobacteriaceae produced extended spectrum beta-lactamases (ESBL) (resistant to third generation cephalosporins) and 56% were resistant to gentamicin. Seventy-seven percent of S. aureus were MRSA. Carriage of resistant organisms was not associated with hospitalization.On multivariate logistic regression, risk factors for colonization with Enterobacteriaceae were age

Topics: Anti-Infective Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Carrier State; Child; Child, Preschool; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; HIV Infections; Humans; Incidence; Infant; Isoniazid; Logistic Models; Male; Methicillin Resistance; Nasopharynx; Prospective Studies; Risk Factors; South Africa; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; Infusions, Intravenous; Neurosyphilis; Penicillins; Syphilis, Cutaneous; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the incidence of Isospora belli infection in HIV-infected patients in France, and to study risk factors.. The French Hospital Database on HIV (FHDH) is a prospective cohort study that collects demographic, clinical and therapeutic data on patients managed in 62 hospitals. We reviewed all cases of I. belli infection recorded between 1992 and 2003. We compared the incidence in 1992-1994 [before the use of dual therapy and combination antiretroviral therapy (cART)] and in 1997-2003 (when use of cART was widespread), after stratification for CD4 cell count (< 50, 50-99, 100-199 and > 200 cells/microL).. A total of 164 patients had I. belli infection either at enrollment (n=71) or during follow up (n=93). During the study period, I. belli infection tended to occur less frequently during follow up, and to be diagnosed mainly at database enrollment. The incidence of I. belli infection during follow up fell by 79% [relative hazard (RH) 0.21; 95% confidence interval (CI) 0.13-0.33] in the cART period compared with the pre-cART period; no such change was noted among patients with CD4 cell counts below 50 cells/microL. In multivariable analysis, the risk of I. belli infection was significantly higher among patients from sub-Saharan Africa (RH 4.3; 95% CI 2.6-7.3). After adjustment for CD4 cell count, patients receiving cotrimoxazole prophylaxis were found to be at a lower risk of I. belli infection (RH 0.3; 95% CI 0.2-0.6).. In France, I. belli infection among HIV-infected patients is now mainly seen in patients from sub-Saharan Africa, who present at an advanced stage.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Databases, Factual; Drug Therapy, Combination; Female; France; HIV Infections; HIV-1; Humans; Incidence; Intestinal Diseases, Parasitic; Isosporiasis; Male; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardia asteroides was isolated after prolonged culture from the pericardial fluid of a human immunodeficiency virus-infected patient. The lengthy duration required for culture growth and identification of this N. asteroides isolate affected both initial therapeutic decisions and patient management. A proposed algorithm for the microbiological workup of pericardial fluid for possible Nocardia spp. is described in an effort to improve the timeliness of results.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; HIV Infections; Humans; Male; Nocardia asteroides; Nocardia Infections; Pericarditis; Trimethoprim, Sulfamethoxazole Drug Combination

Mortality is high in HIV-infected TB patients, but few studies from Southeast Asia have documented the benefits of interventions, such as co-trimoxazole (CTX), in reducing mortality during TB treatment. To help guide policy in Vietnam, we studied the epidemiology of HIV-associated TB in one province and examined factors associated with outcomes, including the impact of CTX use.. We retrospectively abstracted data for all HIV-infected persons diagnosed with TB from 2001-2004 in An Giang, a province in southern Vietnam in which TB patients receive HIV counseling and testing. We used standard WHO definitions to classify TB treatment outcomes. We conducted multivariate analysis to identify risk factors for the composite outcome of death, default, or treatment failure during TB treatment. From 2001-2004, 637 HIV-infected TB patients were diagnosed in An Giang. Of these, 501 (79%) were male, 321 (50%) were aged 25-34 years, and the most common self-reported HIV risk factor was sex with a commercial sex worker in 221 (35%). TB was classified as smear-positive in 531 (83%). During TB treatment, 167 (26%) patients died, 9 (1%) defaulted, and 6 (1%) failed treatment. Of 454 patients who took CTX, 116 (26%) had an unsuccessful outcome compared with 33 (70%) of 47 patients who did not take CTX (relative risk, 0.4; 95% confidence interval [CI], 0.3-0.5). Adjusting for male sex, rural residence, TB smear status and disease location, and the occurrence of adverse events during TB treatment in multivariate analysis, the benefit of CTX persisted (adjusted odds ratio for unsuccessful outcome 0.1; CI, 0.1-0.3).. In An Giang, Vietnam, HIV-associated TB was associated with poor TB treatment outcomes. Outcomes were significantly better in those taking CTX. This finding suggests that Vietnam should consider applying WHO recommendations to prescribe CTX to all HIV-infected TB patients.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Cohort Studies; Female; HIV; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Vietnam; Young Adult

Studies in developed countries have shown highly active antiretroviral therapy (HAART) decreases incidence of severe opportunistic diseases (ODs) in HIV-infected patients beyond that which is expected from changes in CD4+ T-cell count.. To estimate the independent impact of HAART on reducing ODs and mortality in Côte d'Ivoire.. Within two longitudinal studies of HIV-infected adults (1996-2003), we identified time on 'cotrimoxazole alone' and 'HAART plus cotrimoxazole' WHO stage 3-4 defining events and severe malaria were divided into those preventable and not preventable with cotrimoxazole. Incidence of ODs by CD4 count stratum was estimated using incidence density analysis. CD4+ T-cell count at time of OD was estimated using linear interpolation. Using Poisson regression, we estimated the effect of HAART on OD incidence and mortality by CD4 count stratum.. Totals of 446 and 135 adults were followed during 6,216 and 3,412 person-months in the cotrimoxazole alone and HAART plus cotrimoxazole periods, respectively. There was a CD4+ T-cell-independent risk reduction for ODs and mortality during the HAART plus cotrimoxazole period compared with cotrimoxazole alone, which varied by time on HAART, CD4 count stratum and OD type. It was mainly seen after 6 months on HAART and for ODs not preventable by cotrimoxazole. The HAART effect differed significantly by CD4 count stratum (P=0.02), but was significant in all strata after 6 months on HAART.. In these sub-Saharan African adults, HAART initiation reduced ODs and mortality beyond that which was expected through the HAART-induced CD4+ T-cell increase. Further studies should examine practical implications of this independent 'HAART effect' on clinical outcomes in patients on HAART.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Bacterial Infections; CD4 Lymphocyte Count; Cote d'Ivoire; Drug Therapy, Combination; HIV Infections; Humans; Incidence; Malaria; Mycoses; Poisson Distribution; Severity of Illness Index; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis and insecticide-treated bednets reduce malaria risk among HIV-infected adults. The efficacy of TMP/SMX may be diminished where antifolate resistance to malaria is high. We evaluated the efficacy of these interventions for malaria prevention among Ugandan children.. We concurrently followed 300 HIV-infected children aged 1-10 years and a community-based cohort of 561 healthy children aged 1-11 years over 11 months in Kampala, Uganda. The HIV-infected children received TMP/SMX prophylaxis and insecticide treated bednets. In the community cohort, insecticide-treated bednets were introduced during the observation period. Children from both cohorts were followed using a standardized protocol to measure the incidence of malaria.. Only nine episodes of malaria were diagnosed among HIV-infected children (incidence = 0.07/person-year) in comparison with 440 episodes among children from the community (incidence = 0.90/person-year; P < 0.0001). The use of insecticide-treated bednets was associated with a 43% reduction in malaria incidence (P < 0.001), and a combination of TMP/SMX and use of insecticide-treated bednets with a 97% reduction in malaria incidence (P < 0.001). The prevalence of five mutations associated with antifolate resistance was high among malaria cases detected in both the HIV (100%) and community cohorts (75%). Malaria accounted for only 4% of febrile episodes in the HIV cohort in comparison with 33% in the community-based cohort (P < 0.0001).. In a malaria endemic area with a high level of molecular markers of antifolate resistance, the combined use of TMP/SMX prophylaxis and insecticide-treated bednets was associated with a dramatic reduction in malaria incidence among HIV-infected children.

Topics: Antimalarials; Bedding and Linens; Case-Control Studies; Child; Child, Preschool; Female; HIV Infections; Humans; Incidence; Infant; Insecticides; Longitudinal Studies; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

To determine whether Malawi antiretroviral treatment (ART) clinics providing cotrimoxazole (CTX) prophylaxis had lower early mortality rates compared with clinics not providing CTX.. Retrospective cohort study of eleven ART clinics in Malawi that were or were not providing CTX. Medical record abstraction was performed for all patients (N = 1295) initiating ART between July 1 and December 15, 2005. At 5 ART sites, CTX was given to patients dosed at 960 mg daily or 480 mg twice a day (according to national guidelines).. When all defaults (patients lost to follow-up for >90 days) were excluded from the analysis, the 6-month mortality rate was 10.7% in patients receiving ART at CTX clinics compared with 18.0% in those not at CTX clinics (6-month mortality risk reduction = 40.7%; P = 0.0013). Kaplan-Meier survival curves for patients receiving CTX and patients not receiving CTX were significantly different; survival differences were apparent as early as 40 to 45 days after initiation of ART.. Patients receiving ART in Malawi at clinics offering CTX prophylaxis had significantly reduced mortality during the first 6 months of ART. This additional intervention may have the potential to improve the lives of patients on ART, because CTX is readily available and relatively inexpensive and can, in principle, be easily introduced into ART delivery programs.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Cohort Studies; Dose-Response Relationship, Drug; Female; HIV Infections; Humans; Malawi; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Haematological anomalies are frequent during HIV infection, and can be the fact of virus and or bone marrow toxicity of antiretroviral drugs. In order to analyze the evolution of the haematological parameters during HAART this work was carried out in the internal medicine department of the national teaching hospital Yalgado-Ouédraogo in Ouagadougou. So 107 patients receiving for the first time HAART and followed regularly were retained. The immunological efficacy at the end of the first six months was 60, 75% with an average gain of 119 CD4/mm3. The haematological changes at the end of these first six months showed: --an anaemia in 51.4% of the cases at month 6 versus 80.3% at baseline (p=0.0001). The average rate of haemoglobin was 11.8 versus 11.2 g/dl at baseline in the AZT containing HAART regimen (p=0.014) and 12.2 versus 10.7 g/dl at baseline in the group without AZT (p=0.00006). --a neutropenia in 35.5% of the cases at month 6 versus 31.7% at baseline (p=0.6). The average rate of neutrophil was 1908/mm3 versus 2267.1/mm3 at baseline in the AZT containing HAART regimen and 2150.7/mm3 versus 2001.9/mm3 at baseline in the group without AZT These results show that the therapeutic efficacy measured on the immunological answer is accompanied by a reduction of haematological anomalies. They also suggest the necessity to evaluate the cotrimoxazole impact before deciding the interruption of AZT.

Topics: Adolescent; Adult; Anemia; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Burkina Faso; Female; Follow-Up Studies; Hematologic Diseases; Hemoglobins; HIV Infections; Humans; Lymphopenia; Male; Middle Aged; Neutropenia; Retrospective Studies; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Adult; Anti-Retroviral Agents; Dandy-Walker Syndrome; Female; Heart Ventricles; HIV Infections; Humans; Infant, Newborn; Lamivudine; Male; Nevirapine; Pregnancy; Prenatal Exposure Delayed Effects; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Blood Cell Count; CD4 Lymphocyte Count; Hemoglobins; HIV Infections; Humans; Leukocyte Count; Lymphocyte Count; Platelet Count; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Mycotic aneurysms are associated with high mortality rates and are managed in the local setting with extra-anatomical bypass followed by ligation, exclusion and debridement of the aneurysm. This is the first case of successful endovascular stenting in an immunocompromised patient with Salmonella mycotic aneurysm.. A middle-aged man who was HIV positive had Salmonella septicaemia. He developed abdominal pain 5 days after admission and a computed tomography (CT) scan of the abdomen revealed infrarenal aortitis. He developed a mycotic aneurysm 3 weeks later.. He opted for endovascular stenting and after prolonged antibiotic therapy and negative blood cultures, he underwent the procedure using a Talent stent, with an iliac extension.. He was discharged 1 week after stenting and maintained on oral bactrim based on sensitivity. At 1-year follow-up, he remains well symptomatically and CT scan showed no endoleak or collection.. Endovascular stenting, though a fairly new procedure, can be successfully deployed even in a mycotic aneurysm in the right setting.

Topics: Aneurysm, Infected; HIV Infections; Humans; Male; Middle Aged; Salmonella enteritidis; Salmonella Infections; Stents; Trimethoprim, Sulfamethoxazole Drug Combination

As HIV/AIDS drugs are becoming more widely available in Southern Africa, we compared the effectiveness and cost effectiveness of different treatment options, using a Markov Monte Carlo simulation model based on published estimates of disease progression, treatment effectiveness and health care costs. Cost and outcome values were discounted. Quality of life was considered. Acceptability curves summarized uncertainties. Sensitivity analyses tested assumptions. Results showed that triple antiretroviral therapy (ARV) plus antibiotics would prolong life by 6.7 undiscounted years if provided 'late' (CD4 = 200 cells/microl) and by 9.8 years if provided 'early' (CD4 = 350 cells/microl). The incremental undiscounted costs per year of life gained, compared to no preventive therapy, were $17 for isoniazid plus cotrimoxazole started late, $244 for both antibiotics started early, $2454 for ARV plus antibiotics started late and $2784 for ARV plus both antibiotics started early. The discounted incremental costs per quality adjusted life year (QALY) gained were, respectively, $29 saving, $254, $4937 and $3057. Late ARV plus both antibiotics was the strategy most likely to be cost effective if society was willing to pay more than $2000 per life year gained. Cost-effectiveness estimates were sensitive to discounting and assumed treatment costs but were less sensitive to assumed treatment effectiveness.

Topics: Africa, Southern; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Antitubercular Agents; Cost-Benefit Analysis; Drug Therapy, Combination; Health Care Costs; HIV Infections; Humans; Isoniazid; Markov Chains; Models, Statistical; Monte Carlo Method; Quality-Adjusted Life Years; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

A retrospective review was performed of patients diagnosed with Pneumocystis carinii pneumonia (PCP) from 1994 to 2003 at the Prince of Wales Hospital in Hong Kong. Eighteen patients were identified. Six (33.3%) were co-infected with human immunodeficiency virus (HIV). The remaining 12 non-HIV-infected patients had underlying diseases: three post-renal transplant recipients, three with haematological malignancies, two with auto-immune diseases, two with renal diseases, one with hepatocellular carcinoma and one with congenital cytomegalovirus disease. Cytomegalovirus co-infection was observed in four patients. All patients received cotrimoxazole therapy, with intolerance observed in four of them, including one with glucose-6-phosphate dehydrogenase deficiency, two with repeated vomiting and one with renal impairment. Overall crude mortality was 33.3%. The results suggested that, apart from being a common infection for patients with HIV infection, PCP can occur during the course of many immunosuppressive diseases and therapies. The mortality of PCP was high despite appropriate treatment. Chemoprophylaxis should be considered in populations at risk.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Child; Child, Preschool; Female; HIV Infections; Hong Kong; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We followed a cohort of 592 HIV-infected adults during 1292 person-years in Abidjan before the highly active antiretroviral therapy (HAART) era. On the basis of the exhaustive monitoring of nonantiretroviral drugs actually delivered to the patients and of the real cost of drugs at the cohort center's pharmacy during the study period, we estimated the mean cost of drugs per person per year (MCPPY) overall, by drug characteristics, and by patients' baseline CD4 cell count. The MCPPY was dollar 198 US overall and dolalr 83 US, dollar 101 US, dollar 186 US, dollar 233 US, and dollar 459 US in patients with a baseline CD4 count > or = 500 cells/mm, 350 to 499 cells/mm, 200 to 349 cells/mm, 100 to 199 cells/mm, and <100 cells/mm, respectively. The most costly classes of drugs were the antibacterial (MCPPY dollar 30 US), the antifungal (dollar 16 US), and the analgesic (dollar 6 US) classes in patients with a baseline CD4 count > or = 500 cells/mm versus the antifungal (dollar 208 US), the antibacterial (dollar 49 US), and the antiparasitic (dollar 31 US) classes in patients with a baseline CD4 count <100 cells/mm. These data could be used in further cost-effectiveness analyses that seek to prioritize health interventions. Meanwhile, they roughly suggest that successful antiretroviral treatment, which would stabilize the CD4 count above 500 cells/mm, could reduce by 5-fold the cost of nonantiretroviral drugs in HIV-infected adults in Abidjan.

Topics: Adult; Anti-Infective Agents; CD4 Lymphocyte Count; Cohort Studies; Cote d'Ivoire; Delivery of Health Care; Drug Costs; Female; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Codon; Dihydropteroate Synthase; DNA, Fungal; Drug Resistance, Fungal; Germany; HIV Infections; Humans; Immunocompromised Host; Lymphoma, T-Cell; Pneumocystis carinii; Pneumonia, Pneumocystis; Point Mutation; Trimethoprim, Sulfamethoxazole Drug Combination

In a placebo-controlled trial of co-trimoxazole prophylaxis in Côte d'Ivoire, neutropenia was the most frequent short-term side effect. The long-term incidence of neutropenia in sub-Saharan African adults receiving co-trimoxazole has never been reported. We followed a prospective cohort of HIV-infected adults receiving co-trimoxazole (sulphamethoxazole 800 mg/trimethoprim 160 mg daily) in Abidjan. Grades of neutropenia were successively defined as at least one absolute neutrophil count (ANC) of: <1500/mm(3) (severity grade >/=1), <1000/mm(3) (grade >/=2), <750/mm(3) (grade >/=3) or <500/mm(3) (grade 4). In total, 533 adults were followed-up during 1450 person-years, with a total of 3154 ANCs. The probability of remaining free of neutropenia at 48 months was 0.29 (95% CI 0.23-0.34) for grade >/=1, 0.64 (95% CI 0.60-0.71) for grade >/=2, 0.82 (95% CI 0.77-0.86) for grade >/=3 and 0.96 (95% CI 0.93-0.99) for grade 4. The only factor significantly associated with a higher rate of all grades of neutropenia was a low baseline CD4 count. There was no association between any grade of neutropenia and the global risk of serious morbidity during the study period. In adults receiving co-trimoxazole in Abidjan, mild neutropenia is a common observation with no evidence of negative clinical consequences. The consequences of associating co-trimoxazole with other haematotoxic drugs should be carefully assessed.

Topics: Adult; Anti-Infective Agents; Cote d'Ivoire; Female; HIV Infections; Humans; Incidence; Male; Neutropenia; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment.

Topics: Adolescent; Anti-HIV Agents; Chemoprevention; Child; Child, Preschool; Data Collection; Developing Countries; Female; HIV Infections; Humans; Infant; Infant, Newborn; Male; Needs Assessment; Program Evaluation; Trimethoprim, Sulfamethoxazole Drug Combination; United Nations; World Health Organization

The objective of this study was to determine the financial incentives that companies have to treat HIV-infected employees, in a health care services company in Kampala, Uganda.. Cost-benefit analysis from the company's perspective of three interventions to treat HIV-infected employees.. The costs and benefits of each intervention were compared with no intervention and with each other: cotrimoxazole prophylaxis (CTX) starting at WHO stage 2; highly active antiretroviral therapy (HAART) plus CTX starting at WHO stage 2; and a 'hybrid' strategy that begins with CTX at WHO stage 2 and later includes HAART. The 5-year health and economic outcomes were calculated using a Markov model. Inputs for disease progression rates and effects of HIV on company costs were derived from published and unpublished data and a survey administered to company officers.. The analysis showed that the 'hybrid' intervention is the most cost-effective. For 100 skilled employees it would save the company 38,939 US dollars and 73 disability adjusted life-years (DALYs). For unskilled workers 'CTX' is the most cost effective and would save 16,417 US dollars and 60 DALYs. 'Hybrid' has an incremental cost-effectiveness ratio of 45 US dollars per DALY for unskilled workers whereas HAART is far less economical at an incremental cost per DALY of 4118 US dollars. For 'CTX', net savings are preserved across the full range of input values.. A 'hybrid' intervention combining CTX prophylaxis followed by HAART would generate savings to a Ugandan company. Governments and other donors may find opportunities to share costs with the private sector as part of their phase-in strategy for antiretroviral therapy.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cost of Illness; Cost-Benefit Analysis; Drug Costs; Employer Health Costs; HIV Infections; Humans; Models, Econometric; Occupational Health Services; Private Sector; Sensitivity and Specificity; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Topics: Anti-Infective Agents; Family Health; HIV Infections; Humans; Mortality; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this trial was to test a simple method of measuring and identifying non-compliance with antiretroviral (ARV) therapy and cotrimoxazole (CTX) prophylaxis in a resource-limited setting. A cross-sectional study was undertaken among HIV patients attending two outpatient clinics in Bangui, Central African Republic. Compliance with ARV and CTX treatment was assessed based on 5 measurement modalities, i.e., skipping medication during the 4 days prior to attendance, attendance assiduity, number of remaining tablets, patient visual analogue scale (VAS), and physician VAS. These measures were combined to obtain an overall medication compliance score. A total of 141 patients were interviewed including 89 using ARV and 52 using CTX. Compliance scores varied according to measurement modality from 66.3% to 96.6% for ARV and from 67.3% to 90.4% for CTX. The only significant difference between patients using ARV and CTX involved physician VAS that was significantly lower for CTX than ARV (p=0.04). Overall medication compliance scores classified 117 patients (83%) as compliant and 21 patients (17%) as non-compliant. According to this study the level of medication compliance was relatively good (83%). Findings also indicated that measurement of compliance was feasible using a combination of remaining tablet count and assessment of medication skipping in the last 4 or 7 days. Routine clinical use of these modalities allows assessment and improvement of medication compliance.

Topics: Anti-Retroviral Agents; Central African Republic; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Patient Compliance; Trimethoprim, Sulfamethoxazole Drug Combination

HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets.. In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season.. 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056).. A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; Bedding and Linens; Female; HIV Infections; HIV-1; Humans; Incidence; Insecticides; Malaria; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

The aim of this study was to examine the clinical importance and causes of a positive result in the direct antiglobulin test (DAT) in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied haematological parameters in outpatient samples, and also analysed the impact of highly active anti-retroviral therapy (HAART) on the DAT results.. Haematological parameters, clinical stages, chemo-antibiotic treatments and HAART treatment were studied to determine any relationships with DAT results in 115 consecutive HIV(+) patients.. Significantly lower haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim-suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant association with DAT positivity. Patients receiving HAART were less likely to have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl) than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The surface exploratory analysis indicated the distribution of the positive DATs in relationship with the CD4(+) count and Hb levels.. Significantly lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The presence of red blood cell autoantibodies may be associated with anaemia in HIV disease in the absence of overt haemolysis.

Topics: Anemia; Antiretroviral Therapy, Highly Active; Coombs Test; Female; Hemoglobins; Hepatitis B; HIV Infections; Humans; Male; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In the Joint United Nations Programme on HIV/AIDS (UNAIDS) approach to HIV and AIDS estimates, estimates of adult prevalence produced by the Estimation and Projection Package (EPP) or the Workbook are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV by age and sex, new infections, AIDS deaths, AIDS orphans, treatment needs, and the impact of treatment on survival.. The UNAIDS Reference Group on Estimates, Models and Projections recommends updates to the methodology and assumptions based on the latest research findings and international policy and programme guidelines. The latest update to Spectrum has been used in the 2005 round of global estimates.. Several new features have been added to Spectrum in the past two years. New patterns of the age distribution of prevalence over time are based on the latest survey data. A more detailed treatment of mother to child transmission of HIV is now based on information about current breastfeeding practices, treatment options offered to prevent mother to child transmission (PMTCT), infant feeding options, and the percentage or number of pregnant women accessing PMTCT services. A new section on child survival includes the effects of cotrimoxazole and ART on child survival. Projections can now be calibrated with national survey data. A new set of outputs is provided for all adults over the age of 15 in addition to the traditional 15-49 age group. New outputs are now available to show plausibility bounds and regional estimates for key indicators.. The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners.

Topics: Adolescent; Adult; Age Distribution; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Child; Disease Outbreaks; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Male; Middle Aged; Models, Statistical; Needs Assessment; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Sex Distribution; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States.. During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews.. The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use.. High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

Topics: Adolescent; Adult; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Community-Acquired Infections; Comorbidity; Disease Progression; Female; HIV Infections; Humans; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Risk-Taking; Smoking; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Viral Load

Pediatric adherence to daily drug regimens has not been widely assessed in Africa where majority of HIV infected children live. Using in-depth interviews of 42 HIV-infected children taking ART and/or cotrimoxazole prophylaxis, and 42 primary caregivers, at a comprehensive HIV/AIDS clinic in Uganda, we evaluated their adherence experiences for purposes of program improvement. Daily drug regimens provided by the pediatric clinic included cotrimoxazole prophylaxis as well as ART and cotrimoxazole combined. Complete disclosure of HIV status by caregivers to children and strong parental relationships were related to good adherence. Structural factors including poverty and stigma were barriers to adherence even for children who had had complete disclosure and a supportive relationship with a parent. To ensure adherence to life-extending medications, our findings underscore the need for providers to support caregivers to disclose, provide on-going support and maintain open communication with HIV-infected children taking cotrimoxazole prophylaxis and ART.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Caregivers; Child; Child, Preschool; Drug Therapy, Combination; HIV Infections; HIV Seropositivity; Humans; Interviews as Topic; Patient Compliance; Trimethoprim, Sulfamethoxazole Drug Combination; Truth Disclosure; Uganda

Cotrimoxazole is recommended for prevention of opportunistic infections in symptomatic HIV patients in sub-Saharan Africa.. We examined the feasibility and effectiveness of daily cotrimoxazole prophylaxis in a well-established cohort of HIV-infected adults attending clinics in Entebbe, Uganda. We compared mortality and morbidity rates for 12 months before and after the introduction of cotrimoxazole.. Between August 2000 and February 2002, 94% of cohort members were enrolled onto cotrimoxazole prophylaxis. Revisits were scheduled every 4 weeks to replenish pills; patients attended 61% of revisits. The main reasons for nonenrollment and defaulting were lack of transport, being away from home, and sickness. Drug-related adverse events, mainly itching and rash, were seen in 4% of participants. Although bacterial resistance rate to cotrimoxazole was high, the adjusted mortality incidence rate ratio was significantly reduced after the introduction of cotrimoxazole (0.76; 95% confidence interval, 0.60-0.96; P = 0.020). Overall febrile events and morbidity rates were unchanged after the introduction of cotrimoxazole, but the incidence of malaria was reduced (incidence rate ratio, 0.31; 95% confidence interval, 0.13-0.72).. Cotrimoxazole prophylaxis can be introduced into routine HIV clinic activities and is associated with a reduction in overall mortality and malaria morbidity, even in an area with high bacterial resistance. These results reinforce the need for large-scale provision of cotrimoxazole prophylaxis for all HIV-positive patients in developing countries.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Feasibility Studies; HIV Infections; Humans; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Topics: Africa South of the Sahara; Antimalarials; Chemoprevention; Disease Outbreaks; Drug Combinations; Female; HIV Infections; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prevalence; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: HIV Infections; Humans; Malaria, Falciparum; Pyrimethamine; Sulfadoxine; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.

Topics: Animals; Antimalarials; Cohort Studies; Drug Combinations; Drug Resistance; Family; HIV Infections; Humans; Malaria, Falciparum; Mutation; Plasmodium falciparum; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed.. We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Côte d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy.. Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S. dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen.. A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources.

Topics: Adult; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Cohort Studies; Computer Simulation; Cost-Benefit Analysis; Cote d'Ivoire; Direct Service Costs; Disease Progression; Drug Costs; Health Resources; HIV; HIV Infections; Humans; Life Expectancy; Models, Biological; Monte Carlo Method; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

The threat for opportunistic diseases in HIV-infected adults in sub-Saharan Africa is characterized by a higher frequency of tuberculosis and invasive bacterial diseases than in Europe and by the presence of malaria. Since these three infections may occur early after the onset of immuno-deficiency, HIV-infected patients with less than 200 CD4/mm3 are more likely to develop an infectious episode with severe morbidity in sub-Saharan Africa than in Europe. For this reason the WHO now recommends starting cotrimoxazole prophylaxis at 350 and even 500 CD4/mml in sub-Saharan Africa. The question of whether antiretroviral treatment should also be initiated "earlier" in sub-Saharan Africa than in Europe has also been raised.

Topics: Africa South of the Sahara; Anti-Infective Agents; Antitubercular Agents; Bacterial Infections; HIV Infections; Humans; Malaria; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; Infant Mortality; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV) infected children are at risk of a range of lung diseases related to HIV infection, including tuberculosis (TB). As in non-HIV-infected children, the presence of three or more of the following four features strongly suggests the diagnosis of TB: 1) chronic symptoms suggestive of TB; 2) physical changes highly suggestive of TB; 3) a positive tuberculin skin test; 4) a chest radiograph suggestive of TB. Every effort must be made to expedite the process of making the diagnosis, as TB may be rapidly progressive in HIV-infected children. As many children who present with chronic symptoms suggestive of TB may not have been tested for HIV infection, in high HIV prevalence settings (and in all settings where HIV is suspected in a child) children and their families should be offered HIV counselling and testing as part of a full TB work-up. Most current international guidelines recommend that TB in HIV-infected children, as in non-HIV-infected children, should be treated with a 6-month regimen containing rifampicin throughout. All HIV-infected children with advanced immunosuppression, including many with TB, should receive cotrimoxazole prophylaxis. Although the optimal timing for the initiation of antiretroviral treatment (ART) during TB treatment is not known, the decision to initiate ART should take into consideration the degree of immune suppression and the child's progress during TB treatment.

Topics: Anti-Infective Agents; Antibiotics, Antitubercular; Antiviral Agents; Child; Drug Therapy, Combination; HIV Infections; Humans; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

OBJECTIVE We sought to determine the etiologies, manifestations, and risk factors for persistent (> or =7 days) diarrhea in human immunodeficiency virus type 1 (HIV-1)-infected persons in Peru.. The present study is a case-control study of 147 HIV-1-infected case subjects with persistent diarrhea and 147 HIV-1-infected control subjects without diarrhea.. We obtained clinical, demographic, and exposure data, CD4 lymphocyte counts, and stool samples for detection of enteric parasitic and bacterial pathogens and rotavirus.. One or more enteric pathogen was identified in 55% of case subjects and 21% of control subjects (odds ratio adjusted for CD4 lymphocyte count, 3.8; 95% confidence interval, 2.2-6.5). The median CD4 lymphocyte count was highest with pathogen-free diarrhea and lowest with Cryptosporidium infection. Cryptosporidium species (the most frequent pathogen), Giardia lamblia, Aeromonas species, Campylobacter species, and rotavirus were all significantly associated with diarrhea. Bacterial pathogens were significantly associated with G. lamblia and rotavirus infection. Of the bacterial pathogens (Aeromonas, Campylobacter, Salmonella, and Vibrio species and enterotoxigenic Escherichia coli), only 24% were susceptible to cotrimoxazole, whereas 90% were susceptible to ciprofloxacin. In no case did the sensitivity or positive predictive value of specific clinical and laboratory findings for curable enteric infections exceed 50%.. Several enteric pathogens were associated with diarrhea in HIV-1-infected case subjects in Peru, especially among those who were heterosexual. Clinical findings were poor predictors of detectable microbial etiology. The guidelines for initial management of chronic diarrhea with sulfamethoxazole-trimethoprim in HIV-1-infected persons require revision, at least in settings where prophylaxis with this agent is common.

Topics: Adult; Aeromonas; Animals; Anti-Infective Agents; Bacterial Infections; Campylobacter; Case-Control Studies; CD4 Lymphocyte Count; Ciprofloxacin; Cryptosporidium; Diarrhea; Escherichia coli; Feces; Female; Giardia lamblia; HIV Infections; Humans; Male; Middle Aged; Peru; Protozoan Infections; Risk Factors; Rotavirus; Rotavirus Infections; Salmonella; Trimethoprim, Sulfamethoxazole Drug Combination; Vibrio

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Child; Clinical Trials as Topic; HIV Infections; Humans; Practice Guidelines as Topic; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Adults with dual tuberculosis (TB) and HIV infection have a poor outcome. Studies in West Africa suggest that cotrimoxazole prophylaxis may reduce this mortality.. To evaluate the effectiveness of cotrimoxazole in reducing mortality in adults with active TB, irrespective of HIV status, in a high prevalence setting.. Cohort study using historical controls.. Adults treated for TB between 1998 and 2000 were traced and vital status at 6 months ascertained (2004: control group). All adults starting treatment for TB between June 2001 and June 2002 were offered cotrimoxazole prophylaxis 960 mg once daily for 6 months during TB treatment irrespective of HIV status (1321: intervention group). Mortality, adverse reactions and adherence were compared between intervention and control groups.. HIV seroprevalence in patients with TB at the start of the intervention was estimated to be 78%. Mortality at 6 months was 29% lower in the group given cotrimoxazole than in the control group. The number needed to treat to prevent one death during the period of TB treatment was 24. The benefit was seen across all types of TB but was only evident in new patients; patients being retreated had similar outcomes in both groups. Adverse events were infrequent and minor, with only two participants having treatment stopped for this reason.. Cotrimoxazole prophylaxis for all adults with TB, irrespective of HIV status, in an area of high HIV seroprevalence may be a feasible, safe and effective way to reduce mortality for the duration of treatment.

Topics: Adult; Anti-Infective Agents; Cohort Studies; Female; HIV Infections; Humans; Male; Patient Compliance; Prevalence; Rural Health; South Africa; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

From 1996 to 1998, a phase III, placebo-controlled, therapeutic trial was conducted in Abidjan, Ivory Coast, to assess the efficacy of cotrimoxazole prophylaxis in reducing severe morbidity in adults at early stages of human immunodeficiency virus infection. The authors used the real data from this trial to simulate three Bayesian interim analyses. Three prior distributions were considered: a noninformative one, a skeptical one, and one based on external information. The posterior distribution was calculated by using directed acyclic graphs and Gibbs sampling. This Bayesian approach showed different results according to the prior distribution chosen. Although use of the noninformative prior would have led to stopping the trial at the same time that the frequentist approach would have, the skeptical prior would have led to continuing it, and the prior based on external data would have led to stopping it 1 year earlier.

Topics: Anti-Infective Agents; Bayes Theorem; Clinical Trials, Phase III as Topic; Cote d'Ivoire; Endpoint Determination; HIV Infections; Humans; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; HIV; HIV Infections; Humans; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Topics: Adult; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Gingivitis; Gingivoplasty; Heroin Dependence; HIV Infections; Humans; Mandible; Methadone; Necrosis; Oral Ulcer; Pain; Stomatitis; Substance Abuse, Intravenous; Tooth Extraction; Tooth Loss; Treatment Refusal; Trimethoprim, Sulfamethoxazole Drug Combination

To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea.. A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status.. Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis.. Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea.. In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10).. This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Breast Feeding; Diarrhea, Infantile; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Risk Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin A

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Blood Sedimentation; Female; Fluconazole; Foot Dermatoses; Hand Dermatoses; Hepatomegaly; Herpes Zoster; HIV Infections; Humans; Hypergammaglobulinemia; Immunocompromised Host; Onychomycosis; Tinea; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Child, Preschool; Female; HIV Infections; Humans; Male; Mucocutaneous Lymph Node Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Currently, 95% of the 40 million persons with HIV live in low and middle income countries; 27 million in sub-Saharan Africa. HIV/AIDS is a leading cause of death in the region, yet access to care and treatment considered standard-of-care in the industrialized world is extremely limited. There is a need for standardized, evidence-based recommendations on preventive measures. We developed a list of potential interventions based, when possible, on documented efficacy in reducing morbidity or mortality among persons with HIV in Africa. We considered the accessibility, affordability, and potential for implementation using existing health care infrastructure. Potential components included cotrimoxazole prophylaxis, safe drinking water, isoniazid prophylaxis, insecticide-treated bed nets, micronutrients, and provision of HIV counseling and testing and condoms to family members of persons with HIV. There are several additional interventions for which further evaluation would be useful before inclusion in a standard package of care, including acyclovir prophylaxis, food supplementation, hand washing, and fluconazole prophylaxis. The provision of a basic care package could be an important step toward reducing health care disparities and gaining more control of the global HIV/AIDS epidemic.

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Bedding and Linens; Condoms; Counseling; Evidence-Based Medicine; Family Health; Health Services Accessibility; HIV Infections; Humans; Insecticides; Isoniazid; Micronutrients; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin A; Water Microbiology; Water Supply

Topics: Anti-Infective Agents; Anti-Retroviral Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Dapsone; Female; HIV Infections; Humans; India; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Topics: Bacteria; Bacterial Infections; Cambodia; Child; Colony Count, Microbial; Drug Combinations; Drug Resistance, Bacterial; Drug Resistance, Fungal; Drug Therapy, Combination; HIV Infections; Humans; Kenya; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

This study shows the long term safety of discontinuing secondary prophylaxis for Pneumocystis pneumonia in 5 human immunodeficiency virus-infected children who had recovered from a confirmed episode of Pneumocystis pneumonia, had <15% of CD4 cells at the time of starting highly active antiretroviral therapy and whose CD4 cell counts increased to >15% for >or=3 months during highly active antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Drug Administration Schedule; HIV Infections; HIV-1; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to assess the factors implicated in an increased or decreased risk of pneumonia, with particular attention to the response to highly active antiretroviral therapy (HAART) and the effect of the polysaccharide 23-valent pneumococcal vaccination in 300 human immunodeficiency virus (HIV)-infected adults followed-up for a median of 35.6 months. Pneumococcal pneumonia occurred in 12 patients and all bacterial pneumonia (pneumonia caused by Streptococcus pneumoniae or other bacteria, as well as those with negative cultures but presumably bacterial in origin) in 40 patients. In the univariate analysis, immunodepressed patients (defined as those with less than 200 CD4+ T cell/microl), those without immunological response to HAART (defined as an increase of 25% of CD4+ T lymphocyte count), patients with previous admissions to hospital and those with cotrimoxazole or Mycobacterium avium intracellulare prophylaxis showed a higher incidence of both pneumococcal and all bacterial pneumonia. Multivariate analysis demonstrated that the presence of pneumococcal pneumonia was associated with a CD4+ lymphocyte count at the time of HIV diagnosis <200 cells/microl. The multivariate model that was more valid for prediction of all bacterial pneumonia included a CD4+ T cell count <200 cells/microl and absence of immunological response to HAART. Only in patients with a baseline CD4+ T cell count lower than 200/microl and immunological response to HAART, a near significant lower incidence of all bacterial pneumonia was observed after vaccination. Thus, these results do not support an important additional protective effect of 23-valent pneumococcal vaccine in HIV-patients with immunological response to HAART.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Immunity; Incidence; Male; Mycobacterium avium-intracellulare Infection; Pneumococcal Vaccines; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; HIV Infections; HIV-1; Humans; Male; Nocardia Infections; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Antiretroviral Therapy, Highly Active; Comorbidity; Drug Resistance, Multiple, Bacterial; Female; HIV; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Streptococcus pneumoniae; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; HIV Infections; Humans; Male; Methemoglobinemia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Drug Resistance, Microbial; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; South Africa; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Fifteen hospitals in Malawi that offer voluntary counselling and testing (VCT) for the human immunodeficiency virus (HIV) for tuberculosis (TB) patients and cotrimoxazole (CTX) for patients found to be HIV-positive.. 1) To describe the process of developing a national TB-HIV plan, conducting a country-wide situational assessment, and producing national guidelines on VCT and CTX for TB patients, and 2) to assess the implementation of VCT and CTX for TB patients registered between July and September 2003.. A descriptive study.. The 3-year HIV-TB plan was finalised in 2002. Between January and March 2003, an assessment was carried out of HIV/AIDS and joint HIV-TB services in Malawi and a decision made to support 15 hospitals in implementing VCT and CTX for TB patients. Between April and June 2003, national guidelines on VCT and CTX were developed through a consultative process, and treatment units were prepared for implementation. Between July and September 2003, 2397 TB patients were registered, and 1404 (59%) accepted VCT; 956 (68%) were HIV-positive, of whom 927 (97%) started CTX. Deficiencies in the registration process and in patient understanding about VCT and CTX were identified.. The results show that it is feasible to routinely implement VCT and CTX for TB patients.

Topics: AIDS Serodiagnosis; Anti-Infective Agents; Antitubercular Agents; Counseling; Drug Therapy, Combination; HIV Infections; Humans; Malawi; National Health Programs; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Voluntary Programs

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Female; Hepatitis C, Chronic; HIV Infections; Humans; Lamivudine; Middle Aged; Nelfinavir; Reverse Transcriptase Inhibitors; Sweet Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

To reduce the number of daily pills for improving adherence to antiretrovirals, 17 protease inhibitor-treated patients receiving toxoplasmic encephalitis (TE) standard maintenance therapy were instead given cotrimoxazole 960 mg twice daily. After a median follow-up of 31 months, one relapsed after three months, TE relapse incidence = 2.1 cases per 100 patient-years (95% confidence interval, 0.05-11.3). This strategy could be useful for patients awaiting immune reconstitution which allows the interruption of TE maintenance therapy.

Topics: Animals; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; Follow-Up Studies; HIV Infections; Humans; Male; Recurrence; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported.. This study investigated the prevalence of DHPS mutations in P. jiroveci isolates from South African HIV-infected children with PCP by amplifying DNA using 2 different polymerase chain reactions.. P. jiroveci DNA from 30 respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a homogenous population with single DHPS mutations, 1 contained a homogenous population with 2 DHPS mutations, and the fourth contained a heterogenous population of organisms with both wild-type and single-mutant DHPS genotypes. Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis; this patient was infected with wild-type P. jiroveci. The mortality rate (overall, 20 [66.7%] of 30 children) was not significantly different between children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those infected with mutant strains (3 [75%] of 4; P=.8).. DHPS mutations are uncommon in P. jiroveci isolates from South Africa. However, increasing use of TMP-SMZ prophylaxis may result in widespread development of mutations.

Topics: AIDS-Related Opportunistic Infections; Dihydropteroate Synthase; HIV Infections; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the effect of orally administered trimethoprim-sulfamethoxazole (TMP-SMZ) on the prevalence, species distribution, and resistance of the conjunctival bacterial flora in adults with human immunodeficiency virus (HIV) infection.. Cross-sectional study, with clinical and experimental laboratory investigation.. Samples from the inferior conjunctival fornix were collected and submitted for culture to evaluate aerobic flora.. Sixty samples were collected. Negative cultures were found in 17 (56.7%) eyes of the TMP-SMZ group and in 10 (33%) of the control group (P = .036). All Staphylococcus species isolates in the TMP-SMZ group were resistant to the drug, whereas 50% of the control group presented this finding (P = .025). In the study group, all bacteria were resistant to TMP-SMZ, compared with only 47% of the microorganisms in the control group.. Orally administered TMP-SMZ in patients with HIV infection seems to exert a selection pressure in the microorganisms present on the conjunctiva.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Conjunctiva; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Emergence of P. jirovecii drug resistance has been suggested by the association between failure of prophylaxis with sulfa drugs and mutations in DHPS. However, data on the occurrence of mutations in DHFR, the target of trimethoprim and pyrimethamine, are scarce. We examined polymorphisms in P. jirovecii DHFR from 33 patients diagnosed with P. jirovecii pneumonia who were receiving prophylaxis with a DHFR inhibitor (n = 15), prophylaxis without a DHFR inhibitor (n = 11), or no prophylaxis (n = 7). Compared to the wild-type sequence present in GenBank, 19 DHFR nucleotide substitution sites were found in 18 patients with 3 synonymous and 16 nonsynonymous mutations. Of 16 amino acid changes, 6 were located in positions conserved among distant organisms, and five of these six positions are probably involved in the putative active sites of the enzyme. Patients with failure of prophylaxis, including a DHFR inhibitor, were more likely to harbor nonsynonymous DHFR mutations than those who did not receive such prophylaxis (9 of 15 patients versus 2 of 18; P = 0.008). Analysis of the rate of nonsynonymous versus synonymous mutations was consistent with selection of amino acid substitutions in patients with failure of prophylaxis including a DHFR inhibitor. The results suggest that P. jirovecii populations may evolve under selective pressure from DHFR inhibitors, in particular pyrimethamine, and that DHFR mutations may contribute to P. jirovecii drug resistance.

Topics: Adult; Amino Acid Sequence; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cloning, Molecular; DNA, Fungal; Drug Resistance, Fungal; Evolution, Molecular; Female; Folic Acid Antagonists; HIV Infections; Humans; Male; Middle Aged; Molecular Sequence Data; Mutation; Plasmids; Pneumocystis; Pneumocystis Infections; Pyrimethamine; Reverse Transcriptase Polymerase Chain Reaction; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination

Among children infected with human immunodeficiency virus (HIV), respiratory diseases are a frequent cause of morbidity and mortality. This review describes respiratory manifestations of paediatric HIV infection before and after the beginning of HAART in Abidjan, Ivory Coast. In an observational cohort, HIV infected children had quarterly clinical visits and a day-clinic available all week for ill children. CD4 and viral load were measured at baseline and every 6 months thereafter. All children with a CD4 percentage below 25% were prescribed daily cotrimoxazole prophylaxis. Ninety-eight children (of a total of 282) were recruited before HAART and treated during the follow-up, there were 56 boys and 42 girls, with a mean age of 6.2 years at inclusion. The mean percentage of CD4 before HAART was 8.7%. Twelve children had a history of pulmonary tuberculosis and five were on antituberculosis treatment at inclusion. Fifty-one per cent presented with abnormalities on chest X-ray at inclusion. Before initiation of HAART, respiratory manifestations represented 32.4% of morbidity events and the incidence for 100 child/months was 9.29 for URTI, 15.2 for bronchitis, 6.07 for LRTI, 0.71 for tuberculosis and 0.36 for Pneumocystis carinii. After the initiation of HAART, respiratory manifestations represented 40.9% of all morbidity events and the incidence for 100 child/months was 5.35 for URTI, 9.48 for bronchitis, 2.17 for LRTI and 0.16 for tuberculosis. During HAART treatment, the incidence of respiratory infections decreased dramatically compared to before the antiretroviral treatment. However, respiratory events still represented 40% of all events occurring following the start of HAART therapy.

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Child, Preschool; Cote d'Ivoire; Female; HIV Infections; Humans; Male; Respiratory Tract Diseases; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Arthritis, Infectious; Drug Therapy, Combination; Hepatitis C, Chronic; HIV Infections; Humans; Knee Joint; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Pneumocystis carinii; Pneumonia, Pneumocystis; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Osteoarticular

WHO/UNAIDS recommended that cotrimoxazole should be prescribed in Africa in HIV-infected adults with CD4 cell counts < 500 x 10 /l, while closely monitoring bacterial diseases in as many settings as possible.. Prospective cohort study, describing bacterial morbidity in adults receiving cotrimoxazole prophylaxis (960 mg daily) between April 1996 and June 2000 in Abidjan, Côte d'Ivoire.. Four-hundred and forty-eight adults (median baseline CD4 cell count 251 x 10 /l) were followed for a median time of 26 months. The rates of overall bacterial diseases and of serious bacterial diseases with hospital admission were 36.8/100 person-years (PY) and 11.3/100 PY, respectively. Bacterial diseases were the first causes of hospital admissions, followed by non-specific enteritis (10.2/100 PY), acute unexplained fever (8.4/100 PY), and tuberculosis (3.6/100 PY). Among serious bacterial diseases, the most frequent were enteritis (3.0/100 PY), invasive urogenital infections (2.5/100 PY), pneumonia (2.3/100 PY), bacteraemia with no focus (2.0/100 PY), upper respiratory tract infections (1.6/100 PY) and cutaneous infections (0.6/100 PY). Compared with patients with baseline CD4+ cell counts >or= 200 x 10 /l, other patients had an adjusted hazard ratio of serious bacterial diseases of 3.05 (95% confidence interval, 2.00-4.67; < 0.001). Seventy-five bacterial strains were isolated during serious episodes including 29 non-, 14, 12 spp, and 12.. Though with a medium-term rate half that of the short-term rate estimated under placebo before 1998 (26.1/100 PY), serious bacterial morbidity remains the first cause of hospital admission in adults receiving cotrimoxazole in this setting.

Topics: Adult; Anti-Infective Agents; Bacterial Infections; CD4 Lymphocyte Count; Cote d'Ivoire; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Incidence; Male; Morbidity; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001-0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004-0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87-20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.

Topics: Adult; Airway Obstruction; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Chemoprevention; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Infant Welfare; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal Welfare; Mother-Child Relations; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Protease Inhibitors; Respiratory Sounds; Reverse Transcriptase Inhibitors; Risk Factors; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi.. 'Before' and 'after' cohort study using historical controls.. Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group).. A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5.. This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemotherapy, Adjuvant; Child; Child, Preschool; Cohort Studies; Counseling; Feasibility Studies; Female; Follow-Up Studies; HIV Infections; HIV Seropositivity; Humans; Infant; Malawi; Male; Middle Aged; Patient Compliance; Proportional Hazards Models; Rural Health; Self Administration; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Voluntary Programs

A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi in order to 1) verify the acceptability of voluntary counselling and testing for human immunodeficiency virus (HIV) infection; 2) describe sexual behaviour and condom use; and 3) identify socio-demographic and behavioural risk factors associated with 'no condom use'.. Cross-sectional study.. Consecutive patients diagnosed with TB between January and December 2000 were offered voluntary counselling and HIV testing (VCT) and were subsequently interviewed.. There were 1,049 new TB patients enrolled in the study. Of these, 1,007 (96%) were pre-test counselled, 955 (91%) underwent HIV testing and 912 (87%) were post-test counselled; 43 (4%) patients refused HIV testing. The overall HIV infection rate was 77%. Of all HIV-positive TB patients, 691 (94%) were put on cotrimoxazole. There were 479 (49%) TB patients who reported sexual encounters, of whom only 6% always used condoms. Unprotected sex was associated with having TB symptoms for over 1 month, having had less than 8 years of school education, being single, divorced or widowed or having sex with the same partner.. Offering VCT to TB patients in this setting has a high acceptance rate and provides an opportunity to strengthen and integrate TB and HIV programmes.

Topics: Adult; Anti-Infective Agents; Comorbidity; Condoms; Counseling; Cross-Sectional Studies; Female; HIV Infections; Humans; Malawi; Male; Risk Factors; Rural Population; Sexual Behavior; Socioeconomic Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

1. to assess the impact of highly active antiretroviral therapy (HAART) on the occurrence of bacteraemia in HIV-infected patients and their clinical and microbiological characteristics. 2. to identify risk factors for bacteraemia in this setting.. The files of all HIV-infected patients hospitalized for an episode of bacteraemia in a 28-bed infectious diseases unit between January 1995 and December 1998 were reviewed. Cases occurring during HAART were compared to cases occurring in patients not receiving HAART. Furthermore, in a case-control study, patients with bacteraemia occurring during HAART were compared with other patients receiving HAART.. There were 74 episodes of bacteraemia in patients not receiving HAART and 31 episodes in patients receiving HAART. The occurrence of bacteraemia fell from 10.5/100 hospitalizations in 1995 to 5.5/100 in 1998 (P = 0.02 trend test). The occurence of P. aeruginosa bacteraemia fell sharply (9/398 vs 1/273, P = 0.05). A significant fall in catheter-related infections was observed between 1995 and 1998 (5.5% vs 1.8%). The two-thirds/one-third distribution of hospital-acquired and community-acquired infections remained stable throughout the period study. In patients receiving HAART, the case-control study showed by multivariate analysis, that a CD4 cell count of less than 100/ micro L [OR = 7.3 (1.9-49.7)], and the use of exogenous devices [OR = 13.3 (2.5-71)] were significantly associated with the risk of bacteraemia.. The introduction of HAART has been associated with a significant fall in the occurrence of bacteraemia. However, patients with a low CD4 cell count remain at risk of bacteraemia with similar microbiological and epidemiological characteristics than in the pre-HAART era.

Topics: Adult; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Bacteremia; Case-Control Studies; CD4 Lymphocyte Count; Chi-Square Distribution; Cross Infection; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Angioedema; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; HIV Infections; Humans; Infant; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To better understand the epidemiology of bacterial pathogens with particular public health importance in Taiwan, we determined the prevalence of nasal colonization with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a cohort of HIV-infected patients attending two hospital outpatient departments. All HIV-infected patients followed regularly between May and September 1999 were enrolled and cultures of the anterior nares were performed using a dry sponge swab. All confirmed S. aureus isolates underwent antimicrobial susceptibility testing using disk diffusion according to recommendations of the National Committee for Clinical Laboratory Standards. Of a total of 162 outpatients studied, 48 (30%) were found colonized with S. aureus including 39 (24%) colonized with MSSA and 9 (6%) colonized with MRSA. The only factor associated with MSSA colonization was receipt of trimethoprim-sulphamethoxazole which appeared protective (relative risk 0.4, 95% confidence interval [CI(95)] 0.2-0.78, P = 0.006). In contrast, ciprofloxacin use was an independent risk factor for MRSA colonization (conditional odds ratio [OR] 11.9, CI(95) 1.8-77.8, P = 0.010) along with a one-quartile reduction in CD(4) count (OR 3.9, CI(95) 1.1-14.3, P = 0.04). Although MRSA colonization was not associated with hospitalization within the previous three months, the multi-drug resistance pattern of MRSA isolates suggests strains were at some point acquired in the healthcare setting. Our study shows that the rate of S. aureus colonization in Taiwanese HIV-infected outpatients is 30%. Low CD4+ counts are most likely associated with other unmeasured risk factors for MRSA. Antimicrobial use may function alternatively as a protective or risk factor for colonization with S. aureus, depending upon the drugs involved and resistance encountered. Fluoroquinolone use may have an important role in the spread of MRSA from inpatient to outpatient settings.

Topics: Adult; Aged; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Ciprofloxacin; Cohort Studies; Female; HIV Infections; Humans; Male; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Nasal Cavity; Outpatient Clinics, Hospital; Penicillins; Prevalence; Risk Factors; Staphylococcus aureus; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the outcome of Legionnaires disease (LD) in patients with and without HIV infection.. Retrospective review of clinical charts.. Six hundred-bed university hospital.. We studied the clinical findings of 64 patients without HIV and 15 patients with HIV. Patients with a serologic diagnosis only were not included. Patients with previous immunosuppressive therapy or transplant recipients were excluded from the former group. In the HIV group, the mean CD4 cell count was 347.5/ microL, plasma viral load was undetectable in 50% of the patients, and only one patient (7%) was receiving cotrimoxazole as prophylaxis against Pneumocystis carinii at the time of pneumonia. No differences were observed in the two groups with respect to community or nosocomial acquisition, delay in the initiation of appropriate treatment, the use of macrolides or fluoroquinolones, and Fine score in cases of community-acquired LD.. Univariate analysis showed that time to apyrexia was longer, and respiratory symptoms, bilateral infiltrates in chest radiograph, hyponatremia, increase in aspartate aminotransferase and creatine phosphokinase (CK), and respiratory failure were more frequent in the HIV group. Mortality was greater in patients with HIV, achieving a statistically significant value of 20%; however, multivariate analysis only confirmed these differences with respect to the increase in CK.. LD has a more severe clinical presentation and worse evolution in patients with HIV.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Legionnaires' Disease; Male; Medical Records; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important.. To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence.. Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997.. Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%.. Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.

Topics: Adult; Antibiotics, Antitubercular; Botswana; Cross-Sectional Studies; Female; HIV Infections; HIV-1; Humans; Male; Mycobacterium tuberculosis; Pneumonia, Mycoplasma; Polymerase Chain Reaction; Prevalence; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Persons with acquired immunodeficiency syndrome (AIDS) have a higher incidence of invasive pneumococcal disease (IPD) than other adults, and many receive long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylactic therapy. We used 1998-1999 data from the Active Bacterial Core surveillance of the Emerging Infections Program Network to compare IPD infections between adults aged 18-64 years with human immunodeficiency virus (HIV) infection and other adults. Of 2346 patients with IPD, 416 (18%) had HIV or AIDS (HIV/AIDS). Certain serotypes (serotypes 6A, 6B, 9N, 9V, 18C, 19A, 19F, and 23F) were more common among patients with HIV/AIDS than in adults with no underlying disease (P<.05, vs. serotype 4), even when TMP-SMZ-nonsusceptible isolates were excluded. HIV/AIDS (adjusted odds ratio [aOR], 1.93; 95% confidence interval [CI], 1.44-2.59), immunocompromising conditions other than HIV/AIDS (aOR, 1.56; 95% CI, 1.12-2.18), and black race (aOR, 1.50; 95% CI, 1.20-1.88) were independent risk factors for infection with these serotypes. HIV/AIDS was not an independent risk factor for TMP-SMZ nonsusceptibility. Vulnerability to certain serotypes among adults with HIV/AIDS may have implications in prevention strategies.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Pneumococcal Infections; Population Surveillance; Risk Factors; Serotyping; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Atovaquone; Clinical Protocols; Dapsone; Drug Therapy, Combination; HIV Infections; Hospital Administration; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

Isolates of Pneumocystis jiroveci from sulfa-exposed and nonexposed patients from London, United Kingdom, and Harare, Zimbabwe, were genotyped. At the dihydropteroate synthase (DHPS) locus, there was evidence of selection pressure from sulfa drug exposure, and reversal of DHPS genotype ratios occurred when selection pressure was absent or was removed.

Topics: Genotype; HIV Infections; HIV-1; Humans; London; Mycoses; Pneumocystis; Pneumocystis Infections; Reverse Transcriptase Polymerase Chain Reaction; RNA, Ribosomal; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom; Zimbabwe

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4-CD8 Ratio; Depression; Didanosine; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Infectious Mononucleosis; Male; Reverse Transcriptase Inhibitors; Ritonavir; Stavudine; Treatment Refusal; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Viremia; Zalcitabine; Zidovudine

Topics: Adult; Anti-Infective Agents; Ciprofloxacin; Gonorrhea; HIV Infections; Homosexuality, Male; Humans; Male; Rectal Diseases; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.

Topics: Adult; Anti-Infective Agents; Cell Survival; Drug Hypersensitivity; Drug Monitoring; Female; HIV Infections; Humans; In Vitro Techniques; Indicators and Reagents; Lymphocytes; Male; Middle Aged; Retrospective Studies; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Infections; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Thyolo, rural southern Malawi.. To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment.. A cross-sectional study.. A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier.. Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug.. In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Child; Cross-Sectional Studies; Female; HIV Infections; Humans; Malawi; Male; Middle Aged; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

We report the case of an HIV-infected woman, who presented with chronic and productive cough without sign of hypersensitivity (fever, cutaneous eruption, gastrointestinal disorders), while taking abacavir. All complementary exams being negative, the involvement of abacavir has been suspected. So the drug was stopped leading to a rapid disappearance of cough. It is the first report of chronic cough with abacavir apart of a context of hypersensitivity reaction.

Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Chronic Disease; Cough; Cyclopropanes; Dideoxynucleosides; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Middle Aged; Nelfinavir; Oxazines; Reverse Transcriptase Inhibitors; Rhinitis; Sputum; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Syphilis; Trimethoprim, Sulfamethoxazole Drug Combination

Mycoplasma contamination of the licensed anthrax vaccine administered to military personnel has been suggested as a possible cause of Persian Gulf illness. Vaccine samples tested by nonmilitary laboratories were negative for viable mycoplasma and mycoplasma DNA and did not support its survival. Mycoplasma contamination of anthrax vaccine should not be considered a possible cause of illness.

Topics: Adult; Anti-Bacterial Agents; Child; Diarrhea; Dysentery, Bacillary; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Prevalence; Salmonella Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

The impact of chronic prophylactic administration of trimethoprim-sulfamethoxazole (SXT) on the ecology and the antimicrobial susceptibilities of bloodstream pathogens in human immunodeficiency virus (HIV)-infected patients was studied using a retrospective chart review. Eighty-nine patients with advanced HIV infection developed 124 episodes of bacteremia with 156 pathogenic isolates. Staphylococcus aureus and Enterobacteriaceae tended to be less common among patients receiving SXT. Isolates from patients receiving SXT were likelier (75%) to be resistant to 20 microg of SXT/ml than those from patients not receiving SXT (33%) (P < 0.001).

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Chemoprevention; Enterobacteriaceae; Female; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse reactions to sulfonamides occur at a higher frequency in patients infected with the human immunodeficiency virus (HIV) than noninfected patients. Some studies have suggested that patients with the slow acetylator phenotype are predisposed to these reactions, whereas other studies suggest that the slow acetylator genotype is not a predisposing factor. To rationalize these seemingly contradictory observations, the authors determined the N-acetyltransferase 2 (NAT2) genotype and phenotype in patients with and without a history of hypersensitivity reactions to sulfonamides. HIV-infected patients with a history of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were enrolled, along with a group of AIDS patients with no history of hypersensitivity (delayed or immediate). NAT2 phenotype was determined in both groups using dapsone, while the genotype was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of 14 patients (57%) without such a history exhibited this same phenotype (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a history exhibited this genotype (ns). There were more instances of discordance between deduced and actual phenotype in the nonhypersensitive patients (n = 4) than in the hypersensitive patients (n = 1). The reported higher frequency of the slow acetylator phenotype among patients with a history of hypersensitivity to sulfonamides does not appear to be explained by metabolic changes that would cause discordance between acetylator genotype and phenotype.

Topics: Acetylation; Adult; Anti-Infective Agents; Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genotype; HIV Infections; Humans; Male; Middle Aged; Phenotype; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Bacterial Infections; CD4 Antigens; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Although prolactin (PRL) is now recognized as a cytokine and persistent immune activation is a common immunopathogenic feature of the human immunodeficiency virus infection (HIV), the circumstances associated with the onset of hyperprolactinemia during the course of this infection remain controversial. Given that PRL is able to exert not only endocrinologic effects but also immunologic influences, a study was conducted to investigate whether raised serum levels of PRL were more likely to prevail when HIV-infected patients developed concomitant infections. Serum PRL concentrations, as well as immunoglobulin isotypes, plasmatic viral burden, CD3+, CD4+, CD8+, CD19+, and natural killer (NK) cell counts were measured in 46 nonselected HIV-infected patients stratified on the basis of the presence or absence of clinically active concomitant infections. Serum PRL levels were significantly higher in patients presenting secondary infections as compared with the asymptomatic ones, with hyperprolactinemia being detected in 10/18 (55%) and 2/28 (7%) of these patient groups, respectively. Hyperprolactinemia was not related with viral burden, antiretroviral treatment, gender differences, or CD4+ cell counts. CD3+, CD4+, CD8+, and CD19+ cells were significantly lower in the group presenting active infections, whereas comparisons in NK cell counts, immunoglobulin levels and HIV viral burden revealed no differences between groups. These results provide evidence that hyperprolactinemia is more prevalent during the onset of secondary infections, which might have diagnostic and therapeutic consequences.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4-CD8 Ratio; Female; HIV Infections; Humans; Immunoglobulins; Indinavir; Lamivudine; Male; Prolactin; Sex Factors; T-Lymphocyte Subsets; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Zidovudine

Topics: Antimalarials; Comorbidity; HIV Infections; HIV-1; Humans; Immunocompromised Host; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Diagnosis, Differential; HIV Infections; Humans; Hypothyroidism; Male; Pneumonia, Pneumocystis; Thyroxine; Trimethoprim, Sulfamethoxazole Drug Combination

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Attitude of Health Personnel; Bayes Theorem; Clinical Trials as Topic; Dapsone; Ethics, Medical; HIV Infections; Humans; Naphthoquinones; Physicians; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Sample Size; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abnormalities, Drug-Induced; Anti-Infective Agents; Cleft Lip; Female; Folic Acid Antagonists; Heart Defects, Congenital; HIV Infections; Humans; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract

A rare sepsis-like hypersensitivity reaction has been observed in persons with human immunodeficiency virus (HIV) after exposure to trimethoprim-sulfamethoxazole. This reaction most commonly occurs on rechallenge with the drug and is manifested by a syndrome resembling bacterial sepsis. The mechanism of this unusual reaction remains unclear. We describe the first case in which this severe hypersensitivity reaction was the initial manifestation of HIV.

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Drug Hypersensitivity; HIV Infections; Humans; Male; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Pneumonia, Pneumocystis; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Immunocompromised Host; Lymphoma, Non-Hodgkin; Male; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMZ) is widely prescribed as prophylaxis for Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected persons. Its efficacy against other infections has not been thoroughly evaluated. To compare the risk for infectious diseases for persons who were prescribed TMP-SMZ with that for patients who were not prescribed TMP-SMZ, we examined data collected from the medical records of HIV-infected patients (January 1990 through September 1999) who were enrolled in the Adult and Adolescent Spectrum of HIV Disease Project. During intervals when patients had CD4(+) T lymphocyte counts of <200 cells/microL (19,081 persons; 22,801 person-years), prescription of TMP-SMZ was associated with significant protection from toxoplasmosis, salmonellosis, infection with Haemophilus species, invasive or any staphylococcal infection, and PCP, but not from Shigella, pneumococcal or nonpneumococcal Streptococcus, Klebsiella, or Pseudomonas species. We demonstrate that prescription of TMP-SMZ for PCP prophylaxis in persons with HIV infection is associated with significantly decreased risk for several infectious diseases. These findings may be of interest to HIV prevention programs in resource-poor countries.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Bacterial Infections; Female; HIV Infections; Humans; Male; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Drug Administration Schedule; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Developing Countries; Ethics, Medical; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Nevirapine; Patient Education as Topic; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Antitubercular Agents; Clinical Trials as Topic; Cote d'Ivoire; Drug Therapy, Combination; HIV Infections; Humans; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Alcohol Drinking; Candidiasis, Oral; CD4 Lymphocyte Count; Drug Therapy, Combination; HIV Infections; Humans; Lamivudine; Male; Pneumonia, Bacterial; Sexual Partners; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Zidovudine

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.

Topics: Adult; Community-Acquired Infections; Female; HIV Infections; Humans; Logistic Models; Male; Middle Aged; Pneumonia; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Hypersensitivity; Follow-Up Studies; HIV Infections; Humans; Immune Tolerance; Pneumocystis Infections; Therapeutic Equivalency; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Children with HIV infection are particularly susceptible to invasive pneumococcal disease, yet the effect of HIV infection and its medical management on colonization and resistance to antibiotics are poorly described. To provide a basis for medical practice, we determined the prevalence of nasopharyngeal colonization and antibiotic resistance of Streptococcus pneumoniae in children with HIV infection.. Cross-sectional prevalence sample of children attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal colonization with S. pneumoniae and antibiotic resistance to beta-lactams and trimethoprim-sulfamethoxazole (T/S). Subjects were matched by age and date of clinic visit.. The colonization rate with S. pneumoniae of HIV-infected and -indeterminate children was equal to that of controls (20% vs. 19%). HIV infection, CDC staging or receipt of oral antibiotic therapy did not affect colonization. Isolates from HIV-infected and -indeterminate children were less likely to be penicillin-resistant than those from controls (18% vs. 50%). There was no difference in pneumococcal resistance to T/S among isolates from subjects and controls, despite 72% T/S use in the HIV clinic.. Colonization with S. pneumoniae in HIV disease is no different from that of comparable children. The high incidence of pneumococcal disease and prophylaxis with T/S are not related to nasopharyngeal colonization. Antibiotic prophylaxis of HIV-infected children does not necessarily lead to increased resistance of S. pneumoniae.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Carrier State; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Drug Resistance, Microbial; Female; HIV Infections; Humans; Infant; Lactams; Male; Nasal Mucosa; Nasopharynx; Penicillins; Pneumococcal Infections; Prevalence; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (T/S) is an essential drug in patients with human immunodeficiency virus type-1 (HIV-1) infection to prevent opportunistic infections. About 40% to 60% of them develop skin rash which leads to discontinue the medication. A precise mechanism of the reaction is not known.. To make the patients more tolerable to the medication and to make clear whether or not the reaction is caused by serum sulfamethoxazole-specific IgE.. We established a 5-day protocol, in which T/S was administered orally as a granular form in increasing doses beginning with 0.005 g (it contains trimethoprim 0.4 mg and sulfamethoxazole 2 mg) and doubled every 12 hours until the therapeutic dose was achieved. We tried to desensitize T/S in 17 patients with HIV-1 infection who were previously intolerant to T/S and measured the specific IgE in sera.. Desensitization was successfully completed in 15 (88.2%) of the patients. In two patients who failed the desensitization, one was due to fever and the other was gastric irritation. During followup in a mean period of 16.6 months (range, 8 to 23 months) as of May, 1999, none has had Pneumocystis carinii pneumonia (PCP) while receiving T/S after desensitization. Sulfamethoxazole-specific IgE did not increase, indicating that it was not the major cause of skin rash due to T/S in our cases.. These preliminary results show that most patients who were thought to be intolerant to T/S and had no sulfamethoxazole-specific IgE can be safely desensitized and received the drug subsequently as an effective prophylaxis for PCP.

Topics: Administration, Oral; Adolescent; Adult; CD4-Positive T-Lymphocytes; Desensitization, Immunologic; Drug Tolerance; Female; HIV Infections; HIV-1; Humans; Immunoglobulin E; Lymphocyte Count; Male; Middle Aged; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

HIV positive women of reproductive age are increasingly treated with a combination of antiretroviral agents, with effects on the developing human fetus that are largely unknown. We report two cases of severe spinal malformations in the fetuses of women treated with combination antiretroviral therapy and co-trimoxazole.

Topics: Abnormalities, Drug-Induced; Adult; Anti-HIV Agents; Female; HIV Infections; Humans; Pregnancy; Pregnancy Complications, Infectious; Spine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Chemoprevention; HIV Infections; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous adverse drug reactions in HIV-positive patients with their wide spectrum of manifestations remain a diagnostic and therapeutic challenge. Skin diseases as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis belong to this group. The typical primary lesions are erythematous macules and papules, which rapidly extend to the entire body and may be accompanied by a extensive epidermal detachment. Diagnosis and immediate therapy is indispensable because of the possible fulminant course of the disease. We report a HIV-positive patient with a cutaneous adverse drug reaction showing predominantly hemorrhagic lesions.

Topics: AIDS-Related Opportunistic Infections; Diagnosis, Differential; Drug Eruptions; Drug Therapy, Combination; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity from trimethoprim/sulfamethoxazole (TMP/SMX) has been linked to a reactive nitroso intermediate from sulfamethoxazole metabolism, which may be altered in patients with human immunodeficiency virus (HIV) infection. The authors determined the clinical factors that are associated with TMP/SMX hypersensitivity in patients with HIV. In a case control study, 54 controls currently tolerating TMP/SMX prophylaxis were randomly matched by date of hypersensitivity reaction in case patients to 28 patients with a history of a rash consistent with erythema multiforme from TMP/SMX. Demographic data, coadministered medications, laboratory data, and histories of opportunistic infections were extracted on all patients. A highly significant association was observed between the number of opportunistic infections and the occurrence of TMP/SMX hypersensitivity (p < 0.001), despite comparability of CD4 counts between case patients and controls (p > 0.1). A tendency for protection from TMP/SMX hypersensitivity in blacks was also observed (p = 0.066). These observations suggest that the mechanisms by which HIV produces cellular immune dysfunction and alters drug detoxification may be linked.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

We sought to study asymptomatic pancreatic enzyme abnormalities in patients with human immunodeficiency virus (HIV) infection.. Serial serum amylase and lipase determinations were performed in ambulatory HIV-seropositive patients in whom pancreatitis was not suspected.. Eighty-six patients were enrolled in the study. Fifty-two patients (60%) were found to have abnormal amylase or lipase values on at least one determination. Only 12 (14% of all patients) had a more than twofold elevation of pancreatic enzymes. Seven patients had transient elevations of lipase within 3 months after the initiation of antiretroviral therapy. Independent factors associated with abnormal pancreatic enzymes were: positive serology for chronic hepatitis B or C, history of intravenous cotrimoxazole administration for the treatment of Pneumocystis carinii pneumonia, stage B of HIV disease, and HIV risk factors other than male homosexuality (mainly intravenous drug use). None of the patients developed clinical pancreatitis.. Asymptomatic mild to moderate elevations of amylase or lipase are common in HIV-positive patients, and are usually associated with positive serology for chronic hepatitis B or C, and medications, especially antiretrovirals and intravenous cotrimoxazole.

Topics: Adult; Aged; Amylases; Anti-Infective Agents; Female; Hepatitis, Viral, Human; HIV Infections; HIV Seropositivity; Homosexuality; Humans; Lipase; Male; Middle Aged; Risk Factors; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

To establish the safety and efficacy of desensitization to co-trimoxazole in hypersensitive HIV-infected subjects. To assess if delayed hypersensitivity (type IV) to co-trimoxazole predicts those unable to be desensitized.. desensitization to co-trimoxazole, comprising trimethoprim (T) 0.4 mg and sulphamethoxazole (S) 2 mg initially with doubling dose daily, full strength co-trimoxazole (T/S 160 mg/800 mg) at 10 days. Patch testing with 4.5% and 9% co-trimoxazole in yellow soft paraffin, CMI Multitest.. nineteen patients, 18 male and one female, were recruited and completed the desensitization regime. Of these 80%(15) achieved successful desensitization. Three of those who reacted did so within 18 days. All patients were successfully managed in an outpatient setting. There were no major adverse reactions. Of those reacting none gave a positive patch test to co-trimoxazole and all showed absent delayed type hypersensitivity reactions to recall antigens.. co-trimoxazole desensitization is a safe and efficacious procedure, with a success rate of 80% using the above regime. Patch testing with co-trimoxazole gives no useful information about those that reacted.

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Hypersensitivity, Delayed; Male; Outpatients; Patch Tests; Pneumonia, Pneumocystis; Predictive Value of Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; HIV Infections; Humans; Hydroxylamine; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Ethics, Medical; Fatal Outcome; Female; HIV Infections; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

HIV infection is common in young persons and its clinical picture, outcome and response to antiretroviral therapy is well known, but it is not the case in the elderly.. To evaluate the clinical characteristics and response to antiretroviral therapy of HIV elderly patients.. Retrospective study of 37 patients elder than 60 years. The control group comprised of 64 HIV positive patients with less than 60 years. None of them were drug abusers.. The mean age of patients was 65 years (range 60-79), 86% were males. The most frequent causes for HIV testing were: wasting (22%), P. carinii pneumonia (19%), tuberculosis (13%) and Kaposi sarcoma (10%), but in the control group voluntary testing was the most common reason (64%). The mean CD4 count at diagnosis was lower in the elderly group (233 cells/microL vs 323 cells/microL). During follow up, the most frequent complications for those with less than 200 CD4 cells were: oral candidiasis (44%), P. carinii pneumonia (27%), Kaposi sarcoma (22%) and esophageal candidiasis (22%), while in the young group P. carinii pneumonia (22%), Kaposi sarcoma (9%) and esophageal candidiasis (9%) were less frequent. 67% of the elderly received antiretroviral therapy. Zidovudine had to be discontinued due to anaemia in half of them. Survival at 6 and 12 months was significantly longer in treated patients compared to those who did not received antiretrovirals (100% vs 14% at 6 months, P < 0.001; and 54% vs 0% at 12 months, p = 0.03); and at 2 years it was almost similar to that of the young group (36% vs 52%, p = 0.38).. HIV infection in the elderly is generally diagnosed in an advance stage, but antiretroviral therapy prolongs survival. Zidovudine should be reserve as a second line drug because its frequent haematological toxicity.

Topics: Adult; Age Factors; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Data Interpretation, Statistical; Female; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Sex Factors; Software; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

A case-control study was carried out in Libreville, Gabon, to determine the incidence of salmonella infection in HIV patients and identify any special clinical, therapeutic, or prognostic features. The records of 3000 patients hospitalized in the Infectious Disease Department of the Jeanne Ebori Foundation between January 1990 and December 1994 were studied. The incidence of salmonella infection, serotype, clinical presentation, prognostic factors and therapeutic modalities were compared in 2759 HIV-positive patients and 441 HIV-negative patients. Salmonella infection was noted in a total of 208 patients (58 HIV-positive and 150 HIV-negative). The incidence of salmonella infection was 13 p. 100 (non-typhoid in 76 p. 100 of cases) in HIV-positive patients versus 5.4 p. 100 in HIV-negative patients. The predominant serotypes in HIV-positive patients were Salmonella typhimurium and Salmonella enteritidis which accounted 41 p. 100 and 26 p. 100 of the isolated strains. The only significantly difference in clinical presentation was a higher incidence of bacteremia (84 p. 100) and focal lesions (11.4 p. 100) in HIV-positive patients with low-grade salmonella infection. The duration of treatment was three weeks with cotrimoxazole and 10 days with fluoroquinolones and cephalosporines. The outcome in HIV-positive patients was recurrence-free cure in 40 p. 100, multiple relapses in 12 p. 100, and death in 24 p. 100. The remaining patients were lost from follow-up. This study demonstrates the gravity of low-grade salmonella infection in African HIV-positive patients. Early diagnosis is necessary to allow chemotherapy which can be effective despite immunodeficiency.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Cephalosporins; Female; Fluoroquinolones; Focal Infection; Follow-Up Studies; Gabon; HIV Infections; HIV Seronegativity; Humans; Incidence; Male; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Salmonella; Salmonella enteritidis; Salmonella Infections; Salmonella typhimurium; Serotyping; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Granuloma, Plasma Cell; HIV Infections; Humans; Liver Diseases; Magnetic Resonance Imaging; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; China; Drug Eruptions; Drug Hypersensitivity; Female; HIV Infections; Humans; Malaysia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Scotland; Trimethoprim, Sulfamethoxazole Drug Combination; White People

The aim of this retrospective study was to assess whether corticosteroid adjunctive therapy (CAT) could prevent death in immunocompromised patients with severe Pneumocystis carinii pneumonia (PCP) who do not have human immunodeficiency virus (HIV) infection, similarly to what has been demonstrated for HIV-infected patients. The charts of all non-HIV-infected patients who were admitted to two medical intensive care units between 1988 and 1996 because of severe PCP, defined by an arterial oxygen pressure (determined while the patient was breathing room air) of <70 mm Hg, and who were treated with trimethoprim-sulfamethoxazole were analyzed retrospectively. Thirty-one patients met the study criteria, of whom 23 received CAT (within 72 hours of antibiotic therapy) and eight did not receive CAT. The need for mechanical ventilation (10 [43%] of 23 vs. 4 [50%] of 8) and the mortality rate (9 [39%] of 23 vs. 4 [50%] of 8) were similar for the two groups. Although this small study does not have a statistical power high enough to rule out the possibility of a difference, the results suggest that CAT does not improve the survival of non-HIV-infected patients as has been described for HIV-infected patients with severe PCP.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Pneumonia, Pneumocystis; Reference Values; Retrospective Studies; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus (HIV)-infected patients, but little is known about the effects of this practice on the emergence of TMP-SMX-resistant bacteria. A serial cross-sectional study of resistance to TMP-SMX among all clinical isolates of Staphylococcus aureus and 7 genera of Enterobacteriaceae was performed at San Francisco General Hospital. Resistance among all isolates was <5.5% from 1979 to 1986 but then markedly increased, reaching 20.4% in 1995. This was most prominent in HIV-infected patients: resistance increased from 6.3% in 1988 to 53% in 1995. The largest increases in resistance were in Escherichia coli (24% in 1988 to 74% in 1995) and S. aureus (0% to 48%) obtained from HIV-infected patients. A rapid increase in the use of prophylactic TMP-SMX in HIV disease was also observed during this time in San Francisco and is likely responsible for the increase in TMP-SMX resistance.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Cross-Sectional Studies; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; HIV Infections; Humans; Microbial Sensitivity Tests; Pneumonia, Pneumocystis; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Male; Middle Aged; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate CD4 counts as a predictor of mortality in AIDS patients with respiratory failure due to Pneumocystis carinii pneumonia (PCP).. Retrospective chart review.. Urban university medical center.. Forty-eight patients admitted to the medical ICU from January 1993 to August 1996 with diagnosis of HIV/AIDS, PCP, CD4 count <200 cells per cubic millimeter, who required mechanical ventilation for respiratory failure.. Medical records were reviewed and age, CD4 count, lactate dehydrogenase, room air (RA) PaO2, coinfections, and day of admission to day of intubation (DOA-DOI) data were recorded.. All 48 patients (12 women and 36 men) were treated with corticosteroids and IV trimethoprim-sulfamethoxazole. Age ranged from 21 to 65 years; CD4, 1 to 180, RA PaO2, 27 to 93 mm Hg; and DOA-DOI, 0 to 20 days. Mortality varied significantly depending on CD4 counts: CD4 0 to 10 (100%); CD4 11 to 50 (88%); CD4 51 to 100 (50%); and CD4 >100 (25%). There were no significant difference in mortality between the groups with DOA-DOI <5 days (82%) vs >5 days (80%) or between the groups with PaO2 <60 mm Hg (85%) vs PaO2 >60 mm Hg (73%).. Even though overall mortality was 81%, the mortality rate was significantly different among the four groups. Most striking was the progressive increase in mortality as CD4 cells decreased from >100 (25% mortality) to <10 (100% mortality). Survivors had significantly higher CD4 cell counts than those who died. The CD4 cell count within 2 weeks of admission has significant prognostic value and may be helpful when counseling patients, families, and healthcare surrogates in end-of-life decision making.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Anti-Infective Agents; CD4 Lymphocyte Count; Comorbidity; Counseling; Decision Making; Evaluation Studies as Topic; Female; Florida; Forecasting; HIV Infections; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Oxygen; Patient Admission; Pneumonia, Pneumocystis; Prognosis; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic in a 5-year period were reviewed and compared against other patients attending the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration. 89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis (ANUG) and responded well to conventional treatment for ANUG. The cases were compared with 269 controls in logistic regression. Gingival ulceration was associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly due to a protective effect of co-trimoxazole medication. 5 patients with neutropenia had extensive ulceration without the microflora of ANUG. Histopathology, viral and bacterial culture revealed non-specific changes. The ulcers did not respond to the treatment regimen for ANUG but responded to treatment of their neutropenia. Gingival ulceration is not common in HIV infection. Most cases resemble severe ANUG. It is more frequent in younger people, those with oral candidiasis and without AIDS. Co-trimoxazole may be protective. A minority of cases with ulceration and associated neutropenia resembled the non-specific oral ulceration associated with HIV.

Topics: Adult; Analysis of Variance; Anti-Infective Agents; Candidiasis, Oral; Case-Control Studies; Chi-Square Distribution; Female; Gingivitis, Necrotizing Ulcerative; HIV Infections; Humans; Male; Neutropenia; Oral Ulcer; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

To examine the use of adjunctive corticosteroids in cases of severe Pneumocystis carinii pneumonia (PCP) in non-HIV-infected adult patients.. Retrospective review of medical records.. Tertiary care urban teaching hospital.. Review identified 31 consecutive histologically confirmed primary cases of adult non-HIV-related PCP. Complete records were available for 30 patients, including 20 male and 10 female patients with a mean age of 58.3+/-15 years (+/-SD). Underlying conditions included organ transplantation (n=13), long-term immunosuppressive therapy (n=9), and chemotherapy for malignancy (n=8). All patients had documented PO2 <65 mm Hg or arterial oxygen saturation <90% on room air.. Following the identification of P carinii, in addition to trimethoprim-sulfamethoxazole or pentamidine therapy, 16 patients received increased steroids (> or =60 mg prednisone daily equivalent; increased high-dose steroid group), whereas 14 patients were maintained on a regimen of low doses (< or =30 mg prednisone equivalent daily) or had steroid therapy tapered (low-dose steroid group).. The increased high-dose steroid group demonstrated a shorter required duration for mechanical ventilation (6.3+/-6 days vs 18.0+/-21 days; p=0.047), a shorter duration of ICU admission (8.5+/-7 days vs 15.8+/-8 days; p=0.025), and a shorter duration of supplemental oxygen use (10.0+/-4 vs 32.2+/-33; p=0.05). The hospital duration to discharge for the nine survivors in each group favored the use of corticosteroids (15.4+/-5 days vs 36.3+/-33 days; p=0.077). Similar rates were observed for intubation (75% vs 57%; p=0.442) and in-hospital mortality (44% vs 36%; p=0.722).. These preliminary data suggest that high-dose adjunctive corticosteroids may accelerate recovery in cases of severe adult non-HIV PCP.

Topics: Anti-Infective Agents; Antifungal Agents; Drug Therapy, Combination; Female; Glucocorticoids; HIV Infections; Humans; Intubation, Intratracheal; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Pneumonia, Pneumocystis; Saquinavir; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Diagnosis, Differential; Drug Eruptions; Drug Therapy, Combination; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Several clinical studies have suggested that anemia is an independent risk factor for dying in patients with HIV disease. We analyzed data from a large urban HIV clinical practice in Baltimore to assess the annual incidence of anemia, the risk of dying in patients who develop anemia, and the association between recombinant human erythropoietin use to treat anemia and subsequent survival. In 2348 patients observed between 1989 and 1996, 498 (21%) developed at least grade 1 anemia (hemoglobin <9.4 g/dl); 95 (4%) developed grade 4 anemia (hemoglobin <6.9 g/dl). Development of anemia was associated with decreased survival, independent of other prognostic factors. Use of erythropoietin was more likely in patients of nonminority race, those who did not inject drugs, those with a lower CD4 count or AIDS, and those being treated for cytomegalovirus disease (p < .05). Adjusting for these factors as well as severity of anemia, age, diagnosis of opportunistic disease, blood transfusion, and antiretroviral therapy in a time-dependent Cox proportional hazards analysis, erythropoietin use (n=91) was associated with a decreased hazard of dying (relative hazard [RH]=0.57; 95% confidence interval [CII, 0.40-0.81; p=.002). Although we cannot rule out a treatment selection bias, adjusting for available prognostic factors and factors potentially associated with a decision to use erythropoietin suggests that erythropoietin for treatment of anemia is associated with improved survival in HIV disease.

Topics: Adult; Anemia; Anti-HIV Agents; Anti-Infective Agents; Blood Transfusion; Erythropoietin; Female; Ganciclovir; Hemoglobins; HIV Infections; Humans; Incidence; Longitudinal Studies; Male; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To define the scope of taste and smell (chemosensory) complaints amongst HIV-infected persons in the study population; to evaluate the clinical factors associated with chemosensory complaints; and to determine the impact of chemosensory complaints on quality of life.. Cross-sectional survey.. Tertiary care university medical center clinic.. A total of 207 HIV-infected patients.. Chemosensory complaint score from taste and smell questionnaire and quality of life scores from the Medical Outcomes Study HIV Health Survey (MOS-HIV).. A total of 144 patients (70%) reported chemosensory complaints, 91 (44%) reported both taste and smell complaints, 47 (23%) reported only taste complaints, and six (3%) reported only smell complaints. Many patients complained that drugs interfered with their sense of taste, or that medications tasted bad. Higher chemosensory complaint scores were associated with a greater number of medications taken, tobacco use, and hay fever. Patients with chemosensory complaints had significantly lower scores in all domains of the MOS-HIV than those without complaints. Quality of life as measured by the MOS-HIV was lower in patients with chemosensory complaints even after controlling for number of AIDS diagnoses, number of medications, CD4 cell count, and HIV-1 viral load.. Chemosensory complaints were common in the patient population and were associated with a poor quality of life. Medications played an important role in chemosensory complaints. Measures to optimize taste and smell function may improve quality of life and medication adherence, and prevent complications such as inadequate oral intake, malnutrition, weight loss, and ultimately wasting.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Clarithromycin; Didanosine; Female; HIV Infections; Humans; Indinavir; Lamivudine; Male; Middle Aged; Quality of Life; Ritonavir; Smell; Surveys and Questionnaires; Taste; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis.. To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure.. The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure.. Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Topics: Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Anti-Infective Agents; Antifungal Agents; Atovaquone; Cohort Studies; Dapsone; Drug Therapy, Combination; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Morbidity; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; United States

To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up.. From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy.. Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months).. Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibodies, Protozoan; Antifungal Agents; Antiviral Agents; CD4 Lymphocyte Count; Chemoprevention; Coccidiostats; Databases as Topic; Female; Follow-Up Studies; France; HIV Infections; Humans; Incidence; Magnetic Resonance Imaging; Male; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Survival Rate; Time Factors; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To describe the epidemiologic, clinical, radiologic, laboratory and treatment characteristics of acute pneumonia and its association with mortality in HIV-infected children.. Data were collected during a trial of intravenous immunoglobulin (IVIG) for infection prophylaxis (1988 to 1991); CD4+ percentage was measured and HIV RNA was assessed on stored sera collected at baseline and every 3 months. Mortality was recorded during the trial and updated through 1996. All reported physician-diagnosed pneumonia episodes underwent blinded review for trial endpoint classification as acute (new radiologic findings and presence of clinical symptoms) or nonacute.. On blinded clinical trial endpoint review of all reported pneumonia episodes (n = 281), only 47% were classified as acute. One hundred thirty-one episodes of acute pneumonia were reported in 93 children (47 in 31 IVIG and 84 in 62 placebo patients, P < 0.01). The incidence of acute pneumonia was 24 episodes per 100 patient years. Findings associated with an acute bacterial process were uncommon (leukocytosis > or =15000/mm3 in 21% and fever > or =103 degrees F in 32% of episodes). Multiple acute episodes occurred in 34% of the children and were associated with increased risk of mortality in a univariate analysis (risk ratio, 2.1; 95% confidence interval, 1.3 to 3.4, P = 0.002), but in a multivariate model only baseline HIV RNA copy number and CD4+ percentage remained independently associated with mortality (relative risk, 2.0 and 1.4, respectively, P < 0.001).. Acute pneumonia was a common occurrence in HIV-infected children and was associated with long term mortality risk. Multiple episodes of acute pneumonia likely represent a marker of progressive disease and immunologic dysfunction rather than being causally associated with increased long term mortality.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bacterial Infections; CD4 Lymphocyte Count; Child; Child, Preschool; Clinical Trials as Topic; Female; HIV Infections; Humans; Immunoglobulins, Intravenous; Infant; Male; Pneumonia; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are very common in HIV-infected patients, leading to drug discontinuation. However, it is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia.. We sought to determine the safety and long-term efficacy of a 6-hour TMP-SMX-graded challenge in a group of hypersensitive HIV-infected patients.. Forty-four consecutive HIV-infected patients with documented TMP-SMX hypersensitivity were seen in our outpatient allergy department. They ingested 12 doses of increasing amounts of TMP-SMX at half-hour intervals. Thereafter, they took 80/400 mg TMP-SMX daily and were advised to "treat through" every nonbullous cutaneous adverse reaction.. All 44 patients tolerated the procedure without any adverse reactions during the day of challenge. Eleven of the 44 patients experienced mild hypersensitivity reactions on days 1 to 2 (8 patients) and 8 to 10 (3 patients), consisting mainly on a 1-day pruritic maculopapular eruption. Two patients stopped TMP-SMX at day 1, and 2 stopped it at days 10 and 15, giving an overall success rate at 1 month of 91% (40 of 44). Two were successfully rechallenged late. After a median follow-up of 10 months, 42 patients were taking TMP-SMX without any adverse reaction, giving an overall success rate of 95%.. A 6-hour graded challenge with cautious "treating through" of mild reactions enables more patients to take TMP-SMX and is safe and effective.

Topics: Administration, Oral; Adult; Drug Administration Schedule; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Indinavir use is associated with a spectrum of renal and urinary tract complications including nephrolithiasis, renal colic and pain without recognizable lithiasis, and a picture of crystalluria-dysuria. A frank nephropathy has not been recognized as part of the spectrum.. A retrospective analysis of 106 HIV-infected individuals receiving indinavir was performed with the purpose of identifying the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals receiving ritonavir or nelfinavir served as controls.. A sustained elevation of creatinine (>20%, into abnormal range) was identified in 20 (18.6%) subjects treated with indinavir but not with other protease inhibitors. Creatinine elevation was associated with treatment duration of more than 54 weeks [odds ratio (OR), 7.1; 95% confidence interval (CI), 1.8-27.7], low baseline body mass index < or = 20 kg/m2 (OR, 4.0; 95% CI, 1.0-16.6), and use of trimethoprim-sulphamethoxazole (TMP-SMX; OR, 4.6; 95% CI, 1.5-13.8). Lower urinary specific gravity (P = 0.015), and leukocyturia (P<0.001) were frequently associated features of indinavir nephropathy. No patient developed severe renal impairment and abnormalities were reversible upon discontinuation of the drug. Complications (renal colic, or pain and dysuria) occurred after a mean of 36 weeks (95% CI, 23-48) of indinavir treatment in 13 subjects (12.3%), eight of whom (62%) presented elevated creatinine during follow-up. Only long-term exposure to TMP-SMX (>160 weeks) was identified as a potential risk for the occurrence of a clinical event (OR, 4.7; 95% CI, 1.2-19.2).. A crystal nephropathy, characterized by serum creatinine elevation, loss of concentrating ability of the kidney, leukocyturia, and renal parenchymal image abnormalities, is a frequent complication of indinavir therapy. Identification of individuals at risk, particularly those with low body mass index or receiving TMP-SMX prophylaxis, may help the decision to initiate indinavir or chose an alternative protease inhibitor in order to minimize renal and urinary tract adverse events.

Topics: Adult; Creatinine; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Failure, Chronic; Kidney Function Tests; Male; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urologic Diseases

Topics: Acute Disease; Adult; Anti-HIV Agents; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Hypertriglyceridemia; Male; Pancreatitis; Reverse Transcriptase Inhibitors; Ritonavir; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The 12th World AIDS Conference in Geneva provided evidence that STD prophylaxis/treatment does not reduce HIV transmission. New guidelines for antiretroviral therapy in terms of when to treat and when to change are also presented. Research findings and practical applications are also provided for the following areas: HIV therapeutic monitoring, immune reconstitution, prevention, TMP-SMX prophylaxis, lipodystrophy, serum lipid changes, and diabetes.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Diabetes Complications; Drug Therapy, Combination; HIV Infections; Humans; Lipids; Lipodystrophy; Managed Care Programs; Practice Guidelines as Topic; Sexually Transmitted Diseases; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Viral Load

Topics: Adult; Anti-HIV Agents; Cytochrome P-450 Enzyme System; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Hypnotics and Sedatives; Lamivudine; Liver; Male; Midazolam; Saquinavir; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Adult; Anti-HIV Agents; Anti-Infective Agents; Deafness; Drug Therapy, Combination; Female; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine

Topics: Anti-Infective Agents; Drug Hypersensitivity; HIV Infections; Humans; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Absent for several decades, the chancroid reappeared in Algeria in 1988. In the unique department of Dermatology and Venereology of the University Hospital of the country of Tlemcen (more than 700,000 inhabitants), we wanted to know the state of this STD seven years after the report of the first cases. The file of the consulting patients were examined. We looked for the principal characteristics of this STD: age, sex, incubation period, place infection contact, type of relation, clinical presentation, evolution without and with treatment, other associated STD (syphilis, HIV). From August 1988 (1st case) to December 1995, 144 cases of chancroid were collected = 1988: 6, 1989: 5, 1990: 7, 1991: 18, 1992: 11, 1993: 33, 1994: 48, 1995: 16. The presentation is quite stereotyped; it concerns males only, singles in must cases, having had sexual relations with prostitutes. The incubation period is short (less than 10 days), the characteristic ulceration presents, very often, some adenopathies. The treatment by cotrimoxazole is efficient. They are no concomitant syphilis or HIV infection. The chancroid is the first cause of genital ulceration in the world. Since 1991, it is the principal STD in our department. It spreads within a male population, young singles associated with prostitutes. It is well installed in Algeria, and its role, although minor, in the transmission of the HIV infection, should not be neglected.

Topics: Adolescent; Adult; Age Factors; Algeria; Anti-Infective Agents; Chancroid; Genital Diseases, Male; HIV Infections; Humans; Lymph Nodes; Male; Marital Status; Middle Aged; Penile Diseases; Retrospective Studies; Scrotum; Sex Factors; Sex Work; Sexual Partners; Sexually Transmitted Diseases, Bacterial; Skin Ulcer; Syphilis; Trimethoprim, Sulfamethoxazole Drug Combination

To describe an outbreak of trimethoprim-sulfamethoxazole (cotrimoxazole)-resistant and methicillin-resistant Staphylococcus aureus (CMRSA) in a unit housing patients infected with the human immunodeficiency virus (HIV).. Prospective study involving patients colonized or infected with CMRSA.. 15 hospitalized patients with cultures positive for CMRSA.. Isolates of CMRSA were collected and characterized. Molecular typing of the epidemic strains was carried out after total DNA extraction by restriction endonuclease analysis and random amplification of polymorphic DNA.. The epidemic was brought under control with the reinforcement of nosocomial transmission measures and with systematic nasal decontamination with mupirocin of all patients admitted to the HIV unit. Molecular typing techniques showed the existence of two epidemic strains: strain A was present in the 12 patients admitted to the HIV unit and strain B in the remaining 3 patients hospitalized elsewhere.. Cotrimoxazole may no longer be a reliable and effective alternative for glycopeptides in patients with infection caused by MRSA strains, and HIV units should be particularly alert for CMRSA strains.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Female; HIV Infections; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Spain; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anaphylaxis; Anti-Infective Agents; Desensitization, Immunologic; Diagnosis, Differential; Drug Hypersensitivity; HIV Infections; Humans; Shock, Septic; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Listeriosis in HIV infected patients is uncommon and usually presents as meningitis or bacteraemia. Pleural fluid infections caused by this organism are extremely rare. A case is described of empyema caused by Listeria monocytogenes in an HIV infected patient that was successfully treated with medical treatment only.

Topics: Adult; Ampicillin; Anti-Infective Agents; Drug Therapy, Combination; Empyema, Pleural; Female; Gentamicins; HIV Infections; Humans; Listeriosis; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical course of HIV infection is frequently different among infants and children from that in adults. In adults among the most common sources of morbidity related to therapy are adverse drug reactions, notably to trimethoprim-sulfamethoxazole. Although there are case reports of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection, the precise rate and clinical characteristics of these adverse reactions among HIV-infected children are unknown.. We reviewed the clinical records of all children referred to a regional HIV clinic in a 6-year period. Therapy and suspected adverse drug reactions to therapy were reviewed by one of the investigators not involved in patient care. Adverse drug reactions were identified and characterized according to previously established criteria.. During this time 78 children were referred for assessment of possible HIV infection, 45 of whom were ultimately determined to have the infection. Twenty-five were treated with trimethoprim-sulfamethoxazole, 15 (60%) of whom tolerated therapy and 10 (40%) of whom had adverse reactions. The most common type of adverse reaction was erythema multiforme (70%), followed by neutropenia (20%) and Stevens-Johnson syndrome (10%). In two patients a serious adverse reaction to trimethoprim-sulfamethoxazole led to the diagnosis of HIV infection.. The overall incidence and type of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection appear to be similar to those among adults.

Topics: Anti-Infective Agents; Child; Child, Preschool; Female; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

In a case-control study, prophylaxis with cotrimoxazole for toxoplasmic encephalitis (TE) in HIV-infected patients was evaluated. Cotrimoxazole had been given as PCP prophylaxis. 20 patients with TE were identified and 72 matching control cases were found. All patients had IgG-antibodies to Toxoplasma gondii and CD4+ T-cell counts < or = 100/microliter. The use and duration of cotrimoxazole prophylaxis were recorded. It was found that among the patients with TE, none had used cotrimoxazole for > 70% of the observation time, and that the 1-y incidence was 0% in the control group vs. 41% in those patients without sufficient cotrimoxazole use. The conclusion is that cotrimoxazole is effective as primary prophylaxis for TE, even in a dose of 480 mg daily.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Female; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the safety of dapsone prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with prior intolerance to trimethoprim/sulfamethoxazole (TMP/SMX).. We conducted a retrospective study in the categorical human immunodeficiency virus out-patient program of a university hospital. Patients who had filled prescriptions for dapsone at our pharmacy between January 1991 and April 1994 were evaluated and 75 patients were found eligible for analysis.. The overall incidence of adverse events (AE) in our study cohort was 39%. The most common AEs were anemia (23%) and rash (16%). However, after critical evaluation of each case, only 3 cases of anemia (4%) and 2 cases of rash (3%) were judged to be "likely related" to dapsone. Only 5/75 patients (7%) developed the same intolerance to dapsone as previously experienced on TMP/SMX, and none of these cases was viewed as "likely related" to dapsone. A dapsone regimen of 100 mg qd and a prior episode of PCP were associated with a higher incidence of AEs. Eight cases of PCP occurred in spite of dapsone prophylaxis for an incidence of 7 cases per 1,000 patient-months. Seven of the cases of PCP occurred in patients who were receiving secondary prophylaxis.. Given the low incidence of AEs judged to be "likely related" to dapsone, this drug is a reasonable choice for PCP prophylaxis in patients with prior AEs to TMP/SMX.

Topics: Adult; Anti-Infective Agents; Anti-Infective Agents, Urinary; Dapsone; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Drug therapies for patients with human immunodeficiency virus (HIV) infection are associated with adverse events that can potentially limit their effectiveness. We sought to quantify the incidence of these events in clinical practice and determine whether there were demographic and clinical differences in adverse event rates for these drugs.. We calculated specific and overall adverse event rates from use of zidovudine, didanosine, zalcitabine, cotrimoxazole, and dapsone in an observational urban cohort of 1,450 HIV-infected patients with a CD4+ count of 500 cells/mm3 or less. We compared adverse event rates by gender, race, age, injecting drug use, and CD4+ count.. Overall adverse event rates in order of incidence were dapsone, 16.2 per 100 person-years (PY); didanosine, 24.1 per 100 PY; zidovudine, 26.3 per 100 PY; cotrimoxazole, 26.3 per 100 PY; and zalcitabine, 37.0 per 100 PY. Rates increased significantly with decline in CD4+ count from > 200 to < 100 cells/mm3 for all drugs but dapsone. In addition, women were more likely than men to have an adverse event for didanosine (relative risk [RR] = 2.7, P = 0.03) and from cotrimoxazole (RR 1.5; P = 0.05). Whites were at greater risk than blacks for adverse events from cotrimoxazole (RR = 1.6, P = 0.03). Only 22 of 357 total events (6%) required hospitalization, and there were no deaths.. Adverse events from antiretroviral drugs and Pneumocystis carinii pneumonia prophylaxis that interrupt therapy are relatively common, although serious events requiring hospitalization are rare. Adverse event rates increase progressively with decline in CD4+ count. The gender and race of the patient modify the risk of adverse events for some drugs.

Topics: Adult; Antiviral Agents; CD4 Lymphocyte Count; Dapsone; Didanosine; Female; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Health; Zalcitabine; Zidovudine

Meningitis is a frequent complication of the human immunodeficiency infection. Possible causes include bacterial, fungal, mycobacterial, syphilitic, and vital pathogens (including the human immunodeficiency virus). Drugs must also be considered in the differential diagnosis. Two patients with probable trimethoprim-sulfamethoxazole-induced meningitis are described in the setting of human immunodeficiency virus infection.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Male; Meningitis, Aseptic; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether HIV-infected patients have a deficiency of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) and erythrocytes.. Initial experiments determining the stability of intracellular GSH preceded the measurement of GSH levels in 33 HIV-positive patients and 40 control subjects within 1 h of isolation of their blood cells. In addition, the susceptibility of erythrocytes to dapsone hydroxylamine-induced methaemoglobinaemia was evaluated.. GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically.. GSH levels remained stable for only 1 h after cell isolation, thereafter showing a decrease of 20 and 60% at 4 and 24H, respectively, There was no difference in the GSH levels in PBMC and erythrocytes of the HIV-positive patients compared with controls. The GSH levels were not related to the disease stage or to CD4+ cell counts. There was no difference in GSH levels in PBMC taken from trimethoprim-sulphamethoxazole-hypersensitive and non-hypersensitive patients. Methaemoglobinaemia on exposure of erythrocytes to dapsone hydroxylamine was concentration-dependent, but there was no significant difference between patients and controls.. In contrast to previous studies, no deficiency of intracellular GSH in the PBMC and erythrocytes of HIV-infected patients was found. The discrepancy between studies may be methodological reflecting the instability of GSH, which requires prompt sample analysis.

Topics: Adult; Aged; CD4 Lymphocyte Count; Dapsone; Drug Hypersensitivity; Erythrocytes; Glutathione; HIV Infections; Humans; Leukocytes, Mononuclear; Male; Methemoglobinemia; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Although trimethoprim-sulfamethoxazole is the preferred chemoprophylaxis against Pneumocystis carinii pneumonia, there are frequent IgE-mediated reactions among children infected with the human immunodeficiency virus (HIV). Oral desensitization allows more patients to receive chemoprophylaxis, but it has been studied in only a limited number of children.. We desensitized five children infected with the HIV using a rapid, 4-h oral protocol.. Three children (including two infants) successfully completed desensitization and started maintenance therapy, but the other two experienced reactions that precluded further administration of trimethoprim-sulfamethoxazole.. We conclude that a rapid, oral trimethoprim-sulfamethoxazole desensitization protocol is safe and, in some instances, effective among HIV-infected children and infants with a history of non-life-threatening, IgE-mediated reactions to trimethoprim-sulfamethoxazole.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; Child; Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Infant; Lymphocyte Count; Male; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of standard-dose trimethoprim/sulfamethoxazole (TMP/SMX) (TMP 160 mg and SMX 800 mg q12h) on the serum potassium concentration.. Retrospective and concurrent study.. A Veterans Affairs Medical Center.. Fifty-three men hospitalized at the Fargo Veterans Affairs Medical Center. Thirty-three patients who received standard-dose TMP/SMX for 3 or more days comprised the study group. Twenty patients who received oral cephradine or amoxicillin for 3 or more days comprised the control group. Patients who received potassium supplements, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, nonsteroidal antiinflammatory drugs, beta-blockers, heparin, known nephrotoxic agents, patients with a serum creatinine concentration of more than 177 mumol/L, and patients with baseline hyperkalemia (serum potassium concentration > 5.1 mmol/L) were excluded.. The serum potassium concentration in the study group was 4.22 +/- 0.40 mmol/L and increased by 0.31 +/- 0.38 mmol/L at the end of therapy (p < 0.001). Twenty-six patients in the study group (78.8%) had an increase in the serum potassium concentration during TMP/SMX therapy. Fourteen of these patients had follow-up serum potassium concentrations obtained after completion of therapy. The serum potassium concentration returned to baseline in 10 of these patients. The serum creatinine concentration also increased during therapy. However, the correlation between the increase in the serum potassium concentration and the increase in the serum creatinine concentration was weak (Pearson r = 0.29). The serum potassium in the control group was 4.34 mmol/L and remained essentially unchanged during therapy.. Therapy with standard-dose TMP/SMX is associated with a slight increase in the serum potassium concentration. Routine monitoring of the serum potassium concentration in patients who are treated with standard-dose TMP/SMX therapy is unnecessary. However, TMP/SMX should be considered as a possible cause of unexplained hyperkalemia in elderly patients receiving TMP/SMX therapy.

Topics: Aged; Anti-Infective Agents, Urinary; HIV Infections; Humans; Hyperkalemia; Male; Potassium; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Mycoplasma have been suggested as co-factors in the pathogenesis of acquired immune deficiency syndrome (AIDS). The prevalence of urethral infection by Mycoplasma genitalium was determined by polymerase chain reaction (PCR) with urethral swabs from 35 HIV-infected patients at different stages of the disease (all of them were heterosexual men). M genitalium was detected in 2 out of 19 non-AIDS (stage A and B) patients and in a similar proportion (1 out of 14; 7.1%) of samples from healthy individuals. A dramatic increase in the frequency of M. genitalium detection was observed in samples of AIDS (stage C) patients. In fact, 9 out of 16 (56.2%) specimens tested positive by PCR. We found no association in AIDS patients between M. genitalium infection and CD4 count, Human Immunodeficiency Virus (HIV) p24 antigenemia or opportunistic infection.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents, Urinary; DNA, Bacterial; HIV Infections; HIV Seronegativity; Humans; Male; Mucous Membrane; Mycoplasma; Mycoplasma Infections; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination; Urethra; Urethritis; Zidovudine

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line drug for prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) and for prophylaxis of toxoplasmosis in HIV-infected patients. Evidence indicating intolerance related to the dose of SMX led us to examine the efficacy of altered TMP-SMX ratios in a corticosteroid-treated rat model. Infections were assessed by counting P. carinii cysts in lung and by titration of Toxoplasma gondii burdens in tissue culture. For prophylaxis, the reference regimen of 20 mg/kg TMP plus 100 mg/kg SMX was effective. Reduced doses of SMX (5 and 20 mg/kg) effective against PCP were effective against toxoplasmosis, provided the TMP dose was increased to 100 mg/kg. For curative treatment, the reversed ratio of 100 mg/kg TMP plus 20 mg/kg SMX was not effective. These results may provide a basis for altering the TMP-SMX ratios in setting of prophylaxis for both infections, especially in HIV infected patients who often poorly tolerate sulfonamides.

Topics: Animals; Anti-Infective Agents; Cells, Cultured; Dose-Response Relationship, Drug; Fluorescent Antibody Technique, Indirect; HIV Infections; Lung; Male; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Wistar; Toxoplasma; Toxoplasmosis, Animal; Trimethoprim, Sulfamethoxazole Drug Combination

The records of 206 patients with advanced infection due to human immunodeficiency virus type 1 who were receiving prophylaxis with clindamycin/primaquine (C/P), trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone to prevent Pneumocystis carinii pneumonia (PCP) were retrospectively examined. Two hundred sixty-two patient-years of prophylaxis were accrued (176.2 of TMP-SMZ, 63.4 of dapsone, and 22.8 of C/P). The rates of PCP in the TMP-SMZ, dapsone, and C/P groups were 3.4, 11.0, and 30.7 per 100 patient-years, respectively. Pairwise comparisons showed C/P to be less effective than TMP-SMZ (relative risk [RR], 9.02; 95% confidence interval [CI], 3.03-26.83). A similar trend was apparent for C/P vs. dapsone (RR, 2.78; 95% CI, 0.98-7.93). When only those receiving primary prophylaxis were analyzed, C/P recipients remained at greater risk than TMP-SMZ recipients (RR, 13.19; 95% CI, 3.54-49.12) and dapsone recipients (RR, 3.85; 95% CI, 1.12-13.31). Failure of C/P prophylaxis could be due, at least in part, to underdosing (clindamycin, 300 mg/d; primaquine, 15 mg/d). C/P recipients had more nonspecific diarrhea than did TMP-SMZ recipients (RR, 2.99; 95% CI, 1.61-5.55).

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; CD4 Lymphocyte Count; Clindamycin; Dapsone; Diarrhea; Drug Hypersensitivity; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Hematologic Diseases; HIV Infections; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the effect of the type of Pneumocystis carinii pneumonia (PCP) prophylaxis on the development of community-acquired bacteremia.. Case-control study using all cases of community-acquired bacteremia identified prospectively during a longitudinal study of all infections in a cohort of HIV-infected persons.. University-affiliated Department of Veterans Affairs Medical Center HIV program.. All patients with community-acquired bacteremia seen at the facility between January 1990 and December 1995 were included. Controls, seen at the same facility and matched by date and CD4 count, were used to assess risk factors. A total of 57 cases and 114 controls were analysed.. Risk of development of bacteremia, distribution of organisms, and effect of specific prophylactic regimens for PCP.. Bacteremia was caused by Staphylococcus aureus (23%), Pseudomonas aeruginosa (18%), Escherichia coli (16%), Streptococcus pneumoniae (14%) and others (31%). Groups were similar by age, race, HIV risk factors and CD4 count. The presence of an intravenous catheter was mildly predictive of the development of bacteremia [odds ratio (OR), 2.67; P = 0.024]. Type of PCP prophylaxis in cases and controls with CD4 < 200 x 10(6)/l included co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX; 31 and 60%, respectively), dapsone (33 and 24%, respectively) and aerosolized pentamidine (27 and 13%, respectively). Use of TMP-SMX (but not dapsone or aerosolized pentamidine) was associated with the absence of bacteremia (OR, 0.28; P = 0.001). A similar protective effect was found when controlling for the presence of an intravenous catheter.. PCP prophylaxis with TMP-SMX apparently protects against community-acquired bacteremia in HIV-infected persons.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bacteremia; Community-Acquired Infections; Dapsone; HIV Infections; HIV-1; Humans; Male; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the safety and efficacy of an in-patient oral desensitization regimen in HIV- infected patients hypersensitive to trimethoprim-sulfamethoxazole (TMP-SMX).. TMP-SMX was given orally once a day using incremental doses every day, starting with 0.4 mg TMP/2 mg SMX at day 4 and achieving a full dosage of TMP-SMX (80 mg/400 mg) at day 5. Success was defined as clinical tolerance of the final dose for more than 10 days following completion of the procedure.. Desensitization was successfully completed in 29 of 30 patients. A transient rash occurred in one patient during desensitization and resolved without need for discontinuation of the desensitization protocol. The procedure failed in one patient who experienced sustained moderate cutaneous reaction with fever on day 5.. Our results suggest the safety and efficacy of an inpatient oral desensitization regimen in 30 HIV-infected patients who had experienced cutaneous reactions to trimethoprim-sulfamethoxazole (TMP-SMX). Specific desensitization to TMP-SMX allows to circumvent the limitations towards effective prophylaxis of PCP that are dependent on the occurrence of cutaneous reactions to the drug.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; Female; HIV Infections; HIV-1; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Chancroid; Ciprofloxacin; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

To measure the incidence of cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary Pneumocystis carinii pneumonia (PCP) prophylaxis: to measure the incidence of severe reactions: and to identify predictors for these outcomes.. Retrospective cohort study.. One university-based outpatient HIV clinic and one university-affiliated internal medicine and infectious disease medical practice.. Two hundred thirty-six HIV-infected individuals receiving cotrimoxazole for primary PCP prophylaxis.. None.. Occurrence of a cutaneous hypersensitivity reaction, defined as rash, fever, or pruritus that resulted in permanent discontinuation of cotrimoxazole. Severe reactions were defined as those resulting in hospital admission or systemic treatment with a corticosteroid. Cox regression was used to calculate relative rates (RRs) and 95% confidence intervals (CIs) for a number of clinical and laboratory variables.. Forty-eight (20%) subjects developed cutaneous hypersensitivity reactions, with six (12.5%) of these being severe. In the unadjusted analysis, the following factors demonstrated at least borderline association: male gender [RR (95% CI) = 0.46 (0.21-0.99)], higher CD4 percentage [RR (95% CI) = 0.95 (0.90-1.00)], syphilis history [RR (95% CI) = 0.37 (0.13-1.04)], and higher total protein [RR (95% CI) = 0.70 (0.45-1.09)]. Adjustment for potential confounding by measured variables did not meaningfully change these results.. Cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary PCP prophylaxis are common. Although male gender, higher CD4 percentage, syphilis history, and higher total protein have at least borderline associations with these reactions, routinely collected clinical and laboratory variables do not appear to be sufficiently associated with the reactions to permit development of a clinically useful prediction rule.

Topics: Adult; Aged; Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Cohort Studies; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Female; HIV Infections; HIV Seropositivity; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Mass Screening; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in children who have acquired immunodeficiency syndrome (AIDS). Despite the publication of guidelines for prophylaxis against PCP for children infected with human immunodeficiency virus (HIV) in 1991 (1), ongoing AIDS surveillance has detected no substantial decrease in PCP incidence among HIV-infected infants. Studies indicate that this continued incidence is associated with failure to identify HIV-infected children before PCP occurs and with limitations in the ability of CD4+ measurements to identify children at risk for PCP. In March 1994, the National Pediatric & Family HIV Resource Center, in collaboration with CDC, convened a working group to review additional data about the occurrence of PCP among HIV-infected children and to reevaluate the 1991 PCP prophylaxis guidelines for children. This report summarizes these new data and presents revised PCP prevention guidelines that recommend a) promptly identifying children born to HIV-infected women and initiating regular diagnostic and immunologic monitoring of such children; b) beginning PCP prophylaxis at 4-6 weeks of age for all children who have been perinatally exposed to HIV; c) continuing prophylaxis through 12 months of age for HIV-infected children; and d) making decisions regarding prophylaxis for HIV-infected children > or = 12 months of age based on CD4+ measurements and whether PCP previously has occurred.

Topics: AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Chemoprevention; Child, Preschool; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis.. Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL).. Occurrence or recurrence of PCP.. A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03).. These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Dapsone; HIV Infections; HIV-1; Humans; Immune Tolerance; Longitudinal Studies; Male; Multivariate Analysis; Pentamidine; Pneumonia, Pneumocystis; Proportional Hazards Models; Recurrence; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

The cutaneous manifestations of human immunodeficiency virus infection include papulosquamous diseases, viral and fungal infections, and neoplastic disorders. Eczematous photosensitivity disorders have been reported in patients infected with the human immunodeficiency virus. We describe a patient with advanced acquired immunodeficiency syndrome who developed photodistributed hypertrophic lichen planus. We believe this is a distinct cutaneous manifestation of human immunodeficiency virus infection.

Topics: Adrenal Cortex Hormones; Adult; Biopsy; Dapsone; HIV Infections; Humans; Lichen Planus; Male; Photosensitivity Disorders; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Child; HIV Infections; Humans; Immunoglobulins, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

Antiretroviral and prophylactic therapy given to HIV-infected patients attending hospital (DMI 2 data base) was analyzed according to TCD4+ cell count; 19,020 patients were included in the study. Under 200 TCD4+/mm3, more than 80% of the patients received antiviral therapy, most often AZT (45.3%) or ddI (27.2%). Combined treatment was quite low, less than 8%. Although above 500 TCD4+/mm3, 11.6% of patients received AZT, this study showed that antiretroviral therapy followed French recommendations. This was not the case for prophylaxis: a large proportion of patients under 200 TCD4+/mm3 did not received pentamidine aerosol, or cotrimoxazole, or dapsone.

Topics: Anti-Infective Agents; Antiviral Agents; CD4 Lymphocyte Count; Dapsone; Didanosine; Drug Utilization; France; HIV Infections; Hospital Information Systems; Hospital Records; Humans; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine; Zidovudine

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; HIV Infections; Humans; Ketoconazole; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is common in children and adults who are HIV-positive. More than half of the babies who have PCP never received preventive drugs. It is suggested that a greater number of HIV-exposed infants must be identified at an earlier stage, and preventive medication should be prescribed. It is further recommended that HIV testing and monitoring be made more available to infants at risk so that preventive PCP medication can be given at four to six weeks of age, regardless of the CD4 count and HIV test results. The first choice of treatment is Bactrim or Septra. More information can be obtained by calling the Network at (800) 734-7104.

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; HIV Infections; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Allogenic proteins that contaminate intermediate purity clotting factor concentrates may activate the immune system of HIV-infected haemophilic patients. In 37 haemophilic patients infected with HIV who had originally been treated with intermediate purity factor VIII concentrate and then changed to monoclonally-purified high purity factor VIII concentrate the rates of CD4+ decline (10(9)/l per year) were 0.06 before and 0.02 after a switch to high purity products (p = 0.01). The median follow-up of patients after the switch to high purity products was 1.7 years (range 0.2 to 3 years). This significant change in the rate of CD4 decline was independent of the starting CD4 count, age and antiretroviral therapy. This result is consistent with those from randomised trials of the introduction of high-purity concentrate. Given the strong association between the CD4+ count and survival, treatment with high purity rather than intermediate purity clotting factor concentrate may confer a survival benefit for HIV-infected haemophilic patients.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Child; Child, Preschool; Cohort Studies; Disease Progression; Factor VIII; Fluconazole; Hemophilia A; HIV Infections; Humans; Male; Middle Aged; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Child, Preschool; Dapsone; HIV Infections; Humans; Infant; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the pancreatic beta cells function of HIV patients receiving either 300 mg per month of aerosolized pentamidine (n = 12) or oral trimethoprim-sulfamethoxazole (TMP-SMX), twice a day three times per week (TMP: 160 mg, SMX: 800 mg) (n = 10). Intravenous (i.v.) glucose tolerance tests were performed after i.v. injection of 0.5 glucose by kg of body weight in 30 seconds. Plasma insulin levels were assessed at baseline, 1, 2, 3 and 5 min. Moreover, in patients receiving inhaled pentamidine, plasma glucose amylase and insulin levels were measured every 30 min for 2 hours after the end of the aerosol. Plasma pentamidine levels were measured 30 min after the end of the aerosol. Those tests were performed every 2-3 months for one year. In most patients taking aerosol treatment, pentamidine levels were detectable, remaining under levels of 50 ng/ml. Pentamidine plasma levels increased in a time dependent manner. Baseline plasma glucose, amylase and insulin levels were in normal range and remained stable during the therapy. For 7 out of 12 patients, glucose tolerance tests showed an adequate insulin secretion: the addition of the two best insulin levels were higher than 70 IU/ml. When this criteria was not found (n = 5), a glucagon stimulation test allowed to exclude an endocrine pancreatic dysfunction. Due to its apparent short half-life, increased pentamidine levels could be related to an improvement of spray techniques as well as to a cumulative effect. Pancreatic function was preserved in pentamidine-treated patients compared to TMP-SMX-treated patients.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; HIV Infections; HIV Seropositivity; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy of primary chemoprophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in infants with perinatal human immunodeficiency virus-1 infection during the first year of life, we conducted a retrospective chart review of infants with human immunodeficiency virus-1 infection born at New York University Medical Center-Bellevue Hospital Center, in New York. Between March 1989 and March 1993, 24 infants received primary chemoprophylaxis with trimethoprim-sulfamethoxazole in the first year of life and 24 infants did not receive primary prophylaxis. The CD4+ T-lymphocyte counts in the two groups did not differ during the first year of life. The median age at the time of initiation of prophylaxis was 3 months, and the average duration of prophylaxis was 5.5 months. Among the infants who had not received prophylaxis, five cases of PCP were diagnosed at a median age of 5 months; in contrast, no cases of PCP were observed in the infants receiving prophylaxis (log-rank test, p = 0.017). The probability of surviving after 1 year of age was 92% for the children who received prophylaxis and 74% for those who did not (log-rank test, p = 0.035). These data indicate that chemoprophylaxis is highly effective in preventing primary PCP and improving survival time in infants with human immunodeficiency virus-1 infection.

Topics: Age Factors; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Cohort Studies; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Leukocyte Count; Male; Pneumonia, Pneumocystis; Probability; Retrospective Studies; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Female; HIV Infections; HIV Seropositivity; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the prevalence and clinical manifestations of Cyclospora in Haitians infected with human immunodeficiency virus (HIV) who have diarrhea and to evaluate therapy and prophylaxis.. Cohort study. From 1990 to 1993, stool samples were collected from adults seropositive for HIV who had had diarrhea for at least 3 weeks.. A clinic in Haiti.. Stool samples were examined for enteric protozoa after acid-fast staining. Patients with Cyclospora infection were treated with trimethoprimsulfamethoxazole (160 mg and 800 mg, respectively) given orally four times a day for 10 days. After completion of therapy, patients were evaluated weekly and re-treated if clinical and parasitologic recurrences occurred, followed by trimethoprim-sulfamethoxazole prophylaxis three times a week.. 804 of 2400 patients (33%) seropositive for HIV had a history of chronic or intermittent diarrhea; 502 of these 804 patients (62%) currently had diarrhea, and 450 patients each provided two stool specimens for examination. Enteric protozoa identified included Cryptosporidium (30%), Isospora belli (12%), Cyclospora species (11%), Giardia lamblia (3%), and Entamoeba histolytica (1%). Forty-three patients with diarrhea and Cyclospora infection were studied; their symptoms were indistinguishable from those seen in patients with isosporiasis or cryptosporidiosis. In all patients, diarrhea ceased and results from stool examinations were negative within 2.5 days after beginning oral trimethoprim-sulfamethoxazole therapy. Recurrent symptomatic cyclosporiasis developed in 12 of 28 patients (43%) followed for 1 month or more, but it also responded promptly to trimethoprim-sulfamethoxazole therapy. These 12 patients received trimethoprim-sulfamethoxazole three times a week as secondary prophylaxis, with only a single recurrence after 7 months.. Cyclospora infection is common in Haitian patients with HIV infection, responds to trimethoprim-sulfamethoxazole therapy, and has a high recurrence rate that can be largely prevented with long-term trimethoprim-sulfamethoxazole prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Coccidiosis; Cohort Studies; Diarrhea; Eucoccidiida; Feces; Female; Haiti; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) is more common in patients with HIV infection. In non-infected patients, TMP-SMX hypersensitivity is more common in those with a slow acetylator phenotype. This study was conducted to determine whether the slow acetylation phenotype is associated with an increased risk of hypersensitivity to TMP-SMX in patients with HIV infection.. Acetylation phenotype was determined in 28 HIV-infected subjects, of whom 16 had prior TMP-SMX hypersensitivity and 12 had received long-term TMP-SMX therapy without hypersensitivity, as well as in 29 healthy controls. Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (AAMU) and 1-methylxanthine (1-MX), after ingestion of a single 200 mg dose of caffeine.. Of the 28 HIV-infected subjects, 20 (71%) expressed a slow acetylation phenotype and eight (29%) a fast phenotype. By comparison, of the 29 healthy controls, 15 (52%) expressed a slow phenotype (P = 0.11). Of the 16 HIV-infected subjects with prior TMP-SMX hypersensitivity, 15 (94%) had a slow acetylation phenotype, whereas only five out of 12 (42%) non-hypersensitive subjects had a slow acetylation phenotype (P < 0.01).. A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects.

Topics: Acetylation; Adult; Arylamine N-Acetyltransferase; Caffeine; Drug Eruptions; Female; HIV Infections; Humans; Male; Middle Aged; Phenotype; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Hypersensitivity; Fever; Heart Arrest; HIV Infections; Humans; Hypotension; Infant; Male; Respiratory Insufficiency; Tachycardia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: CD4-Positive T-Lymphocytes; HIV Infections; Humans; Leukocyte Count; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; CD4-Positive T-Lymphocytes; Cholestasis; Female; Hepatitis; HIV Infections; HIV-1; Humans; Immunoglobulins; Infant; Jaundice; Leukocyte Count; Liver; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cytomegalovirus; Drug Therapy, Combination; HIV Infections; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Infant; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Adult; AIDS-Related Opportunistic Infections; Bacterial Infections; Cohort Studies; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.

Topics: Cell Division; Cells, Cultured; Extracellular Matrix Proteins; Glomerular Mesangium; HIV Infections; Humans; Lipopolysaccharides; Macrophages; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutathione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-1 beta, IL-6 or tumour necrosis factor-alpha (TNF-alpha) by PBMC. The cytotoxicities of SMX and SMX-HA to PBMC were assessed in 45 HIV-infected patients with prior TMP-SMX therapy, and in eight HIV- controls. Twelve HIV-infected subjects were studied prospectively before primary Pneumocystis carinii pneumonia (PCP) therapy or rechallenge with TMP-SMX in previously hypersensitive subjects. Cytokine production was measured in four hypersensitive and two non-hypersensitive HIV-infected subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infected patients with prior hypersensitivity than both the 23 HIV-infected patients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutathione only in the hypersensitive group. SMX did not induce cytotoxicity in any group. In 12 subjects studied prospectively, SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1 beta and TNF-alpha, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensitivity to TMP-SMX in HIV-infected patients, and that in vitro cytotoxicity could be useful in the diagnosis of hypersensitivity and predicting its likelihood.

Topics: Adult; CD4-CD8 Ratio; Cytokines; Cytotoxicity, Immunologic; Drug Hypersensitivity; Glutathione; HIV Infections; Humans; Male; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX.. A prospective, open study.. A tertiary referral hospital.. Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX.. Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week).. That rechallenge is more likely to be successful in those with advanced HIV disease.. Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred.. Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

Topics: Adult; AIDS-Related Opportunistic Infections; Cross Reactions; Drug Eruptions; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumocystis Infections; Safety; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Drug Hypersensitivity; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Cholestasis; Giant Cells; Hepatitis, Viral, Human; Hepatomegaly; HIV Infections; HIV Seropositivity; Humans; Infant; Liver; Pentamidine; Pneumonia, Pneumocystis; Splenomegaly; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Administration, Oral; Adolescent; Adult; Aerosols; CD4-Positive T-Lymphocytes; Child; Clinical Protocols; HIV Infections; Humans; Leukocyte Count; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

In 1989, the United States Public Health Service convened a Task Force of experts to consider the expanding knowledge base about prevention of Pneumocystis carinii pneumonia (PCP) among adults and adolescents (greater than or equal to 13 years of age) with human immunodeficiency virus (HIV) infection. This Task Force concluded that the morbidity, mortality, and cost due to PCP could be substantially reduced by appropriate use of antipneumocystis prophylaxis in subgroups of HIV-infected patients known to be at high risk, and developed recommendations for the administration of prophylactic regimens (1). The recommendations state that CD4+ T-lymphocyte counts should be monitored prospectively at 3- to 6-month intervals and prophylaxis should be instituted when patients become immunologically susceptible to PCP. Susceptibility was defined by a CD4+ T-lymphocyte count less than 200 cells/microliters or less than 20% of total circulating lymphocytes, or the occurrence of a previous episode of PCP. The goal of this approach was to reduce the frequency both of initial episodes of PCP (primary prophylaxis) and of relapses or recurrences (secondary prophylaxis). Either oral trimethoprim-sulfamethoxazole (TMP-SMX) or aerosol pentamidine was recommended for prophylaxis, but because direct comparative data were lacking, neither regimen was endorsed as "preferred." Since the recommendations were issued in 1989, additional information has become available about the efficacy and safety of aerosol pentamidine and oral TMP-SMX. A trial sponsored by the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group compared these two regimens in a prospective randomized study; in August 1991, this study was terminated by an independent data and safety monitoring board because statistically significantly fewer recurrences of PCP were observed in the oral TMP-SMX group than in the aerosol pentamidine group (2). On the basis of this finding and other studies assessing PCP prophylaxis, the Task Force was reconvened on October 5, 1991. This report contains the revised recommendations issued by the Task Force.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; CD4-Positive T-Lymphocytes; Child; Clinical Protocols; HIV Infections; Humans; Leukocyte Count; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Topics: Administration, Inhalation; Administration, Oral; Adult; HIV Infections; Humans; Male; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; HIV Infections; Humans; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination

Several questions remain unanswered including the timing of perinatal transmission, maternal factors predisposing to perinatal transmission of HIV-1, the best methods for early diagnosis in the neonate, and means of preventing perinatal HIV-1 infection. Significant advances have been made in the early diagnosis of HIV-1 infection, and now it is possible to make a diagnosis in most infants by 6 months of age. Unfortunately, not all these techniques are commercially available, so this capability is limited to certain institutions and laboratories. The natural history of HIV-1 infection in children continues to evolve, particularly with increased prophylaxis of P. carinii pneumonia and the availability of antiretroviral therapy. Our challenges for the future are to prevent perinatal transmission, to develop new and better therapies for opportunistic infections and HIV-associated complications, and to improve outcome and prognosis.

Topics: Child, Preschool; Female; HIV Infections; HIV-1; Humans; Infant; Maternal-Fetal Exchange; Pneumonia, Pneumocystis; Pregnancy; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Drug Administration Schedule; HIV Infections; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: HIV Infections; Humans; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Although guidelines have been established for prophylaxis against Pneumocystis carinii pneumonia (PCP) for adults with human immunodeficiency virus (HIV) infection, they have not been available for children (1). Experts in pediatric HIV infection (convened by the Pediatric HIV Resource Center) independently reviewed recent data and provided recommendations to the U.S. Public Health Service for PCP prophylaxis for HIV-infected or -exposed children. This report summarizes these deliberations and details the consensus guidelines.

Topics: Aerosols; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Clinical Protocols; Dapsone; Drug Administration Schedule; HIV Infections; Humans; Infant; Leukocyte Count; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerosols; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Clinical Protocols; Dapsone; Drug Administration Schedule; HIV Infections; Humans; Infant; Leukocyte Count; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The case histories of 27 children with Pneumocystis carinii pneumonia (PCP) who were followed up in the AIDS Program at the Children's Hospital of New Jersey, Newark, are reviewed. The mean and median age at PCP diagnosis were 10.8 and 7.7 months, respectively. All of the children had other clinical evidence of infection with the human immunodeficiency virus that was documented prior to the diagnosis of PCP or found at the time of PCP diagnosis. Most patients who presented to the hospital were acutely ill, and complications of treatment occurred in 70%. Overall, 89% of the patients died and 70% survived for less than 6 months after diagnosis of PCP. Median survival after the diagnosis of PCP was only 2.0 months and the median life span of children with PCP was only 14.4 months. Only 40% of children with PCP had CD4 lymphocyte counts at or below the threshold for institution of PCP prophylaxis in adults of 200 x 10(6) cells/L (200 cells/mm3).

Topics: CD4-Positive T-Lymphocytes; Child, Preschool; Female; HIV Infections; Humans; Infant; Leukocyte Count; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Effective prophylaxis exists against Pneumocystis carinii pneumonia, a major cause of illness and death among human immunodeficiency virus-infected children and adults. While adults with CD4 counts less than 0.2 x 10(9)/L are at highest risk for Pneumocystis carinii, clinical or laboratory markers of high risk in children infected with the human immunodeficiency virus have not yet been established. A chart review of 13 infants with perinatally acquired human immunodeficiency virus infection and children with Pneumocystis carinii pneumonia revealed that infants younger than 12 months developed Pneumocystis carinii pneumonia despite CD4 counts that were normal by adult standards. In contrast to the markedly increased serum IgG levels seen in most children infected with the human immunodeficiency virus, five children with Pneumocystis carinii pneumonia had IgG levels less than 3.0 g/L. Twelve patients had pre-existing symptoms consistent with human immunodeficiency virus infection before the episode of Pneumocystis carinii pneumonia. In addition to clinical symptoms, low IgG levels and CD4 counts adjusted for age may serve to identify those children who are most at risk for Pneumocystis carinii pneumonia and therefore candidates for prophylaxis. Prophylaxis should be offered to all infants under age 12 months with proven, or clinical symptoms compatible with, human immunodeficiency virus infection. For children older than 12 months, CD4 counts less than 0.3 x 10(9)/L appear to be predictive of risk for Pneumocystis carinii pneumonia, and these children should also receive prophylaxis.

Topics: Biomarkers; CD4-Positive T-Lymphocytes; Child; Child, Preschool; HIV Infections; Humans; Immunoglobulin G; Infant; Lymphocyte Subsets; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Administration Schedule; Drug Interactions; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Child; Child, Preschool; Drug Administration Schedule; HIV Infections; Humans; Infant; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Child; Child, Preschool; HIV Infections; Humans; Infant; Infant, Newborn; Lung Diseases; Lung Neoplasms; Mycoplasma Infections; Mycoses; Opportunistic Infections; Pneumonia, Pneumocystis; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

Topics: Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: CD4-Positive T-Lymphocytes; HIV Infections; Humans; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerosols; CD4-Positive T-Lymphocytes; Clinical Protocols; Delivery of Health Care; France; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Clindamycin; Communicable Diseases; Fluconazole; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; CD4 Antigens; Child, Preschool; Follow-Up Studies; HIV Infections; Humans; Infant; Leukocyte Count; Pentamidine; Pneumonia, Pneumocystis; T-Lymphocytes, Helper-Inducer; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Topics: Acquired Immunodeficiency Syndrome; Drug and Narcotic Control; HIV Infections; Humans; Mouth Diseases; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Food and Drug Administration; Zidovudine