trimethoprim--sulfamethoxazole-drug-combination and AIDS-Related-Opportunistic-Infections

Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.

Topics: AIDS-Related Opportunistic Infections; Child; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Child, Preschool; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.

Topics: Adult; Aged, 80 and over; AIDS-Related Opportunistic Infections; Aspergillus fumigatus; Coinfection; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Fungal Infections; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Aspergillosis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bacterial Proteins; CD4 Lymphocyte Count; Dihydropteroate Synthase; Drug Resistance, Bacterial; HIV-1; Humans; Immunocompromised Host; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; 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

In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX.. We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients.. Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients.. CD4 cell count <200/μL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; HIV Seronegativity; Humans; Immunocompromised Host; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; 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

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

Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5 and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-folds higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-TB treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimized case management, which includes early initiation of ART (with timing now defined by randomized controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of comorbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require preventive interventions, including optimized immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multidrug-resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated healthcare delivery for TB, HIV and other comorbidities.

Topics: Acquired Immunodeficiency Syndrome; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Delivery of Health Care; Female; HIV Seropositivity; Humans; Incidence; Male; Mass Screening; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Tuberculosis, Multidrug-Resistant

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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Bronchoalveolar Lavage Fluid; Caspofungin; Diagnosis, Differential; Echinocandins; Humans; Lipopeptides; Lung; Opportunistic Infections; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

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

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

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; Anti-Infective Agents; Antiviral Agents; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

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 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

Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13-year-old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Azithromycin; Fever; Hemangioendothelioma; Humans; Lymph Nodes; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP).. We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs).. Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0]).. Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.

Topics: AIDS-Related Opportunistic Infections; Clindamycin; Cohort Studies; Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Inflammatory Agents; Antiprotozoal Agents; Biopsy; Bronchoscopy; CD4 Lymphocyte Count; Clindamycin; Dapsone; Developing Countries; Drug Therapy, Combination; Global Health; Humans; Oxygen Inhalation Therapy; Patient Selection; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Primaquine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies.. To compare the rate of discontinuation of cotrimoxazole and adverse reactions among the three strategies of treating-through, desensitization, and rechallenge in patients living with HIV who previously had an adverse reaction to cotrimoxazole.. We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National Institutes of Health Clinical Trials Registry, and CenterWatch (search date May 2006).. Randomised trials comparing treating-through, rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in adults (age 18 years or over) and/or children (age 17 years or under).. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details.. Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies.. In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

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

Co-trimoxazole prophylaxis in HIV-infected persons is beyond doubt one of the cheapest and most important interventions, next to antiretroviral therapy (ART), to improve survival. However, many questions, ranging from programme coverage and public health impact to individual tolerance and compliance, remain unanswered. Together with the need for more research to identify optimal ART regimens for resource-poor settings, research regarding optimal chemoprophylaxis against opportunistic infections should also remain high on the agenda.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Developing Countries; Drug Therapy, Combination; Humans; Treatment Outcome; 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

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

The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important cause of death and illness in the first year of life. It is safe with relatively few side effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life. Providing prophylaxis based initially on maternal status is one possible solution. 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 children with HIV infection, and in infants of HIV-infected mothers.. We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date Feb 2005). We checked reference lists of 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 children (age less than 15 years) with HIV infection, or children less than 18 months with HIV infected mothers.. Two reviewers independently assessed trial eligibility and quality. Where data were incomplete or unclear trial authors were contacted for further details.. One study was identified that fulfilled the inclusion criteria. It studied 534 children with HIV infection in Lusaka, Zambia. The study was conducted in an area of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk 0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation, relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse events between groups, and the beneficial effect was seen across all ages and CD4%.. A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.

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

Despite provisional recommendations from the World Health Organization and UNAIDS that cotrimoxazole (CTX) prophylaxis be offered to all individuals living with AIDS, including HIV-positive patients with TB, its routine use in developing countries particularly Africa has been minimal. Concerns were expressed regarding its effectiveness in areas of high bacterial resistance, that its widespread use might substantially increase bacterial cross-resistance in the community and that this intervention might promote resistance of malaria parasites to sulphadoxine-pyrimethamine. We review the current evidence on the above concerns and highlight the main operational considerations related to implementing CTX prophylaxis as a basic component of care for HIV-positive TB patients in developing countries.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Drug Resistance; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

We report a case of rhabdomyolysis associated with the use of trimethoprim-sulfamethoxazole (TMP-SMX) in a newly diagnosed AIDS patient with presumed Pneumocystis jiroveci (formerly named Pneumocystis Carinii) pneumonia. The present case is significant because of the paucity of similar cases in the literature and the relative frequency with which TMP-SMX is used today.

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

Cerebral toxoplasmosis or toxoplasmic meningoencephalitis (hereafter referred to as TE) was one of the first opportunistic infections to be described in human immunodeficiency virus (HIV) -infected patients. Treatment of TE has been relatively successful in comparison to other opportunistic infections. Prior to the introduction of highly active antiretroviral therapy (HAART), a median survival of over a year was reported for patients who could tolerate the toxicity of TE treatment. HAART is becoming increasingly widely available in sub-Saharan Africa, where the majority of HIV-infected patients live. Many patients in Africa are diagnosed with HIV only after developing opportunistic infections such as TE. Hence, the optimal management of opportunistic infections such as TE is important if the benefits of subsequently initiating HAART are to be seen.. The purpose of this review is to determine the most effective therapy for TE in HIV-infected adults. Different treatment regimens have been compared with regard to clinical and radiological response, mortality, morbidity, and serious adverse events.. A comprehensive search of relevant databases and other sources was conducted to identify relevant studies.. Randomised double-blinded trials were included.. Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software.. Three trials were found to meet the inclusion criteria. Dannemann et al 1992 and Katlama et al 1996 compared pyrimethamine plus sulfadiazine (P+S) with pyrimethamine plus clindamycin (P+C). Torre 1998 compared P+S with trimethoprim-sulfamethoxazole (TMP-SMX). For the purposes of this review, clinical outcomes were analysed as complete or partial resolution vs. failure. Patients who crossed over or were lost to follow-up were analysed as failures. Dannemann et al 1992 assessed 59 patients. Five of 26 (19%) patients randomised to P+C died in the first 6 weeks compared with 2 of the 33 (6%) patients randomised to P+S (relative risk (RR) 3.17; 95% CI 0.67-15.06). Complete or partial clinical response was obtained in 12 (46.2%) patients receiving P+C vs. 16 (48.5 %) patients receiving P+S (RR 0.95; 95% CI 0.55-1.64). Katlama et al 1996 assessed 299 patients. Twenty-nine (19%) of the 152 patients randomised to P+C died compared with 22 (15%) of the 147 patients randomised to P+S (RR 1.27; 95% CI 0.77-2.11). We were unable to obtain data on the outcomes of patients who crossed over and therefore excluded these data from the analysis. Dannemann et al 1992 and Katlama et al 1996 were analysed together for the outcome of death. The two treatment arms did not differ for death (RR 1.41; 95% CI 0.88-2.28). Torre et al 1998 assessed 77 patients. There were no deaths during the study period. Twenty-eight (70%) of 40 patients randomised to TMP-SMX had a complete or partial clinical response compared with 26 (70%) of 37 patients randomised to P+S (RR 1.0; 95% CI 0.74-1.33).. The available evidence fails to identify any one superior regimen for the treatment of TE. The choice of therapy will often be directed by available therapy. Given the current evidence, TMP-SMX appears to be an effective alternative therapy for TE in resource-poor settings where P+S are not available.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Clindamycin; Humans; Meningoencephalitis; Poverty; Pyrimethamine; Randomized Controlled Trials as Topic; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytokines; Humans; Macrophages; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Alveoli; 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

Infants with HIV infection are vulnerable to Pneumocystis carinii pneumonia (PCP) during their first year of life. WHO and the Joint United Nations Programme on HIV/AIDS now recommend that all children of HIV-positive mothers receive prophylactic cotrimoxazole against PCP from six weeks of age and continue this therapy until exposure through breast milk ceases-and the infant is confirmed to be HIV-negative (rarely before one year of age). Empirical prophylaxis invokes a trade-off between possible benefit to the infant versus the risk of resistance to antibiotics and antimalarials. From a critical analysis of the literature, we offer a conceptual model demonstrating how, under certain circumstances, a policy of mass cotrimoxazole prophylaxis may be counterproductive.

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Breast Feeding; Chemoprevention; Drug Resistance; Humans; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Topics: AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Humans; Immunocompromised Host; Intermittent Positive-Pressure Ventilation; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

The prevention and early treatment of infections are the mainstay of the medical management of the majority of children 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, including Pneumocystis carinii pneumonia (PCP) which is an important cause of death and illness in the first year of life. It is safe with relatively few side-effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life and providing prophylaxis based initially on maternal status is one possible solution. 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 children with HIV infection, and in infants of HIV infected mothers.. We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date July 2001). We checked reference lists of 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 children (age less than 13 years) with HIV infection, or children less than 18 months with HIV infected mothers.. Two reviewers independently assessed trial eligibility and quality.. No studies were found that fulfilled the selection criteria.. No evidence from controlled trials was found of the effect of cotrimoxazole prophylaxis in HIV-infected children.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Humans; Infant; 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: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

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

To determine the relative efficacies of alternative antipneumocystis agents in human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia unresponsive to primary drug treatment with a combination product of trimethoprim and sulfamethoxazole or parenteral pentamidine.. Meta-analysis of 27 published clinical drug trials, case series, and case reports involving P carinii pneumonia. Data extracted included underlying disease, primary antipneumocystis treatment, days of failed primary treatment, salvage regimen, use of systemic corticosteroids and antiretroviral drugs, and clinical outcome.. In 497 patients with microbiologically confirmed P carinii pneumonia (456 with HIV or acquired immunodeficiency syndrome), initial antipneumocystis treatment failed and they therefore required alternative drug therapy. Failed regimens included trimethoprim-sulfamethoxazole (160 patients), intravenous pentamidine (63 patients), trimethoprim-sulfamethoxazole and/or pentamidine (258 patients), aerosolized pentamidine (6 patients), atovaquone (3 patients), dapsone (3 patients), a combination product of trimethoprim and dapsone (2 patients), and trimethoprim-sulfamethoxazole followed by a combination of clindamycin and primaquine phosphate (2 patients). Efficacies of salvage regimens were as follows: clindamycin-primaquine (42 to 44 [88%-92%] of 48 patients; P<10(-8)), atovaquone (4 [80%] of 5), eflornithine hydrochloride (40 [57%] of 70; P<.01), trimethoprim-sulfamethoxazole (27 [53%] of 51; P<.08), pentamidine (64 [39%] of 164), and trimetrexate (47 [30%] of 159).. The combination of clindamycin plus primaquine appears to be the most effective alternative treatment for patients with P carinii pneumonia who are unresponsive to conventional antipneumocystis agents.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Clindamycin; Drug Therapy, Combination; Eflornithine; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Salvage Therapy; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.

Topics: Adolescent; Age Factors; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Child; Child, Preschool; Dapsone; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Naphthoquinones; Neoplasms; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The burden of human immunodeficiency virus (HIV)-related disease in sub-Saharan Africa continues to increase; providing adequate care for the huge number of people affected is a daunting task, especially given the limited resources available. Recent studies have shown that low-cost regimens can prevent some of the most important causes of HIV-related disease in African countries. Isoniazid preventive therapy can reduce the incidence of tuberculosis; priorities are to seek opportunities for implementation, to assess effectiveness under operational conditions, and to monitor its effect on resistance patterns. Cotrimoxazole was shown to be highly effective in reducing morbidity and mortality among individuals with symptomatic HIV disease in Côte d'Ivoire, and should be implemented where it is likely to be of benefit. Pneumococcal polysaccharide vaccine was disappointingly ineffective among HIV-infected Ugandan adults, but newer conjugate vaccines are becoming available that should be investigated. The benefit of these preventive regimens to the individual may be modest when compared with the effect of antiretroviral therapy. However, simple preventive therapies could reach a much wider population than is immediately feasible for expensive and complex antiretroviral regimens, and thus have the potential for substantial benefit at the population level. The availability of effective and affordable regimens to prevent HIV-related disease may also encourage people to seek HIV testing, combat denial, and help overcome the sense of powerlessness in countries where the HIV epidemic has hit hardest.

Topics: Adult; Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Humans; Isoniazid; Preventive Health Services; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

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

Tuberculosis is currently an enormous global health problem. In industrialized countries in Western Europe and North America, tuberculosis case rates are low and an increasing proportion of cases now occur in foreign-born individuals and in marginalized populations, including the homeless, prisoners, drug users, and persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). In contrast, the burden of tuberculosis in sub-Saharan Africa continues to grow, largely fueled by the HIV pandemic and poor public health infrastructure. Use of the World Health Organization's (WHO) directly observed therapy, short course (DOTS) strategy has been successful in improving outcomes and preventing the emergence of acquired drug resistance in several African countries; however, case rates are increasing throughout most of the region. It is clear that control of tuberculosis in Africa is closely linked to control of HIV and AIDS. Substantial external donor support and innovative approaches to enhance interactions between HIV/AIDS prevention and treatment efforts and tuberculosis control programs will be needed to improve the current tuberculosis situation in Africa. The purpose of this review is to provide a synopsis of recent developments in these areas and to serve as a reference source for interested readers.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Humans; Incidence; Refugees; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Tuberculosis, Multidrug-Resistant; Western World

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

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Inflammatory Agents; Diagnosis, Differential; Drug Therapy, Combination; Humans; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prednisolone; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell anemia presented to the University of Wisconsin Hospital on two separate occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). Several days into each treatment course he developed hyperkalemia and systemic acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The abnormalities resolved in the first instance with the addition of amphotericin B while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX. While an increasing number of cases with TMP/SMX-induced hyperkalemia have been reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy, occurring in patients with predisposing factors for acidosis such as aldosterone defects, medullary dysfunction and renal insufficiency.

Topics: Acidosis, Renal Tubular; Adult; AIDS-Related Opportunistic Infections; Anemia, Sickle Cell; Anti-Infective Agents; Drug Therapy, Combination; HIV-1; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is one of the leading complications among HIV-infected patients. Recent advances in PCP prophylaxis, diagnosis and treatment have caused a decrease in PCP-related morbidity and mortality. Despite these advances, PCP continues to be frequent in patients not known to be HIV-infected and in those patients with poor adherence to prophylactic regimens or severe immunosuppression. In typical cases diagnosis may be suspected by the patient's clinical presentation. Clinicians are frequently faced with the differential diagnosis between PCP, bacterial pneumonia, pulmonary tuberculosis, and other specific respiratory disorders HIV-associated. Definitive diagnosis of PCP requires demonstration of Pneumocystis carinii (PC) in respiratory secretions or lung tissue. Conventional techniques, immunofluorescence using monoclonal antibodies and molecular techniques are highly specific, but sensitivity varies depending on the PC load present in the sample. Best diagnostic yield is obtained analyzing samples obtained by bronchoalveolar lavage. PC diagnosis using highly sensitive PCR in sputum-induced samples might allow noninvasive diagnosis in most HIV-infected patients suffering from PCP but PCR techniques remain to be standardized. Like in PCP prophylaxis, trimethoprim-sulphametoxazole (TS) is the drug of choice for PCP treatment. In severe case, TS is given intravenously. If patient is intolerant to TS, i.v. pentamidine or i.v. trimetrexate with folinic acid can be used. TS has a dose-dependent toxicity. In cases of hypersensitivity to TS, drug-desensitization should be tried. In severe documented PCP adjunctive corticosteroid therapy is effective and safe. In mild to moderate PCP, TS can be given orally. Best alternatives to TS in this situation are dapsone-pyrimethamine or clindamycin-primaquine (CP). Other effective options are oral atovaquone, aerosolize pentamidine and i.v. pentamidine.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; DNA, Bacterial; Humans; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

The so-called exotic pulmonary mycoses are imported diseases in France. They are infrequent or exceptional and for this reason can be underdiagnosed or recognized with delay. Nevertheless, they are easily treatable infections with available antifungal agents. As a rule, the site of primary infection is the lung with ensuing clearance or chronic local infection and/or dissemination. Immunocompromised hosts are more prone to develop severe forms or reactivation of the disease.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Diagnosis, Differential; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Paracoccidioidomycosis; Penicillium; Sporotrichosis; Sulfadiazine; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

The frequency of Nocardia infection in HIV-infected patients has increased during the past few years from 0.3% in 1985 to 1.8% in 1989. Although it is not of great concern as an AIDS-associated infection, the nonspecific clinical presentation in these patients might be confused with other lung infections such as tuberculosis (TB). The mortality rate can be as high as 60%. The authors diagnosed three homosexual men with nocardiasis among 1060 HIV-infected patients (0.2%) in a tertiary care center in Mexico City from 1981 to 1997. The mean age was 32 years. The CD4 count was less than 260 cells/mm3 in all these individuals. The clinical presentations were subacute sinusitis, chronic localized abdominal abscess, and acute disseminated nocardiasis. The respective associated infections were none; TB and cytomegalovirus (CMV); and candidiasis, TB, CMV, Isospora belli, and disseminated Mycobacterium avium complex (MAC). Trimethoprim/sulfamethoxazole (TMP/SMX) was the treatment in all the cases; at the time of this writing, two patients were living and one had died during the acute episode. A literature search uncovered 130 cases of Nocardia infection in HIV patients since 1982. According to the published data and our results, nocardiasis should be suspected in those HIV-infected patients who (1) do not respond to appropriate antituberculous treatment; (2) are intravenous drug users; and (3) develop a characteristic pericardial infection. Finally, adequate surgical or percutaneous drainage of abscesses are extremely valuable for diagnosis and therapy.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Female; Homosexuality, Male; Humans; Male; Middle Aged; Nocardia Infections; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Since the end of the 1980s, primary anti-Pneumocystis carinii pneumonia (PCP) prophylaxis has become a fundamental part of the global AIDS control strategy in industrialized countries. The widespread adoption of anti-PCP chemoprophylaxis has been a key element in prolonging the survival of patients with AIDS. There is general agreement on the need to begin chemoprophylaxis when individual CD4+ cell counts drop below the value of 200/microL. However, PCP still develops in up to 27% of susceptible HIV-infected patients despite regular prophylaxis intake. Failure of chemoprophylaxis may depend on different factors. The choice of the regimen and the patient's compliance to it have been the first variables to be identified, whereas the importance of the residual cellular immune function as complementary protective mechanism against PCP has emerged in subsequent clinical studies. Albeit of limited general concern, issues such as P. carinii drug resistance and defective drug absorption may play some role in prophylaxis failure in selected patients. Regarding the epidemiology of primary and recurrent episodes of PCP, recent studies based on genetic fingerprinting techniques revealed that interhuman transmission of the organism could be more relevant than so far expected, thus raising some concern of the possibility of nosocomial spread among susceptible individuals. The downgrading tendency of immune competence in HIV infection and the related increasing risk of developing PCP make it possible to envisage a two-step chemoprophylactic strategy, with the most effective compound, cotrimoxazole, to be reserved for the last and most risky disease stage, when immune response no longer provides any support for preventing the development of PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Patient Compliance; Pneumonia, Pneumocystis; Prevalence; Prognosis; Survival Rate; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole remains the treatment of choice in patients with Pneumocystis carinii pneumonia (PCP) requiring intravenous therapy. Those patients who require intravenous therapy who cannot tolerate or who fall therapy with trimethoprim-sulfamethoxazole may be treated with either pentamidine or trimetrexate (plus folinic acid), with or without orally administered dapsone. The toxicity of the former drug makes trimetrexate-based therapy the preferred second choice for parenteral use. Treatment with trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine is approximately of equivalent efficacy, but variable toxicity, in patients with mild to moderate PCP for whom an oral route of administration is appropriate. Atovaquone, formulated as an oral suspension, is also effective, but, in the absence of additional data, must be considered as second line therapy. Adjunctive corticosteroid therapy is indicated for patients with [PAO2-PaO2] more than 30 mm Hg or PaO2 less than 70 mm Hg [corrected] while breathing ambient air in the absence of contraindications. Recognition of the apparent fungal nature of P carinii as well as improved understanding of the pathophysiology of PCP will lead to further improvements in antipneumocystis therapy.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Humans; Infusions, Intravenous; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

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

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Child; Clindamycin; Drug Therapy, Combination; Humans; Pentamidine; Pneumonia, Pneumocystis; Primaquine; 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

Pneumocystis carinii (PC) otitis is a rare opportunistic infection of the acquired immunodeficiency syndrome (AIDS). Initially hearing loss and otalgia occur with thickening of the tympanic membrane and the bordering skin of the ear canal. Otorrhea, ear polyps, perforation of tympanic membrane, destruction of mastoidal bone, and participation of cranial nerves are observed. Diagnosis is established histologically. The treatment of the parasite is by trimethoprim-sulfamethoxazole combinations. The immunological situation seems to be better than in PC pneumonia. Due to the underlying immunological incompetence the infection can not be expected to limit itself. To prevent severe complications as sequestrating mastoiditis, early diagnosis and specific surgical and medical treatment are necessary.

Topics: Adult; AIDS-Related Opportunistic Infections; Combined Modality Therapy; Diagnosis, Differential; Ear, Middle; Humans; Male; Otitis; Otitis Media; Pneumocystis Infections; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood.. A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available.. Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens.. Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.

Topics: AIDS-Related Opportunistic Infections; Dapsone; Dose-Response Relationship, Drug; Humans; Logistic Models; Multivariate Analysis; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Survival Analysis; Toxoplasmosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Adverse cutaneous reactions frequently occur during the treatment of AIDS associated pneumocystosis by trimethoprime-sulfamethoxazole. The most common form is a maculous rash. Treating throughout the duration of hypersensitivity may lead to potentially lethal Stevens-Johnson and Lyell syndromes. Slow acetylator phenotype, a glutathion deficiency and a history of adverse cutaneous reactions have been identified as risk factors of cutaneous reactions. An adjuvant corticosteroid therapy decreases the frequency of adverse cutaneous reactions during the treatment of hypoxaemic pneumocystosis by trimethoprim-sulfamethoxazole.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Eruptions; Humans; Incidence; Pneumonia, Pneumocystis; Risk Factors; Stevens-Johnson Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Incidence; Pneumonia, Pneumocystis; Primary Prevention; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Follow-Up Studies; Humans; Male; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Topics: Age Factors; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Hyperkalemia; Kidney; Pneumonia, Pneumocystis; Potassium; Renal Insufficiency; Risk Factors; 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

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Quality of Health Care; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Child, Preschool; Female; Humans; Infant; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Quality of Health Care; Trimethoprim, Sulfamethoxazole Drug Combination

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Child; Dapsone; Drug Therapy, Combination; Humans; Incidence; Infection Control; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Research; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Toxoplasmic encephalitis (TE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily. HIV-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Cats; Dapsone; Drug Therapy, Combination; Encephalitis; Humans; Incidence; Leucovorin; Pyrimethamine; Recurrence; Risk Factors; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Dapsone; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; 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 treatment and the prevention of Pneumocystis carinii pneumonia (PCP) is based on trimethoprim-sulfamethoxazole. However, hypersensitivity reactions occur often in HIV-infected patients. In this study, clinical and biological parameters of 27 PCP-patients treated by this drug association were analyzed. We divided the drug reactions into two groups according to the severity. A drug reaction occurred in 59.2% of the patients and was note as a mild reaction in 18.5% of the cases and as a severe reaction in 40.7%. An initial high eosinophil count was noted in patients who may present future drug reaction. This difference was more significant in patients who may present severe drug reaction. No other clinical or biological factors were predictive of hypersensitivity. The immune status of HIV-disease, drug therapy, and drug mechanisms were discussed.

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Predictive Value of Tests; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The successful management of nocardial brain abscess remains problematic. The authors report 11 cases of nocardial brain abscess treated between 1971 and 1993 and review 120 cases reported since 1950. The clinical findings included focal deficits in 55 patients (42%), nonfocal findings in 36 (27%), and seizures in 39 (30%). Extraneural nocardiae were present in 66% of the cases; pulmonary (38%) and cutaneous/subcutaneous (20%) locations were the most frequent. The abscesses were single in 54% of the patients, multiple in 38%, and of unknown number in 8%. Forty-four of 131 patients (34%) were immunocompromised; since 1975, 18 of 40 immunocompromised patients (45%) were transplant recipients and six (15%) had human immunodeficiency virus. The mortality rate was 24% after initial craniotomy and excision (11/45), 50% after aspiration/drainage (17/34), and 30% after nonoperative therapy (7/23); 29 cases (22%) were diagnosed at autopsy. The mortality rate was 33% in patients with single abscesses and 66% in those with multiple abscesses (P < 0.0003). There was no difference in the mortality rates of immunocompromised and nonimmunocompromised patients treated before computed tomography (CT) was available; since the advent of CT, however, the mortality rate has been significantly higher in immunocompromised patients (55% vs. 20%, P < 0.05). Although the mortality rate for nocardial brain abscesses has dropped almost 50% since the advent of CT, it has remained virtually unchanged in immunocompromised patients and is three times higher than that of other bacterial brain abscesses (30% vs. 10%). The authors recommend image-directed stereotactic aspiration for diagnosis; however, craniotomy and total excision are necessary in most cases, because nocardial abscesses are usually multiloculated. Patients with minimal neurological deficits or small abscesses may be treated initially with antibiotics alone. Sulfonamides, alone or in combination with trimethoprim, are most effective and should be continued for at least 1 year. Minocycline, imipenem, or aminoglycoside in combination with a third-generation cephalosporin may be used with reasonably good success as second-line agents in cases of allergy or nonresponsiveness to sulfa agents.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Brain Abscess; Combined Modality Therapy; Craniotomy; Drainage; Female; Humans; Male; Middle Aged; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Survival Rate; 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

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Drug Eruptions; Humans; Pneumonia, Pneumocystis; Sulfadiazine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Pneumonia caused by Pneumocystis carinii is the most frequent indication for admission of AIDS patients to intensive care units. In this article, an approach to the diagnosis and management of this condition will be presented along with prognostic information. Differential diagnosis will be discussed, and characteristic responses to current standard and alternative chemotherapeutic agents and modes of ventilatory support will be reviewed.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Diagnosis, Differential; Health Personnel; Humans; Infection Control; Intensive Care Units; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiration, Artificial; Respiratory Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Diagnosis, Differential; Granuloma Inguinale; Humans; Male; Sexually Transmitted Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

The armamentarium of drugs to treat and to prevent Pneumocystis pneumonia has expanded substantially over the past decade. In all patient populations trimethoprim-sulfamethoxazole is the preferred regimen for both acute treatment and prophylaxis. Clindamycin-primaquine and atovaquone are both effective agents for acute therapy but there are no data yet suggesting that they are preferable to trimethoprim-sulfamethoxazole. Corticosteroid therapy is now standard for severe AIDS-associated Pneumocystis pneumonia, and should probably be used in other patient populations with severe pneumocystis pneumonia as well.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Drug Tolerance; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antiprotozoal Agents; Clindamycin; Humans; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

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

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

To assess the effectiveness of Short Message Service (SMS) reminder messages on antiretroviral and cotrimoxazole prophylaxis adherence among HIV-positive youths as well as the relative effectiveness of SMS with and without a response option.. Eligible HIV-positive patients aged 15 to 22 years at 2 HIV clinics in Kampala, Uganda, participated in a year-long parallel individual-randomized controlled trial and were assigned in a 1-to-1-to-1 ratio to a weekly SMS message group, weekly SMS message with response option group, or a usual-care control group.. We enrolled 332 participants. Electronically measured mean adherence was 67% in the control group, 64% in the 1-way SMS group (95% confidence interval [CI] = 0.77, 1.14), and 61% in the 2-way SMS group (95% CI = 0.75, 1.12) in an intent-to-treat analysis. Results for secondary outcomes and complete-case analysis were similarly statistically insignificant across groups.. Despite previous evidence that interventions using SMS reminders can promote antiretroviral therapy adherence, this study shows that they are not always effective in achieving behavior change. More research is needed to find out for whom, and under what conditions, they can be beneficial.. ClinicalTrials.gov identifier: NCT00830622.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Female; HIV Seropositivity; Humans; Intention to Treat Analysis; Male; Medication Adherence; Outcome Assessment, Health Care; Reminder Systems; Text Messaging; 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

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

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

To evaluate the role of prophylactic trimethoprim-sulfamethoxazole (co-trimoxazole) antibacterial prophylaxis in reducing morbidity and mortality in HIV-infected post-natal women in southern Africa.. Double-blind placebo-controlled trial. HIV-infected women with WHO stage 2 or 3 HIV disease who had recently delivered in the Department of Obstetrics and Gynaecology at the University Teaching Hospital, Lusaka, Zambia were randomised to receive daily co-trimoxazole (cotox) or matched placebo daily for the duration of the trial. Participants were followed up for a minimum of 1 year. Primary outcome measures were mortality from any cause or hospital admission and serious adverse events.. Of 600 women randomised, follow-up information was available from 355 (180 cotox, 175 placebo) participants. Thirty-six (17 cotox, 19 placebo) women died during the trial, and another 11 (5 cotox, 6 placebo) were admitted to hospital. There was no significant difference in the combined event rates between the two treatment arms: HR = 0.82, 95% CI (0.46, 1.45), P = 0.49; morbidity was reduced over a range of symptoms. Secondary analyses of the outcome in babies indicated some evidence of reduced mortality in those whose mothers were allocated cotox.. Follow-up rates were poor; there was no evidence that co-trimoxazole prophylaxis reduced mortality or hospital admission rates, although fewer symptoms were reported in the cotox arm. Cotox was safe and well tolerated.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Epidemiologic Methods; Female; Hospitalization; Humans; Medication Adherence; Postnatal Care; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

To investigate whether PALSA PLUS, an on-site educational outreach programme of non-didactic, case based, iterative clinical education of staff, led by a trainer, can increase access to and comprehensiveness of care for patients with HIV/AIDS.. Cluster randomised trial.. Public primary care clinics offering HIV/AIDS care, antiretroviral treatment (ART), tuberculosis care, and ambulatory primary care in Free State province, South Africa.. Fifteen clinics all implementing decentralisation and task shifting were randomised. The clinics cared for 400,000 general primary care patients and 10,136 patients in an HIV/AIDS/ART programme. There were 150 nurses.. On-site outreach education in eight clinics; no such education in seven (control).. Provision of co-trimoxazole prophylaxis among patients referred to the HIV/AIDS/ART programme, and detection of cases of tuberculosis among those in the programme. Proportion of patients in the programme enrolled through general primary care consultations.. Patients referred to the HIV/AIDS programme through general primary care at intervention clinics were more likely than those at control clinics to receive co-trimoxazole prophylaxis (41%, (2253/5523) v 32% (1340/4210); odds ratio 1.95, 95% confidence interval 1.11 to 3.40), and tuberculosis was more likely to be diagnosed among patients with HIV/AIDS/ART (7% (417/5793) v 6% (245/4343); 1.25, 1.01 to 1.55). Enrolment in the HIV/AIDS and ART programme through HIV testing in general primary care was not significantly increased (53% v 50%; 1.19, 0.51 to 2.77). Secondary outcomes were similar, except for weight gain, which was higher in the intervention group (2.3 kg v 1.9 kg, P<0.001).. Though outreach education is an effective and feasible strategy for improving comprehensiveness of care and wellbeing of patients with HIV/AIDS, there is no evidence that it increases access to the ART programme. It is now being widely implemented in South Africa.. Current Controlled Trials ISRCTN 24820584.

Topics: Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Anti-HIV Agents; Anti-Infective Agents; Cluster Analysis; Female; Health Personnel; Humans; Male; Microbiology; Primary Health Care; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

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

The study aims to evaluate the efficacy of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) lung clearance test in the diagnosis of pneumocystis carinii pneumonia (PCP) in HIV-positive paediatric patients. Twenty HIV-negative patients with no chest symptoms constituted Group A, 25 HIV antibody positive asymptomatic children formed Group B, while 45 HIV antibody positive children with respiratory infections comprised Group C. Group C was subdivided into C(1) (n = 20, documented PCP on microbiology), C(2) (n = 10, tuberculosis) and C(3) (n = 15, bacterial pneumonias). The mean age group of patients in Group A, Group B and Group C was 4.7 +/- 1.9, 4.2 +/- 1.5 and 4.8 +/- 1.7 years, respectively. All patients were subjected to complete blood count, blood culture, chest radiographs, microscopic staining of sputum (PCP stains, Ziehl-Nielsen staining, Gram staining), ABG and Mantoux test. All these patients underwent dynamic lung scans using (99m)Tc-DTPA aerosols and lung clearance was calculated in terms of half-time transfer value (T(1/2)) value. T(1/2) was compared between different groups and lung scan findings were correlated with radiological and microbiological results. Patients with PCP had T(1/2) in the range of 9.02 +/- 1.35, TB 28.2 +/- 3.03 min and other bacterial pneumonias in the range of 20.5 +/- 3.1 min (range for normal individuals was 49.8 +/- 6.13 min). T(1/2) in patients with PCP was found to be significantly lower when compared with T(1/2) in other groups. Patients with PCP had characteristic biphasic curves while the rest had monophasic curves. Some patients with PCP had low T(1/2) values even when chest radiographs and arterial blood gases were normal. (99m)Tc-DTPA lung clearance test is a sensitive, safe and non-invasive diagnostic tool for the early detection of PCP in HIV-positive paediatric patients.

Topics: Administration, Inhalation; Aerosols; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Female; HIV Seropositivity; HIV-1; Humans; Lung; Male; Pneumonia, Pneumocystis; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Pentetate; Trimethoprim, Sulfamethoxazole Drug Combination

This article presents data from an AIDS clinical trial that evaluated 238 (60 percent nonwhite) patients infected with HIV and their clinician's perceptions of medication adherence and visit attendance in relationship to lifestyle, psychosocial, and health belief model (HBM) variables. Twelve sites collected data via a prospective, multisite observational study design involving a companion study to a larger randomized clinical trial. Baseline information was collected by questionnaire and patient self-report on lifestyle; work and health-care experiences; available support; and psychosocial issues, including the HBM constructs. At follow-up visits, clinicians and patients graded medication adherence using the same scale. Patients confidentially reported follow-up information about lifestyle and answered HBM questions. After 12 months, adherence with study visits was associated with older age. Clinicians rated patients as having good adherence significantly more often when those patients were older, were employed at the time of enrollment, exhibited altruism as part of the reason for enrolling in the clinical trial, and thought HIV was very serious. Patients rated themselves as having good adherence significantly more often if they were older, had family or friends who were infected with HIV, and believed that being in the study was worth the trouble.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Data Collection; Humans; Logistic Models; Middle Aged; Patient Compliance; Pneumonia, Pneumocystis; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In the CHAP randomized placebo-controlled trial of cotrimoxazole prophylaxis in HIV-infected Zambian children conducted between 2001 and 2003, cotrimoxazole was associated with significant mortality reductions. In a secondary analysis we used Cox regression models to estimate the association between adherence measured by bottle weights and caregiver report and subsequent mortality in children surviving >28 days (n = 496, 153 deaths). Adherence was high and similar in both cotrimoxazole and placebo groups; adherence from bottle weights was 100% at 71% of visits, while caregivers reported 100% adherence at 79% of visits. Every 10% lower adherence to cotrimoxazole or placebo measured by bottle weights was associated with a 10-11% increase in mortality risk. Effects remained after adjustment for baseline predictors of survival and for current and recent change in primary caregiver. Caregiver-reported adherence was not associated with survival. The association between bottle-weight adherence to placebo and survival is likely capturing unmeasured caregiver effects, whose identification will be essential for quantifying the impact of antiretroviral therapy (ART) adherence on clinical outcomes in children.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Caregivers; Child; Child, Preschool; Humans; Infant; Medication Adherence; Pneumonia, Pneumocystis; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

Recently, Plasmodium falciparum bearing dihydrofolate reductase (DHFR) I164L was isolated from Africa. Quadruple mutations containing I164L confer high-level resistance to antifolate antimalarials. We prospectively measured the effect of co-trimoxazole (CTX) prophylaxis on P. falciparum antifolate resistance development among HIV-infected persons. HIV-positive patients with CD4 cell count < 350 cells/microl (n=692) received CTX; HIV-positive patients with CD4 cell count > or = 350 cells/microl (n=336) and HIV-negative patients (n=132) received multivitamins. Malaria microscopy-positive samples (n=413) and selected microscopy-negative/PCR-positive samples (n=76) were analysed for DHFR mutations at baseline and during six months follow up. We identified I164L in 14 patients. Seven were malaria microscopy-positive: two failed sulfadoxine-pyrimethamine (SP). Among seven microscopy-negative/PCR-positive patients, none developed patent infections with I164L. I164L was not associated with high-level SP resistance or poor outcome among adults living where malaria is highly endemic. Surveillance to monitor spread of I164L is critical, especially among children and pregnant women, who are potentially a source for I164L amplification.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Animals; Antimalarials; CD4 Lymphocyte Count; Drug Combinations; Drug Resistance; Female; Humans; Malaria, Falciparum; Male; Middle Aged; Mutation; Plasmodium falciparum; Prospective Studies; Pyrimethamine; Sulfadoxine; Tetrahydrofolate Dehydrogenase; Treatment Outcome; 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

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

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In 2000, WHO/UNAIDS recommended co-trimoxazole prophylaxis for persons at early stages of HIV infection (WHO stage > or = 2) in sub-Saharan Africa.. To assess the cost-effectiveness of alternative strategies for initiation of co-trimoxazole in Côte d'Ivoire.. Cost-effectiveness analysis with an HIV simulation model using clinical and cost data from a randomized trial of co-trimoxazole in HIV-infected adults.. The study included HIV-infected patients in Côte d'Ivoire, with median age 33 years. Thirty-four percent were classified as WHO stage 2, 59% as stage 3, and 7% as stage 4. The mean CD4 cell count was 331 x 10(6) cells/l. The interventions were no prophylaxis, clinical criteria-based co-trimoxazole initiation (early: WHO stage > or = 2; late: WHO stage > or = 3), CD4-based co-trimoxazole initiation (< 500, < 200, < 50 x 10(6) CD4 cells/l). The outcome measures were life expectancy, lifetime costs, and incremental cost-effectiveness.. The most effective strategy, initiation of co-trimoxazole prophylaxis at WHO stage > or = 2, increased undiscounted life expectancy by 5.2 months, discounted life expectancy by 4.4 months, and lifetime costs by US dollars 60, compared with no prophylaxis. Delaying prophylaxis initiation until WHO stage >or = 3 was less costly and less effective. All CD4-based strategies were dominated. The incremental cost-effectiveness of early versus late co-trimoxazole prophylaxis initiation was US dollars 200/year of life gained. Results were stable despite wide variations in plausible assumptions about bacterial resistance and the prophylaxis efficacy on co-trimoxazole-resistant strains.. For HIV-infected adults in Côte d'Ivoire, co-trimoxazole prophylaxis is reasonably cost-effective and most effective if initiated when WHO stage > or = 2. Early co-trimoxazole prophylaxis will prevent complications prior to antiretroviral therapy initiation and should be considered an essential component of care for early HIV in sub-Saharan Africa.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cost-Benefit Analysis; Drug Resistance, Viral; Female; Humans; Length of Stay; Life Expectancy; Male; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Prospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

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

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient.. Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides.. AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75 mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD(4)/CD(8) counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months.. Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD(4) counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD(8) counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed.. Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4-CD8 Ratio; Desensitization, Immunologic; Drug Administration Schedule; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pilot Projects; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

We compared the occurrences of several types of infections in HIV-infected patients participating in a randomized clinical trial of three treatment strategies given for the primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis. In a phase III open label trial, 842 patients with HIV infection and fewer than 200 CD4+ cells/mm(3) received zidovudine (standard dose) plus one of three randomly assigned prophylactic agents: trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone (DAP), or aerosolized pentamidine (AP). Patients developing intolerance to treatment were crossed over to another predefined prophylactic therapy. Patients were monitored for infections every other week for 8 weeks and then monthly until the study was completed. Primary statistical models were proportional hazards models adapted to recurrent end points. In an intent-to-treat analysis, compared with AP and DAP, TMP-SMZ significantly reduced the risk of any bacterial infection (combining all distinct types) (p = 0.02 and p = 0.01, respectively). When considering distinct types separately, compared with AP, TMP-SMZ significantly reduced the risk of infectious diarrhea (p = 0.04); compared with DAP, AP and TMP-SMZ significantly reduced the risk of sinusitis/otitis media (p = 0.03 and p = 0.04, respectively); compared with AP and DAP, TMP-SMZ significantly reduced the risk of a second occurrence of pneumonia (p = 0.04 and 0.02, respectively). For any bacterial infection, infection rates per 100 patient-years of follow-up were 31, 39, and 38 for TMP-SMZ, DAP, and AP, respectively. In patients with advanced HIV infection not taking highly active antiretroviral therapy, the treatment strategy that initiates prophylaxis with TMP-SMZ is superior to those initiating with AP or DAP for preventing any bacterial infection, with most of the advantage manifested through infectious diarrhea, sinusitis/otitis media, and pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bacterial Infections; Female; Humans; Male; Regression Analysis; 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 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

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

In developing countries, Isospora belli and Cyclospora cayetanensis frequently cause chronic diarrhea in HIV-infected patients.. To compare 1 week of trimethoprim-sulfamethoxazole treatment and 1 week of ciprofloxacin treatment in HIV-infected patients with chronic diarrhea caused by I. belli and C. cayetanensis.. Randomized, controlled trial.. HIV clinic in Port-au-Prince, Haiti.. 42 HIV-infected patients with chronic diarrhea due to I. belli (n = 22) or C cayetanensis (n = 20).. Patients were randomly assigned to receive oral trimethoprim-sulfamethoxazole (160 mg or 800 mg) or ciprofloxacin (500 mg) twice daily for 7 days. Patients who responded clinically and microbiologically received prophylaxis for 10 weeks (1 tablet orally, three times per week).. Treatment success was measured by cessation of diarrhea and negative stool examination at day 7. Prophylaxis success was measured by recurrent disease rate.. Diarrhea ceased in all 19 patients treated with trimethoprim-sulfamethoxazole. Eighteen of 19 patients had negative results on stool examination at day 7 (95%). Among the 23 patients who received ciprofloxacin, diarrhea ceased in 20 (87% [CI; 66% to 97%]) and 16 had negative results on stool examination at day 7 (70%). By survival analysis, diarrhea from isosporiasis and cyclosporiasis ceased more rapidly with trimethoprim-sulfamethoxazole than with ciprofloxacin. All patients receiving secondary prophylaxis with trimethoprim-sulfamethoxazole remained disease-free, and 15 of 16 patients receiving secondary prophylaxis with ciprofloxacin remained disease-free.. A 1-week course of trimethoprim-sulfamethoxazole is effective in HIV-infected patients with cyclosporiasis or isosporiasis. Although ciprofloxacin is not as effective, it is acceptable for patients who cannot tolerate trimethoprim-sulfamethoxazole.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Chronic Disease; Ciprofloxacin; Coccidiosis; Diarrhea; Drug Administration Schedule; Eucoccidiida; Humans; Isospora; Middle Aged; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

AIDS Clinical Trial Group (ACTG) randomized trial 021 compared the effect of bactrim versus aerosolized pentamidine (AP) as prophylaxis therapy for pneumocystis pneumonia (PCP) in AIDS patients. Although patients randomized to the bactrim arm experienced a significant delay in time to PCP, the survival experience in the two arms was not significantly different (p = .32). In this paper, we present evidence that bactrim therapy improves survival but that the standard intent-to-treat comparison failed to detect this survival advantage because a large fraction of the subjects either crossed over to the other therapy or stopped therapy altogether. We obtain our evidence of a beneficial bactrim effect on survival by artificially regarding the subjects as dependently censored at the first time the subject either stops or switches therapy; we then analyze the data with the inverse probability of censoring weighted Kaplan-Meier and Cox partial likelihood estimators of Robins (1993, Proceedings of the Biopharmaceutical Section, American Statistical Association, pp. 24-33) that adjust for dependent censoring by utilizing data collected on time-dependent prognostic factors.

Topics: Acquired Immunodeficiency Syndrome; Aerosols; AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Biometry; Humans; Models, Statistical; Multicenter Studies as Topic; Pentamidine; Pneumonia, Pneumocystis; Probability; Randomized Controlled Trials as Topic; Reproducibility of Results; Survival Rate; Treatment Refusal; 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

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

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

We enrolled 2,625 human immunodeficiency virus-infected patients into a randomized trial to assess the efficacy and tolerability of daily vs. thrice-weekly trimethoprim-sulfamethoxazole (160 mg/800 mg) for prophylaxis of Pneumocystis carinii pneumonia (PCP). The rate of PCP was 3.5 and 4.1 per 100 person-years in the daily and thrice-weekly groups, respectively, with a relative risk (RR) of 0.82 (95% confidence interval [CI], 0.61-1.09; P = .16) (RR of <1.0 favors daily trimethoprim-sulfamethoxazole). The RR for PCP determined by on-treatment analysis was 0.59 (P = .03). The RR for death was 0.91 (P = .12); for bacterial pneumonia, 0.82 (P = .06); and for combined PCP and bacterial pneumonia, 0.84 (P = .04). Discontinuation due to adverse events occurred more commonly in the daily trimethoprim-sulfamethoxazole group (RR, 2.14; 95% CI, 1.73-2.66; P < .001). Overall estimates for efficacy end points favored daily trimethoprim-sulfamethoxazole, although rates of intolerance were higher among patients receiving that dose. Daily trimethoprim-sulfamethoxazole may offer advantages as a first choice for PCP prophylaxis; thrice-weekly dosing is an appropriate option for patients intolerant of the daily dose.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).. Open-label, nonrandomized study.. Two clinical research centers.. Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm3.. Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX).. Average steady-state atovaquone concentrations at 500 mg were 6.7 +/- 3.2 microg/ml fasted and 11.3 +/- 5.0 microg/ml with food; at 750 mg, 9.9 +/- 7.1 microg/ml fasted and 12.5 +/- 5.9 microg/ml with food; at 1000 mg, 9.7 +/- 4.3 microg/ml fasted and 13.6 +/- 5.0 microg/ml with food; and at 1500 mg, 21.1 +/- 5.0 microg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 microg/ml in 21% and more than 15 microg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 microg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Fasting; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Double-Blind Method; Humans; Pneumonia, Pneumocystis; Senegal; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Encephalitis; Female; Humans; Male; Pilot Projects; Prospective Studies; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

This double-blind, randomized, multicenter trial compared clindamycin/primaquine (Cm/Prq) with trimethoprim-sulfamethoxazole (TMP-SMZ) as therapy for AIDS-related Pneumocystis carinii pneumonia (PCP). Forty-five patients received clindamycin (450 mg four times daily [q.i.d.]) and primaquine (15 mg of base/d); 42 received TMP-SMZ (320 mg/1,600 mg q.i.d. if weight of > or = 60 kg or 240 mg/1,200 mg q.i.d. if weight of < 60 kg) plus placebo primaquine. Overall, the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 76% vs. 79%, respectively); Cm/Prq was associated with fewer adverse events (P = .04), less steroid use (P = .18), and more rashes (P = .07). These differences were even greater for patients with PaO2 of > 70 mm Hg (P = .02, P = .04, and P = .02, respectively). For patients with PaO2 of < or = 70 mm Hg (23 Cm/Prq recipients and 21 TMP-SMZ recipients), the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 74% vs. 76%, respectively); Cm/Prq was associated with similar adverse events (P = .57), steroid use (P = .74), and rashes (P = .78). This trial confirms that Cm/Prq is a reasonable alternative therapy for mild and moderately severe PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Non-viral opportunistic infections involving the central nervous system in AIDS patients most commonly result from toxoplasmic encephalitis (TE). Combination pyremethamin (pyr)/sulfadiazine (sulf) is the mainstay treatment for TE, but many patients experience severe adverse events occasionally requiring discontinuation of this antitoxoplasmic medication. This investigation assessed the effects of an open, prospective trial of alternative trimethroprim/sulfamethoxazole: cotrimoxazole (CTX) therapy for TE in AIDS patients.. The subjects were 18 AIDS patients with a first presumptive attack of TE (Group 1) and 9 relapsing patients, including 6 out of Group 1 (Group 2). We gave CTX as a therapy at the dose of 960 mg four times a day for 48 hours, then 960 mg three times a day for two weeks, followed by 960 mg twice daily until computed tomography showed complete disappearance of active TE lesions. Life-long maintenance therapy consisted to CTX 960 mg daily.. Group 1: Seventeen patients improved clinically and achieved complete resolution on computed tomography scars over a mean period of 33 days (range: 21-56). Only one patient was withdrawn from the study at day 18 due to a severe skin rash. Neither serious hematologic nor liver toxicity were observed. Under maintenance therapy, 7 patients relapsed after an average duration of 15.5 months. Relapses were precipitated either by poor compliance (5/7) or erronenous CTX protocol (2/7). Group 2: There were 15 relapses affecting 9 patients who were treated successfully with CTX. CTX was discontinued in one relapsing patient who experienced a Stevens-Johnson syndrome on day 13. This patient had previously experienced cutaneous intolerance to sulfadiazine.. A relative low dose regimen of CTX appears to be strongly efficient and safe treatment for toxoplasmic encephalitis in AIDS. Such a study is of particular interest for developing countries where TE is highly prevalent, given the wide availability of CTX which could be proposed as an economic first line therapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Female; HIV Seropositivity; Humans; Male; Middle Aged; Patient Selection; Recurrence; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; 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

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

In a randomized double blind placebo controlled trial, HIV sero-positive patients with CD4+ cell count less than 200 x 10(6)/l or an AIDS diagnosis were evaluated for drug reactions to trimethoprim-sulphamethoxazole (TMP-SMX) during treatment, including pretreatment, with N-acetylcysteine (NAC) 800 mg daily or placebo. TMP-SMX (one double-strength tablet containing 160 mg of trimethoprim and 800 mg of sulphamethoxazole) was given three times weekly as primary Pneumocystis carinii (PCP) prophylaxis. Thirty percent (n = 15) of the patients experienced adverse reactions 8-20 (mean 12.7) days after starting with TMP-SMX. At entry, low cysteine and glutathione levels in plasma were found in the HIV-positive patients. Age, sex, CD4+ count, plasma cysteine and glutathione levels were not risk factors for adverse reactions to TMP-SMX. However, concomitant therapy with nucleoside analogues was associated with increased risk for TMP-SMX reactions. Oral NAC 800 mg daily was well tolerated, but replenished neither cysteine nor glutathione levels in plasma. NAC 800 mg/day did not significantly decrease the risk of adverse reactions to TMP-SMX in this study, and could thus not be recommended for this purpose. A prolonged pretreatment period and/or higher dose of NAC may be necessary for clinical effect.

Topics: Acetylcysteine; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cysteine; Exanthema; Female; Fever; Glutathione; Humans; Male; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Injections, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Dapsone; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.. A randomized, double-blind study.. 24 U.S. academic medical centers.. 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less.. Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone.. Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions.. No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01).. The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Dapsone; Double-Blind Method; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Prospective Studies; Quality of Life; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60 percent) and good in 38 (27 percent) children. All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7 percent of the 60-mg treatments and in 19.1, 6. 1, and 2.8 percent of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20). AP can be safely administered to very young children with few adverse side effects.

Topics: Adolescent; Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Tolerance; Female; Humans; Infant; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Safety; Trimethoprim, Sulfamethoxazole Drug Combination

We randomized 220 HIV-1-infected subjects to receive aerosolized pentamidine (300 mg/4 weeks) or orally trimethoprim-sulfamethoxazole (320-1600 mg/day) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), and evaluated PCP and toxoplasmic encephalitis (TE) occurrence and survival. Patients developing toxicity switched to the other regimen. Analysis was on intention-to-treat. At 1 year of study, we observed in the pentamidine group a non-significant excess of PCP (4 vs. 1) and TE (7 vs. 3), and a significant increased death rate (15 vs. 2). After 2 years, no significant differences were observed: adjusted RR estimates for pentamidine vs. cotrimoxazole were 1.20 (95% CI, 0.33-4.37) for PCP (6 cases vs. 5), 1.23 (95% CI, 0.46-3.29) for TE (10 vs. 8) and 1.52 (95% CI, 0.83-2.79) for death (30 vs. 18). Crossovers were more frequent in the cotrimoxazole group (41 vs. 4, P < 0.001). Aerosolized pentamidine and cotrimoxazole were equally effective in preventing PCP, and no major differences were observed in TE occurrence and survival after 2 years follow-up.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; HIV-1; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To establish whether an outpatient, 2-day oral desensitization protocol would be both safe and effective in HIV-infected patients with previous trimethoprim-sulfamethoxazole (TMP-SMX) intolerance.. A single center trial of TMP-SMX desensitization in HIV-infected patients with prior TMP-SMX hypersensitivity reactions.. HIV-infected patients with CD4 lymphocyte counts < 250 x 10(6)/l cells or CD4% < 20% with previous non-life-threatening hypersensitivity reactions to TMP-SMX were eligible. The desensitization protocol utilized 40 graduated doses over 36 h; the first 28 doses (7.5 h) of the protocol were given in an outpatient clinic with the remaining doses taken at home.. Twenty-seven (60%) of the 45 subjects completed the protocol and were subsequently maintained on daily TMP-SMX without adverse reactions (mean follow-up, 9 months; range, 4-16 months). Patients with CD4 counts < 100 x 10(6)/l cells were just as likely as patients with higher CD4 counts to tolerate the desensitization. No patient required hospitalization for treatment of an adverse reaction.. Oral desensitization to TMP-SMX in HIV-infected patients is a useful option in the management of patients with advanced HIV disease and prior intolerance to TMP-SMX.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Drug Hypersensitivity; Drug Tolerance; Humans; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = -3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo. follow-up there was no difference in mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; AIDS-Related Opportunistic Infections; Double-Blind Method; Female; Humans; Male; Oxygen; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy and safety of two oral, intermittent drug regimens for the simultaneous primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with HIV infection.. Nonblinded randomized study: Patients received either 1) trimethoprim-sulfamethoxazole (160 mg-800 mg orally twice a day on a thrice weekly regimen) or 2) 100 mg of dapsone plus 50 mg of pyrimethamine orally twice weekly.. University teaching hospital in Barcelona.. 230 patients infected with HIV who had CD4 cell counts of less than 200 x 10(6)/L and who had not previously had P. carinii pneumonia or toxoplasmosis.. Clinical and biological evaluations; adverse reactions; and end points of P. carinii pneumonia, toxoplasmosis, and death.. After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients receiving trimethoprim-sulfamethoxazole developed P. carinii pneumonia (P < 0.0001). The cumulative rates of P. carinii pneumonia at 12 and 24 months were 0% and 0% for patients receiving trimethoprim-sulfamethoxazole and 4% and 11% for patients receiving dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only one episode of P. carinii pneumonia developed while patients were taking these drugs. No differences were observed for toxoplasmosis (one episode in the trimethoprim-sulfamethoxazole arm and two in the dapsone-pyrimethamine arm), with cumulative rates at 12 and 24 months of 0% and 4% for the trimethoprim-sulfamethoxazole arm and 2% and 7% for the dapsone-pyrimethamine arm (P = 0.65). Similar mortality rates were observed during follow-up (P = 0.85). Nineteen patients (9.5%) discontinued therapy with the drugs because of adverse effects: Ten were in the trimethoprim-sulfamethoxazole arm and 9 were in the dapsone-pyrimethamine arm (P = 0.95).. Thrice-weekly trimethoprim-sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous primary prophylaxis of P. carinii pneumonia and toxoplasmosis in patients infected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a safe and effective alternative.

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

Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Female; HIV-1; Humans; Male; Middle Aged; Prospective Studies; 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

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

We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV).. In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance.. The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent.. In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.

Topics: Administration, Oral; Adult; Aerosols; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Dapsone; Drug Tolerance; Female; Humans; Male; Patient Compliance; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

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

In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP) against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94 patients participated in the study, 47 in each group. The patients were observed for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while 1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was 9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX-TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX-TMP. Furthermore, we found a tendency towards a protective effect against toxoplasmosis in the SMX-TMP group, though there was no difference in survival between the two groups. There was no statistical difference in frequency of crossover from one therapy form to the other. Based on these data we recommend SMX-TMP for secondary PCP prophylaxis.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Premedication; Prospective Studies; Recurrence; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical presentation, radiological and laboratory evaluation, treatment, and risk factors of sinusitis in a cohort of 376 human immunodeficiency virus (HIV)-infected children from a placebo-controlled clinical trial of intravenous immunoglobulin (IVIG) as prophylaxis for infections were examined. Ninety-five episodes of sinusitis were described in 60 patients; one-third of the patients had two or more episodes. Sinusitis episodes were commonly associated with nonspecific, chronic symptoms (67.4%, persistent nasal discharge; 54.7%, nocturnal or persistent cough), whereas symptoms more specific to acute sinusitis were less frequent (17.9%, headache or facial pain; 9.5%, periorbital swelling; 25.3%, temperature of > or = 102 degrees F; 9%, total white blood cell count of > or = 15,000/mm3). The sinuses primarily involved were the maxillary sinus (85.9%) and the ethmoidal sinus (42.3%); 36% of episodes involved two or more sinuses. Preceding respiratory infections did not appear to increase the risk of sinusitis, and CD4+ lymphocyte counts in children with and without sinusitis did not differ. Neither monthly IVIG prophylaxis nor three times weekly trimethoprimsulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia decreased the risk of sinusitis. Sinusitis in HIV-infected children is most often subacute and recurrent. Evaluations of new modalities for prophylaxis for sinusitis are needed.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Female; Humans; Immunoglobulins, Intravenous; Infant; Male; Recurrence; Risk Factors; Sinusitis; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

Topics: Adolescent; Adult; AIDS-Related Complex; AIDS-Related Opportunistic Infections; Antifungal Agents; Female; Humans; Male; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.. Randomized, open label, prospective trial.. A single Infectious Diseases Department in Italy.. HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE.. Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).. PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.. Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.. Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Dapsone; Encephalitis; Female; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Humans; Incidence; Leucovorin; Male; Middle Aged; Neutropenia; Placebos; Pneumonia, Pneumocystis; Probability; Risk Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

We retrospectively studied all courses of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) alone and with adjuvant corticosteroids for AIDS-associated Pneumocystis carinii pneumonia. The corticosteroids were administered for 8-21 days (mean, 14 days) because of hypoxemia. We evaluated the influence of corticosteroids on the incidence of cutaneous adverse reactions to TMP-SMZ and on the course of AIDS during 3 months of follow-up. Of 38 patients treated with TMP-SMZ alone, 18 (47%) developed cutaneous side effects, whereas three (13%) of the 23 patients who received adjuvant corticosteroid therapy experienced such effects (P = .014). Of the 21 reactive patients, 14 were treated throughout the duration of hypersensitivity. Therapy was interrupted for seven patients (18%) treated with TMP-SMZ alone and for none of those who were given adjuvant corticosteroid therapy (P = .23). During follow-up, the incidence of mucocutaneous herpes simplex virus infection was higher among patients who received adjuvant corticosteroids than among those treated with TMP-SMZ alone (P = .005). Adjuvant corticosteroids thus reduce the incidence of adverse cutaneous reactions to TMP-SMZ in patients with AIDS who are treated for hypoxemic P. carinii pneumonia.

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfalene; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We measured the urine concentrations of sulfamethoxazole, sulfamethoxazole hydroxylamine, and N-sulfamethoxazole on days 3 and 10 in 15 patients with acquired immunodeficiency syndrome treated with a combination product of trimethoprim (15 mg/kg/day) and sulfamethoxazole (75 mg/kg/day). The percentage of sulfamethoxazole and metabolites excreted on days 3 and 10, respectively, were sulfamethoxazole 17.2% +/- 11.3% versus 15.6% +/- 8.2%; sulfamethoxazole hydroxylamine 2.6% +/- 2.0% versus 5.0% +/- 5.2% (p < 0.05); N-acetylsulfamethoxazole 80.0% +/- 12.9% versus 79.8% +/- 11.8%. The percentage of sulfamethoxazole hydroxylamine excreted was similar between the eight patients who discontinued therapy because of toxicity and the seven patients who did not (2.9% +/- 2.3% versus 2.3% +/- 2.0%, p = 0.7). In two patients who had major liver toxicity the percentage of sulfamethoxazole hydroxylamine excreted was significantly lower than that of the 13 patients who did not (0.8% +/- 0.1% versus 2.9% +/- 2.0%, p < 0.05). This is the first report of the formation and excretion of sulfamethoxazole hydroxylamine in patients with acquired immunodeficiency syndrome. With 15 patients we were unable to show a significant correlation between the percentage of sulfamethoxazole hydroxylamine excreted and adverse reactions. However, patients with liver toxicity excreted less sulfamethoxazole hydroxylamine.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Pneumonia, Pneumocystis; Sulfamethoxazole; 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

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

The effectiveness and tolerability of Sulfamethoxazole with Trimethoprim (SMX-TMP), a dose of 400mg/80mg given twice a day as secondary prophylaxis (SP) against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 166 AIDS patients. The mean observation period was 9.7 months (range 1.0-1.4). Relapse of PCP occurred in eight patients; four episodes were histologically verified and four episodes were clinically assumed. The relapse rate after one year of prophylaxis was 5.1% (95% CI 0.0%-11.0%) using the log-rank test. Intolerance of secondary prophylaxis, defined as adverse effects necessitating cessation of SP with SMX-TMP, was reported in eight patients (5%) (95% CI 2.1%-9.3%).

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group). All patients were treated with co-trimoxazole. In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the PIIINP levels decreased while steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS prevents this increased inflammatory activity.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Methylprednisolone; Middle Aged; Peptide Fragments; Pneumonia, Pneumocystis; Procollagen; Prognosis; Pulmonary Gas Exchange; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this double-blind pilot trial was to compare clindamycin/primaquine with trimethoprim-sulfamethoxazole (TMP-SMZ) as primary treatment for AIDS-related Pneumocystis carinii pneumonia (PCP). The focus was on toxicity and tolerability since comparisons of efficacy were limited by the small sample size. Sixty-five individuals with a first episode of possible PCP were randomly assigned to receive clindamycin/primaquine (34 patients) or TMP-SMZ (31 patients). PCP was subsequently proven microbiologically in 27 and 22 of the patients in these respective groups. Half of the participants had an arterial partial oxygen pressure at enrollment of < or = torr. The incidence and severity of adverse reactions were lower--but not significantly lower (P = .07 and .08, respectively)--with clindamycin/primaquine. The markers of severity improved in a similar manner regardless of which regimen was administered. No significant differences were documented in outcome, duration of survival, length of the PCP-free interval, or rate of relapse. The results of this pilot study show a trend toward less toxicity with clindamycin/primaquine than with TMP-SMZ. This result must be confirmed by larger-scale clinical trials, which are also needed to better compare the efficacy of the two regimens.

Topics: Adult; AIDS-Related Opportunistic Infections; Clindamycin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Pneumonia, Pneumocystis; Primaquine; Recurrence; 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 whether combined chemotherapy with tinidazole, thiabendazole and cotrimoxazole is more effective than placebo in treatment of AIDS diarrhoea in Zambia.. Single-blind prospective comparison in consecutive patients, randomized alternately to placebo or chemotherapy.. A district hospital in Zambia.. Sixty-four HIV-seropositive patients with chronic diarrhoea were considered for inclusion in the study. Of these, 25 patients were not eligible for randomization (in 13 cases because of spontaneous remission); 11 were randomized, but excluded from the analysis (seven failed to attend for a scheduled visit and four died), leaving 28 patients who completed the study.. Proportion of diarrhoea-free days in the 7 days following treatment, as determined by daily stool counts.. There were 38 diarrhoea-free days out of 89 (43%) in the placebo group, and 39 out of 72 (54%) in the chemotherapy group; this difference was not statistically significant.. The high level of spontaneous remission probably indicates a natural fluctuation in stool frequency and demonstrates the need for placebo-controlled studies in any assessment of therapy for AIDS diarrhoea. Our findings do not allow us to conclude that the chemotherapy used is ineffective, since the number of patients was low, but will help in our understanding of the natural history of the disorder and the design of future studies.. One of the principal features of AIDS in Africa is the diarrhea wasting syndrome known as "slim disease." Although several researchers have tried to identify the pathogens implicated in diarrhea, none can be found in a large proportion of cases. Treatment regimens must be particularly effective in Africa, a region with many competing demands upon the drug budget. In this context, the authors compared the effects of a placebo against the effects of a drug regimen against diarrhea in 28 HIV-seropositive patients with chronic diarrhea. The regimen of combined chemotherapy with tinidazole, thiabendazole, and cotrimoxazole would be expected to eradicate or substantially many of the pathogens most frequently implicated in such cases. There were 38 diarrhea-free days out of 89 in the placebo group and 39 out of 72 in the chemotherapy group; a difference which was not statistically significant. The high level of spontaneous remission observed in this study most likely indicates a natural fluctuation in stool frequency and demonstrates the need for placebo-controlled studies in any assessment of therapy for AIDS diarrhea. The authors stress that the small number of patients involved in the study precludes them from ruling that the combined chemotherapy is ineffective.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Diarrhea; Drug Therapy, Combination; Humans; Thiabendazole; Tinidazole; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

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

Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii.. We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg).. Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group.. For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Confidence Intervals; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Odds Ratio; Pneumonia, Pneumocystis; Regression Analysis; 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

Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown.. We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis.. After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02).. For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.

Topics: Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leukocyte Count; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Standard treatments of HIV-associated Pneumocystis carinii pneumonia (PCP) consist of high dose intravenous or oral cotrimoxazole or intravenous pentamidine. Both treatment modalities are associated with a high incidence of side effects which strengthen the need for alternative therapies. Since April 1987 we have used the combination of dapsone plus trimethoprim (DP+TMP) as primary treatment for PCP in patients who could be managed on an outpatient basis. We report the results of an analysis of the efficacy and toxicity of this treatment in 20 episodes of PCP in 18 patients. PCP was diagnosed by identification of the pathogens in bronchoalveolar lavage specimens. Chest X-ray revealed bilateral involvement in 11 and unilateral in 7 cases and no infiltration in one patient. Treatment over three to four weeks was successful in 14 of 20 PCPs (70%). In six cases (30%) treatment was changed to another regimen after a mean of seven days due to a maculopapular rash (n = 2), haematotoxic side effects (n = 2), persistent fever (n = 1) and for unexplained reasons (n = 1). Less severe side effects not causing a change in treatment were a slight to moderate neutropenia (n = 10), a moderate elevation of liver enzymes (n = 2) and a well tolerated rash (n = 2). The success rate of DP+TMP was in the same range as it is known for the standard regimens, whereas the rate of severe side effects appears to be lower. The results suggest that in AIDS patients DP+TMP may be used as first line treatment of PCP which is not severe enough for hospitalisation.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Dapsone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP.. We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months.. In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017).. In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Recurrence; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To compare cotrimoxazole and eflornithine as primary treatment for first-episode Pneumocystis carinii pneumonia (PCP).. Prospective open-labelled study.. Patients were randomized to eflornithine (400 mg/kg daily, as a continuous intravenous infusion) or cotrimoxazole (3.84 g twice daily, intravenously) for 14 days.. Only 39% of patients treated with eflornithine (20 out of 51) and 40% of those given cotrimoxazole (nine out of 47) successfully completed therapy. Although 12 out of the 36 patients with confirmed PCP were treated successfully with eflornithine, significantly more patients were withdrawn from the eflornithine group because of therapy failure (25 out of 51 versus 10 out of 47, P = 0.007). This significant difference persisted in patients in whom a diagnosis of PCP was confirmed histologically (19 out of 33 versus seven out of 27, P = 0.03). Significantly more patients were withdrawn from cotrimoxazole because of serious drug-related side-effects (38 versus 12%, P = 0.005).. Eflornithine (400 mg/kg daily) is less effective than cotrimoxazole (7.68 g daily) as treatment for first-episode PCP. Eflornithine does have activity against P. carinii in humans.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Chemotherapy, Adjuvant; Eflornithine; Female; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; 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

Microsporidial myositis caused by Trachipleistophora hominis is a life-threatening and emerging microsporidiosis among immunocompromised hosts. This article reports a case of disseminated microsporidiosis caused by T. hominis in southern Thailand. The patient had HIV and presented at the clinic with incapacitating muscle pain. She was diagnosed with disseminated microsporidiosis. Molecular identification revealed the sequence of 18S ribosomal RNA gene involving sequences sharing 99% nucleotide identity with T. hominis from an Australian patient. To our knowledge, this is the first study to report the detection of T. hominis microsporidia in an HIV patient in Thailand.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Albendazole; Clindamycin; Female; Humans; Immunocompromised Host; Microsporidia; Microsporidiosis; Thailand; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Crystallization; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Urinalysis; Urine

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmic encephalitis (TE) in immunocompromised patients. We describe a case of a 29-year-old Japanese man presenting with headache and vomiting. He had previously been diagnosed with human immunodeficiency virus infection. Magnetic resonance imaging identified some nodules in his brain. We suspected TE and began treatment successively with parenteral trimethoprim-sulfamethoxazole (TMP/SMX) plus clindamycin. After that, we switched to pyrimethamine plus sulfadiazine (PMT/SDZ) because these drugs are the first-line treatment for TE. Because the patient experienced nausea and vomiting, PMT/SDZ was replaced with TMP/SMX, atovaquone, and clindamycin. However, the patient could not tolerate them owing to their adverse reactions. Thus, we attempted oral desensitization to TMP/SMX to treat his TE. We began desensitization with 0.4/2 mg of TMP/SMX. The patient experienced morbilliform rash and elevated aminotransferase levels. Therefore, we administered a glycyrrhizin and an antihistamine and continued the last tolerable dose until these symptoms improved. After 37 days, we achieved desensitization to 160/800 mg of TMP/SMX, and the patient's symptoms improved. After using nested-polymerase chain reaction to identify T. gondii DNA in his frozen cerebrospinal fluid, which was collected at admission, his diagnosis was confirmed as TE. This might be the first case to attempt desensitization to TMP/SMX to treat TE.

Topics: Adult; AIDS-Related Opportunistic Infections; Atovaquone; Brain; Clindamycin; Coccidiostats; Desensitization, Immunologic; Humans; Male; Toxoplasmosis, Cerebral; 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

Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE.. A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service.. The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; Brain; Female; HIV; Humans; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Toxoplasma; Toxoplasmosis, Cerebral; 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

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

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

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Female; HIV; Humans; Pregnancy; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antiprotozoal Agents; Child; Child, Preschool; Critical Pathways; Databases, Factual; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Young Adult

The most common clinical presentation of Toxoplasma gondii in HIV patients is encephalitis; however, the intramedullary involvement has been reported in a few cases. We report a case of intramedullary toxoplasmosis in a female patient diagnosed with HIV/tuberculosis co-infection, and history of poor adherence to antiretroviral therapy. The patient developed subacute paraparesis with compromise of sensory function and urinary sphincter. The nuclear magnetic resonance evaluation showed a single intramedullary ring-enhanced lesion at the T-8 level which was solved after an anti-Toxoplasma therapy with trimethoprim/sulfamethoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Central Nervous System Protozoal Infections; Coinfection; Dexamethasone; Female; Humans; Magnetic Resonance Imaging; Spinal Cord Diseases; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Caspofungin; Chile; Dapsone; Dihydropteroate Synthase; Echinocandins; Female; Humans; Lipopeptides; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; 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

We report a patient with AIDS who had an anaphylactic-like reaction from trimethoprim-sulfamethoxazole. Clinical suspicion of anaphylaxis should be considered in patients presenting with fever, hypotension, eosinophilia, rash, flushing or pulmonary infiltrates after initial exposure and re-exposure to the medication. This case highlights the need for healthcare professionals to be reminded of the association between this unusual antibiotic reaction resembling sepsis and HIV disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Fever; Humans; Pneumonia, Pneumocystis; Transgender Persons; Trimethoprim, Sulfamethoxazole Drug Combination

To identify the incidence of and predictors for tuberculosis in children living with HIV in Northern Ethiopia.. Observational, retrospective follow-up study.. A total of 645 HIV-infected children were observed between September 2009 and September 2014. Cox regression analysis was used to identify predictors for developing TB.. The incidence rate of tuberculosis was 4.2 per 100 child-years. Incidence of tuberculosis was higher for subjects who were not on cotrimoxazole preventive therapy, were not on isoniazid preventive therapy, had delayed motor development, had a CD4 cell count below the threshold, had hemoglobin level less than 10 mg/dl and were assessed as World Health Organization (WHO) clinical stage III or IV.. Incidence of TB in children living with HIV was high. This study reaffirmed that isoniazid preventive therapy is one of the best strategy to reduce incidence of TB in children living with HIV. All children living with HIV should be screened for TB but for children with delayed motor development, advanced WHO clinical stage, anemia or immune suppression, intensified screening is highly recommended.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Antitubercular Agents; Child; Child, Preschool; Ethiopia; Female; Follow-Up Studies; Humans; Incidence; Isoniazid; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

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

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

The current standard treatment for cerebral toxoplasmosis (pyrimethamine/sulfadiazine) often encounters problems of poor tolerability, adverse effects, frequent dropouts and non-availability of pyrimethamine/sulfadiazine in some parts of India. We have had to use the combination of two effective alternative agents for toxoplasmosis, cotrimoxazole and clindamycin, on compassionate grounds. This retrospective observational study reports superior efficacy and better tolerability of cotrimoxazole/clindamycin compared to the recommended regimen. Primary end-point (complete response) was defined as more than 50% improvement of clinical status or more than 50% decrease in the size of brain lesions after two weeks of treatment initiation. Complete response occurred more commonly with cotrimoxazole/clindamycin than with pyrimethamine/sulfadiazine group (80% vs. 31.25%, respectively, relative risk 2.56, 95% confidence interval: 1.21-5.43). There was a trend towards higher on-treatment mortality in the pyrimethamine/sulfadiazine group in comparison to the cotrimoxazole/clindamycin (mortality rate 37.5% in pyrimethamine/sulfadiazine vs 12% in cotrimoxazole/clindamycin, p = 0.07, relative risk = 3.125, 95% confidence interval: 0.91-10.75). Overall, 62.5% (10/16) of patients on pyrimethamine/sulfadiazine suffered drug-related adverse reactions compared to 24% (6/25) on cotrimoxazole/clindamycin (p = 0.02, relative risk = 2.60, 95% confidence interval: 1.17-5.76). The commonest complication of pyrimethamine/sulfadiazine was severe thrombocytopenia with major bleeding (4/16, 25%). We propose that the new combination chemotherapy, which is widely available, effective and safe, can be used in developing countries.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Female; Humans; India; Male; Middle Aged; Poverty; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

Topics: Acidosis, Lactic; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anemia, Hemolytic; Antifungal Agents; Cryptococcus neoformans; Drug Therapy, Combination; Female; Humans; Male; Meningitis, Cryptococcal; Renal Insufficiency; Thrombocytopenia; Treatment Outcome; 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 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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antimalarials; Chemoprevention; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; HIV-1; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

As the incidence of HIV infection has increased its neurological complications are being encountered in our clinical practice. Toxoplasmosis is a common cerebral opportunistic infection seen in HIV-infected patients, even though the incidence has declined with the use of antiretroviral therapy. Establishing a definitive diagnosis of cerebral toxoplasmosis is difficult in resource limited settings.. A 20 year old gentleman was referred to our institute as a case of stroke. Magnetic resonance imaging (MRI) of his brain showed multiple ill-defined and nodular enhancing lesions in bilateral supratentorial and infratentorial neuroparenchyma. Test for HIV-1 was reactive. Toxoplasma serology revealed raised IgG antibody levels. Based on the MRI features and positive toxoplasma serology a diagnosis of cerebral toxoplasmosis was made. He was treated with trimethoprim/sulfamethoxazole and pyrimethamine/ Sulfadoxine for 3 weeks. After 2 weeks of treatment, repeat MRI of brain was done which showed significant resolution of the lesions.. We are presenting this case to highlight the fact that cerebral toxoplasmosis should be considered in the differential diagnosis of multiple neuroparenchymal lesions in young individuals who present with neurological deficits.

Topics: AIDS-Related Opportunistic Infections; Antibodies, Protozoan; Brain; Drug Combinations; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Pyrimethamine; Serologic Tests; Stroke; Sulfadoxine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.. A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.. 202 children [median (interquartile range, IQR) age 3.2 (2.1- 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 - 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.. The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.

Topics: AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Cytomegalovirus Infections; Female; Fluorescent Antibody Technique; HIV Seronegativity; Humans; Incidence; Infant; Male; Nasopharynx; Oxygen; Pneumocystis; Pneumonia, Pneumocystis; Pneumonia, Viral; Predictive Value of Tests; Prednisone; Prospective Studies; Real-Time Polymerase Chain Reaction; Risk Factors; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

The Pneumocystis and Pneumocystosis: first meeting of experts from Latin-American and Portuguese-speaking countries was held in Lisbon, Portugal, on 24-26 October 2013. A total of 20 speakers from Latin America, Africa and Europe participated in the meeting. The epidemiological studies presented in this meeting begin to change the misconception that since the AIDS epidemic, Pneumocystis pneumonia (PcP) has become an infrequent disease, showing that today PcP remains a major opportunistic infection in HIV-infected patients in both developed and developing countries and an emerging problem in immunocompromised patients without HIV infection worldwide. PcP management remains a challenge. Right now, the combination of caspofungin and trimethoprim-sulfamethoxazole (TMP-SMX) is a promising therapeutic approach that needs to be assessed in controlled clinical trials.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Caspofungin; Developed Countries; Developing Countries; Echinocandins; Humans; Immunocompromised Host; Latin America; Lipopeptides; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Humans; 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

Contributors to fatal outcomes in TB/HIV co-infected patients actively undergoing TB treatment are poorly characterized. The aim was to assess factors associated with death in TB/HIV co-infected patients during the initial 6 months of TB treatment.. We conducted a hospital-based retrospective cohort study from January 2006 to December 2013 at the Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify hospitalized co-infected TB/HIV patients aged 15 years and older. Death was defined as any death occurring during TB treatment, as per the World Health Organization's recommendations. We conducted logistic regression analysis to identify factors associated with a fatal outcome. Magnitudes of associations were expressed by adjusted odds ratio (aOR) with 95% confidence interval.. The 337 patients enrolled had a mean age of 39.3 (standard deviation 10.3) years and 54.3% were female. TB treatment outcomes were distributed as follows: 205 (60.8%) treatment success, 99 (29.4%) deaths, 18 (5.3%) not evaluated, 14 (4.2%) lost to follow-up, and 1 (0.3%) failed. After exclusion of patients lost to follow-up and not evaluated, death in TB/HIV co-infected patients during TB treatment was associated with a TB diagnosis made before 2010 (aOR = 2.50 [1.31-4.78]; p = 0.006), the presence of other AIDS-defining diseases (aOR = 2.73 [1.27-5.86]; p = 0.010), non-AIDS comorbidities (aOR = 3.35 [1.37-8.21]; p = 0.008), not receiving cotrimoxazole prophylaxis (aOR = 3.61 [1.71-7.63]; p = 0.001), not receiving antiretroviral therapy (aOR = 2.45 [1.18-5.08]; p = 0.016), and CD4 cells count <50 cells/mm3 (aOR = 16.43 [1.05-258.04]; p = 0.047).. The TB treatment success rate among TB/HIV co-infected patients in our setting is low. Mortality was high among TB/HIV co-infected patients during TB treatment and is strongly associated with clinical and biological factors, highlighting the urgent need for specific interventions focused on enhancing patient outcomes.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antitubercular Agents; Cameroon; Cause of Death; Cohort Studies; Coinfection; Comorbidity; Female; Hospitals; Humans; Male; Middle Aged; Retrospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

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

Pneumocystis jirovecii pneumonia (PcP) is a well-recognized major opportunistic infection in HIV-infected patients. During the 1980s, the HIV pandemic turned PcP into a major worldwide medical and public health problem. With the introduction of Pneumocystis chemoprophylaxis and the development of highly active antiretroviral therapy (ART) for the treatment of HIV infection, there has been a decrease in PcP incidence in developed countries. However, the prevalence of AIDS-related PcP in developing countries remains high because a lot of people do not have access to ART or ignore their HIV infection status. This article discusses the information available about PcP among Latin American countries where there is a great regional heterogeneity in the prevalence of HIV infection and in ART coverage, as well as in the observed frequencies of PcP that range from 5.9 to 55% in this area.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Coinfection; Developing Countries; Female; HIV; Humans; Latin America; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prevalence; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Combined Modality Therapy; Dacryocystitis; Dacryocystorhinostomy; Eye Infections, Fungal; Fatal Outcome; Female; Fluorescent Antibody Technique, Direct; HIV-1; Humans; Lacrimal Apparatus; Paracoccidioides; Paracoccidioidomycosis; Radiography; RNA; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult

The case is presented of a 38 year-old patient who was admitted in the Emergency Department due to a severe acute respiratory failure and who was transferred to the Critical Care Unit with a suspected initial diagnosis of community acquired pneumonia caused by an atypical microorganism, which was complicated with an acute respiratory distress syndrome. This was able to be treated with non-invasive mechanical ventilation. At 48 hours after admission, the growth of Gram negative bacilli in the blood culture was reported, which was subsequently identified as Salmonella enteritidis. This information, along with the lymphopenia suffered by the patient, suggested an immunodepressed state, thus serological tests were performed which showed positive for HIV. Antibiotic treatment was started based on the microbiological findings, with a favourable clinical outcome for the patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Bacteremia; Bronchoalveolar Lavage Fluid; Ceftriaxone; Cocaine-Related Disorders; Community-Acquired Infections; Diagnosis, Differential; Female; Humans; Lymphopenia; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Respiratory Distress Syndrome; Salmonella enteritidis; Salmonella Infections; 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

Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.. TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models.. There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p<0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years.. Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Asia; CD4 Lymphocyte Count; Dapsone; Databases, Factual; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole is a commonly used drug in the treatment and prophylaxis of opportunistic infections in HIV seropositive patients. We report a case of a 35-year-old HIV-infected man who presented with blurring of vision one week following initiation of co-trimoxazole therapy. A diagnosis of co-trimoxazole-induced myopia, a known idiosyncratic drug reaction, was made. The drug was withheld and the myopia resolved completely. Although in this patient the ocular condition resolved completely, serious ocular adverse reactions have also been reported with co-trimoxazole. This case report highlights the occurrence of ocular adverse drug reactions (ADRs) in HIV-infected patients on co-trimoxazole and the complexity of drug interactions.

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

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

Topics: Acute Kidney Injury; Adult; AIDS-Associated Nephropathy; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Diagnosis, Differential; HIV Seropositivity; Humans; Male; Medication Adherence; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Renal Dialysis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Within the health policy field, a growing literature is attempting to understand the diverse responses of policy makers to research, and to explain why certain research findings make their way into policy while others are effectively ignored. In this paper we apply a policy analysis framework to the development of cotrimoxazole prophylaxis national policy in Malawi. Arguing that Malawi was one of the early adopters of cotrimoxazole prophylaxis at a national level, we show how the research to policy process was influenced by national healthcare context, the networks of individuals involved, and the nature of the public health evidence itself.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Biomedical Research; Evidence-Based Medicine; Health Policy; Humans; Malawi; Policy Making; Trimethoprim, Sulfamethoxazole Drug Combination

A 47-year-old man with optimally controlled type-2 diabetes mellitus and chronic hepatitis B was admitted to a local hospital because of a 1-week history of cough and high-grade fever. He was diagnosed with Pneumocystis pneumonia (PCP) and Klebsiella pneumonia from a chest radiograph and sputum. Simultaneously, he was found to have HIV infection with a CD4 count of 76/μl. Despite alteration of treatment secondary to the development of allergic reaction to trimethoprim-sulfamethoxazole (TMP-SMX), the patient was able to complete a 3-week therapy for PCP after being switched to pentamidine isetionate. After the treatment of PCP, he was referred to our hospital for the initiation of anti-HIV therapy. He presented with recurrent high-grade fever of a few days' duration prior to his initial visit, which subsequently led to his admission. Chest computed tomography (CT) showed the enlargement of a previously identified infiltrate in the left upper lung field, and the sputum culture upon admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia exalbida. Due to his allergy to sulfonamide, the patient was treated with imipenem (IMP) and amikacin (AMK) given intravenously for 17 days, followed by garenoxacin (GRNX) taken orally for 6 months, without any adverse effects. The chest infiltrate resolved completely, and he remains stable without relapse 8 months after the completion of the therapy. Pulmonary nocardiosis should be considered as a differential diagnosis of recurring pneumonia in immunocompromised patients, especially in HIV-infected individuals. Oral administration of GRNX following IMP and AMK can be used as an alternative to TMP-SMX therapy in cases of pulmonary nocardiosis caused by N. exalbida.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Fluoroquinolones; Humans; Male; Middle Aged; Nocardia; Nocardia Infections; Pentamidine; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Sputum; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective study was performed on case reports of Pneumocystis pneumonia (PCP) from 1959 to 2009 in mainland China. The epidemiological characteristics of PCP over half a century were investigated over two time spans. The first was from 1959, when the first incidence of PCP was reported, to 1984, before the emergence of AIDS in mainland China. The second was from 1985, when the first AIDS case was reported in mainland China, to the end of 2009. A total of 2351 PCP cases were reported during these two time spans, covering a 51-year period. Only seven PCP cases were reported during the first time span. Six were diagnosed by autopsy, accordingly without treatment, whilst the other was diagnosed by open lung biopsy in a living patient who eventually recovered following treatment with sulfadiazine and pyrimethamine. The other 2344 PCP cases were reported during the second time span (1985-2009) from 21 provinces, four municipalities and three autonomous regions. Among the 2344 PCP cases, 70.22 % (1646/2344) were identified together with human immunodeficiency virus (HIV) infection or were in AIDS patients. The remaining 698 non-HIV-infected patients had undergone organ transplantation, had other underlying diseases such as malignancy or hypoimmunity, or had undetermined diagnosis. The results of statistical analysis indicated that AIDS was the most common underlying disease of PCP for patients <1 year and >14 years. For patients aged between 1 and 14 years, haematological malignancy was the most common underlying disease. The trend of the underlying diseases changed with time, showing that the number of PCP patients afflicted by HIV/AIDS increased dramatically, reaching almost threefold during the most recent 5 years compared with the level of the previous 10 years. The number of patients undergoing organ transplantation or with other underlying diseases rose constantly, but the number of malignancies tended to decline from 1995-2004 to 2005-2009. During the second time span (1995-2009), most of the patients (97.61 %) were diagnosed alive and only 56 cases (2.39 %) were identified by autopsy. The mortality of PCP patients treated with anti-Pneumocystis drugs was 14.61 % for those with HIV/AIDS and 15.84 % for those without HIV/AIDS. For the PCP patients without anti-Pneumocystis treatment, all (100 %) of the HIV/AIDS-associated PCP patients died, whilst 13.79 % (4/29) of non-HIV-infected PCP patients survived. These data from epidemiological investigation

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Child; Child, Preschool; China; Female; History, 20th Century; History, 21st Century; Humans; Immune System Diseases; Infant; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Transplants; 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

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

Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.. We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options.. For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Clinical Laboratory Techniques; Cost of Illness; Cost-Benefit Analysis; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Reproducibility of Results; Sensitivity and Specificity; South Africa; Sputum; Staining and Labeling; Trimethoprim, Sulfamethoxazole Drug Combination

Primary cutaneous actinomycosis is very uncommon. We report a patient with cutaneous actinomycosis with multiple lesions without any detectable extra-cutaneous lesions. In our patient the actinomycosis was the presenting manifestation of HIV infection.

Topics: Actinomyces; Actinomycosis; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Combined Modality Therapy; Debridement; HIV Seropositivity; Humans; Male; Skin Diseases, Bacterial; Skin Ulcer; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

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

The clinical features of pneumocystis pneumonia (PCP) differ according to the predisposing factors responsible for immunosuppression. Although PCP in patients with acquired immunodeficiency syndrome (AIDS) has been extensively described, its characteristics in non-AIDS patients, such as those with malignancies, are not thoroughly documented.. To characterize and compare the clinical and imaging features of PCP in patients with malignancies with those in AIDS patients.. A multi-center retrospective study.. We evaluated the clinical and radiological features of PCP in 21 patients with malignancies and in 17 with AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome were examined.. The patients with malignancies showed shorter durations of symptoms before PCP was diagnosed. The levels of serum markers and the oxygenation index did not differ. CT showed diffuse or widespread ground-glass opacity (GGO) in all of the patients evaluated. None of the AIDS patients demonstrated consolidation, whereas half of the patients with malignancy showed consolidation along with GGO. The extent of GGO scored on CT images was significantly greater in the AIDS patients. No correlation was observed between the CT findings and other clinical parameters. All of the AIDS patients recovered from PCP, whereas six patients with malignancies died within a month after the onset of PCP.. The characteristics of the CT images differed between the patient groups with different underlying disorders, although it remains to be determined whether CT findings are associated with other clinical features or are predictive of the outcome of PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Biomarkers; Female; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Oxygen; Pneumonia, Pneumocystis; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In order to evaluate the incidence rate and possible risk factors associated with AIDS-related malignancies and infections (ARMI) we performed data analysis of clinical charts of HIV patients in two hospital cohorts, that started high activity antiretroviral therapy (HAART) between July 2003 and October 2007. Trimethoprim-sulfamethoxazole and Azithromycin prophylaxis was provided according to current guidelines. We evaluated development of ARMI six months after-starting HAART and its association with clinical and epidemiological variables. Of 235 patients analyzed -118 women (50.2%) and 117 men (49.8%)- 11 presented ARMI: 3 pulmonary TB and 3 lymph nodes TB cases, 3 cases with meningeal Cryptococcus, one Chagas's disease presenting brain mass and one with non-Hodgkin lymphoma. ARMI incidence: 4.7%. A CD4 cell count < 100/150 was associated with risk of developing ARMI. The mean CD4 cell count was 73 in patients who developed ARMI and 143 in those who did not. No association was found with the other analyzed variables. In the CD4 cell count < 150 group one out of 4 patients with reactive serology presented Chagas's disease causing brain mass; none of the 46 patients with reactive serology presented toxoplasmosis encephalitis. The incidence rate of ARMI was 4.7%. TB in first place and cryptococcosis in second were the AIDS events more frequently observed. A low CD4 cell count was the only observed risk factor statistically associated with development of ARMI. The role of prophylaxis in this population should be re-evaluated.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Argentina; Azithromycin; CD4 Lymphocyte Count; Female; Humans; Male; Neoplasms; Odds Ratio; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

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

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

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

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

To report hypoglycaemia, a life-threatening adverse event, associated with trimethoprim-sulfamethoxazole. A sulfonylurea-like effect, leading to insulin raise, was investigated.. Two cases of trimethoprim-sulfamethoxazole-associated hypoglycaemia in 2 patients with a diagnosis of new HIV-1-infection presenting with Pneumocystis jiroveci pneumonia are reported. The patients had no predisposing factors, such as renal or liver impairment, interfering with trimethoprim-sulfamethoxazole elimination, thus leading to hypoglycaemia. Insulin plasma levels were measured in both patients.. Severe hypoglycaemia was associated with increased serum levels of insulin up to 84 microU/ml (normal values < 10 microU/ml). Continuous dextrose infusion was necessary, further suggesting the sulfonylurea-like effect of sulfamethoxazole. Interestingly, plasma levels of insulin progressively raised after trimethoprim-sulfamethoxazole administration.. Only 18 cases of trimethoprim-sulfamethoxazole associated hypoglycaemia are reported in the literature. Hypoglycaemia is a life-threatening condition, likely underreported, to consider when trimethoprim-sulfamethoxazole administration is required, even in the absence of predisposing factors or other hypoglycaemic agents. Physician should bear in mind the potential trimethoprim-sulfamethoxazole-associated adverse event especially when prolonged treatments and elevated dosage are used.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Blood Glucose; Female; Glucose; Humans; Hypoglycemia; Insulin; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Nocardia infections are rare among normal individuals. Mostly they occur in immuno-compromised individuals. Here, we report a case of pulmonary nocardiosis in a person who was diagnosed as having pulmonary tuberculosis and was treated with anti-tuberculous treatment for 6 months. But the sputum smear was positive even after a complete course of treatment. The patient was seropositive to HIV-1 antibodies.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antitubercular Agents; Coinfection; HIV-1; Humans; Male; Nocardia asteroides; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are associated with failure of sulfur prophylaxis of Pneumocystis pneumonia. Here the P. jirovecii DHPS gene was amplified from bronchoalveolar fluid of 10 AIDS patients in China. No DHPS gene mutations were observed. The results suggest that the prevalence of DHPS mutations in China may be low.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Bronchoalveolar Lavage Fluid; China; Dihydropteroate Synthase; Female; Genes, Fungal; Humans; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cholestasis, Intrahepatic; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Sulfamethoxazole in combination with trimethoprim (cotrimoxazole) is used for prophylaxis and treatment of several opportunistic infections in HIV-infected patients. It is associated with a high incidence of hypersensitivity reactions, which is thought to have an immune basis. Genetic polymorphisms in MHC are known to predispose to hypersensitivity reactions to a structurally diverse group of drugs in HIV-positive patients. The aim of the study was to determine whether functional polymorphisms in TNF, LTA, HSPA1L and HLA-DRB1 genes influence the risk of cotrimoxazole hypersensitivity in HIV-infected patients.. We genotyped 136 HIV-positive patients with (n = 53) and without (n = 83) cotrimoxazole hypersensitivity using a combination of PCR-based techniques, including PCR-restriction fragment length polymorphisms, PCR-sequence specific oligonucleotides and real-time PCR. Genotypes and the haplotype frequencies were analyzed using the chi(2) test in the Haploview and CLUMP programs.. No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls.. Our data show that MHC polymorphisms are not major predisposing factors for cotrimoxazole hypersensitivity, although we cannot exclude a minor contribution. An environmental factor (i.e., HIV infection) seems to predominate over any of the genetic factors so far investigated in increasing the risk of cotrimoxazole hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Female; Haplotypes; HLA-DR Antigens; HLA-DRB1 Chains; HSP70 Heat-Shock Proteins; Humans; Lymphotoxin-alpha; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

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

Topics: Acute Kidney Injury; Adenine; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Fatal Outcome; Humans; Kidney Diseases; Male; Middle Aged; Multiple Organ Failure; Organophosphonates; Pneumocystis carinii; Pneumonia, Pneumocystis; Recurrence; Renal Dialysis; Tenofovir; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Renal

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

A retrospective case-notes audit of 359 HIV-1-infected adult patients with first-episode laboratory-confirmed Pneumocystis jirovecii pneumonia treated with co-trimoxazole (from 1987 adjuvant steroids were used if PaO(2) <9.3 kPa) showed that only 230/359 (64%) patients completed treatment; 104 (29%) patients had treatment-limiting toxicity; rash occurred in 4/60 (6.7%) patients in 1985-1988 and in 15/47 (31.9%) in 2005-2008. Twenty-five patients (7%) failed co-trimoxazole treatment. Overall mortality was 13.6% (49/359); mortality among patients who failed co-trimoxazole treatment was 48% (12/25) and by contrast mortality was 4.8% (5/104) among patients with treatment-limiting toxicity.

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

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Bone Marrow Diseases; Diarrhea; Duodenal Diseases; Edema; Enteral Nutrition; Humans; Hypotension; Leg; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of trimethoprim/sulphamethoxazole treatment on the natural population of lactic acid bacteria in the intestinal tract and to determine if any of the strains developed resistance to antibiotics.. Lactic acid bacteria were isolated from stool samples of 100 children. The isolates were identified based on biochemical characteristics and DNA profiles obtained from polymerase chain reaction with genus- and species-specific primers. Resistance to sulphamethoxazole, streptomycin, compound sulphonamides, chloramphenicol and vancomycin was tested using the paper-disk method.. The lactic acid bacteria were identified as Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus paracasei, Lactobacillus pentosus, Lactobacillus rhamnosus, Leuconostoc mesenteroides subsp. mesenteroides, Enterococcus spp. and Weissella spp. Lactobacillus plantarum and Bifidobacterium spp. were not isolated. All strains, except two, were sensitive to chloramphenicol and streptomycin. Thirty-five percent of the isolates were resistant to vancomycin, 50% to compound sulphonamides and 66% to sulphamethoxazole.. Treatment with trimethoprim/sulphamethoxazole repressed a large number of lactic acid bacteria normally present in the intestinal tract of children. A number of strains were resistant to sulphamethoxazole and may be used as probiotics to correct the imbalance in lactic acid bacteria.

Topics: AIDS-Related Opportunistic Infections; Colony Count, Microbial; Feces; Gastrointestinal Tract; HIV Seropositivity; Humans; Infant; Lactobacillus; Microbial Sensitivity Tests; Probiotics; South Africa; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

A 26-year-old Thai man presented with progressive dyspnea for four months and right pleuritic chest pain two days before admission. The chest radiograph showed massive right pleural effusion. Thoracentesis was done, and the culture grew Nocardia spp as well as positive strain for acid-fast bacilli. An anti-HIV test was reactive, with a CD4 count of 12 cells/mm3. The patient was treated with inter-costal tube drainage (ICD) inserted for empyema thoracis. The antimicrobials used trimethoprim-sulfamethoxazole and anti-TB drugs CAT-1 orally. One month later, anti-retroviral therapy with HAART was initiated. At follow-up after 6 months, he was healthy appearing, with a nearly normal chest radiograph.

Topics: Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Empyema, Tuberculous; Humans; Male; Nocardia Infections; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line therapy for patients failing or developing toxicity to first-line therapy.. A case note review of 1122 patients with 1188 episodes of HIV-associated PCP from three observational cohorts in Copenhagen, London and Milan, between 1989 and 2004, was conducted.. Trimethoprim/sulfamethoxazole (962 PCP episodes, 81%) was the most frequently used first-line therapy, followed by intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes, 6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled pentamidine; 67 episodes, 6%). Rates of unchanged therapy were trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%) episodes and because of toxicity in 198 (17%) episodes. Three month survival rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and pentamidine = 76% (P = 0.09). After adjustment for possible confounders, pentamidine was associated with a significantly greater risk of death at 3 months [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%; clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable time-updated Cox regression analysis showed a greater risk of death associated with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for clindamycin/primaquine, when both were compared with trimethoprim/sulfamethoxazole.. Pentamidine was associated with a greater risk of death when used as first- and second-line therapy for HIV-associated PCP, and was associated with more treatment changes. Clindamycin/primaquine appeared superior to pentamidine as second-line therapy for PCP in patients failing or developing toxicity with trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non-trimethoprim/sulfamethoxazole regimens, second-line therapy should be trimethoprim/sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Clindamycin; Cohort Studies; Denmark; Female; Humans; Italy; London; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; 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

Symptomatic primary HIV infection occurs in an estimated 50% to 90% of patients. A constellation of symptoms that most closely resembles those of acute infectious mononucleosis characterizes the syndrome. On rare occasions, opportunistic infections present simultaneously with primary HIV infection. We describe a patient who presented with an episode of severe Pneumocystis jiroveci pneumonia during what appeared to be a prolonged primary HIV infection. Serological testing demonstrated the progressive development of reactive bands on serial Western blot determinations. This case highlights how primary HIV infection can produce profound immunosuppression through CD4 lymphocytopenia predisposing patients to opportunistic infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Opportunistic infections are the leading cause of mortality among HIV-infected people. Several simple interventions prevent illness, prolong life, or prevent HIV transmission from HIV-infected people in Africa. These include: cotrimoxazole prophylaxis; insecticide-treated bed nets; supplies for household water treatment and safe storage; materials promoting family voluntary counselling and testing (VCT); and condoms. We provided these interventions to adults and children with HIV who were members of the AIDS Support Organization in Uganda. To evaluate use of this basic care and prevention package, we surveyed a representative sample of 112 clients of TASO in their homes. Among respondents, 95% reported taking cotrimoxazole everyday, 89% said they had slept under a bednet the night before, 65% reported current treatment of household drinking water, 89% of sexually active respondents reported using condoms, and 96% reported family use of VCT. Household observations verified that use of cotrimoxazole, bednets, and water treatment products were consistent with reported use. This evaluation suggests successful distribution and use of basic care and prevention services at an AIDS organization in Uganda.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bedding and Linens; Condoms; Counseling; Delivery of Health Care; Female; Humans; Insecticides; Malaria; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Water Purification

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Inflammatory Agents; Antiretroviral Therapy, Highly Active; Hodgkin Disease; Humans; Immune Reconstitution Inflammatory Syndrome; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Pulmonary cryptococcosis is an unusual fungal infection that is most often found in AIDS or in organ transplant recipients. Although in immunocompromised patients, cryptococcal infection often causes pulmonary infections, the diagnosis of lung involvement is generally difficult. The presentation of pulmonary cryptoccosis in HIV-infected patients appears to be more acute and severe than in other immunocompromised patients, probably related with the severe immunosuppression. Diffuse infiltrates, mediastinal and hilar lymph nodes enlargement are the most common radiological findings in AIDS-associated pulmonary cryptococcosis. Cavitation is a rare form of and includes only 10% to 15% of all cases. Only a few case reports or studies with small number of patients of pulmonary cryptococcosis have been published over the past two decades. We report a case of an AIDS patient who developed cavitary pneumonia as the only clinical expression of cryptococcosis.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcosis; Diagnosis, Differential; Fluconazole; Humans; Itraconazole; Lung Diseases, Fungal; Male; Tomography, X-Ray Computed; 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

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Eye Infections, Fungal; Fluorescein Angiography; Humans; Male; Pneumonia, Pneumocystis; Retinal Vein Occlusion; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Humans; Malaria; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

AIDS-associated otic pneumocystosis is rare. Of 14 cases documented mainly as case reports up to now, only 1 has been reported in the surgical pathology literature. We report 6 males, mean age of 32.3 years, with external auditory canal masses and otorrhea. Two biopsies contained a predominance of granulation tissue with a mixed inflammatory cell infiltrate and elusive foci of foamy exudate. In contrast, 4 biopsies demonstrated conspicuous angiocentric mantles of stippled, foamy exudate. Fibrin was noted in intravascular, perivascular, and intervascular locations. One biopsy demonstrated bordering of the foamy exudate by a palisaded granulomatous reaction, with adjacent discrete giant cell-containing granulomas. Special stains confirmed trophozoites and cysts within the foamy exudate. Review of 2 initial "nondiagnostic" biopsies confirmed granulation tissue and necrotic debris in which Pneumocystis jiroveci was identified in focal foamy exudate. After the diagnosis of otic pneumocystosis, all patients were initiated on trimethoprim-sulfamethoxazole. One patient also had dapsone. Two patients succumbed to pulmonary tuberculosis and 2 were lost to follow-up. One patient with pneumocystis pneumonia did not return for follow-up after 6 weeks. One patient experienced complete resolution of the mass on medical therapy, and is disease free for 4 years. Heightened recognition of the characteristic foamy exudate in an unconventional location remains the gold standard in the timely diagnosis of this eminently treatable disease. In all patients, otic pneumocystosis served as the sentinel of underlying HIV infection and AIDS.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Male; Otitis Media; Pneumocystis Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Daily prophylaxis with trimethoprim-sulfamethoxazole (cotrimoxazole) by persons with HIV reduces morbidity and mortality and is recommended by Joint United Nations Program on HIV/AIDS and World Health Organization (WHO), but there are limited published cost-effectiveness data for this intervention. We assessed the cost-effectiveness of cotrimoxazole prophylaxis for persons living with HIV in rural Uganda.. We modeled the cost-effectiveness of daily cotrimoxazole prophylaxis based on clinical results and operational data from a prospective cohort study of home-based care delivery to adults and children with HIV in rural Uganda who were older than the age of 5 years. Main outcome measures were net program cost and disability-adjusted life-years (DALYs) gained. We examined the provision of cotrimoxazole prophylaxis for (A) all HIV-infected individuals regardless of immunologic or clinical criteria; (B) those with WHO stage 2 or more advanced disease; (C) those with CD4 cell counts <500 cells/microL; and (D) those meeting criteria B or C, the current WHO recommendation. We calculated the costs and effectiveness of these 4 screening algorithms compared with no cotrimoxazole prophylaxis and calculated incremental cost-effectiveness ratios. We performed univariate and multivariate sensitivity analyses.. Cotrimoxazole prophylaxis for all HIV-infected individuals (algorithm A) produced 7.3 life-years and 7.55 DALYs per 100 persons over 1 year compared with no prophylaxis. Using this screening algorithm, the intervention saved $2.50 per person-year. The program costs and the DALYs gained by algorithms A, B, and D were more favorable than those for algorithm C. Among algorithms A, B, and D, strategies using screening algorithms for WHO stage or CD4 cell counts were more costly and marginally less effective than providing cotrimoxazole prophylaxis to all HIV-infected individuals.. Daily cotrimoxazole prophylaxis for HIV-infected individuals is highly cost-effective in rural Uganda. The use of screening algorithms to identify individuals with advanced HIV disease may result in higher program costs and less favorable cost-effectiveness.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Chemoprevention; Child; Cost-Benefit Analysis; Humans; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

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

We examined the outcomes of a World Health Organization (WHO) recommended programme offering cotrimoxazole (CTM) prophylaxis to 908 HIV-positive individuals in rural Zimbabwe, who accepted enrolment in the treatment programme. Outcomes included duration in programme, time between visits, relationship and marital status. Mean duration of participation in the programme was 224 days. The mean time between visits decreased from 11.2 weeks, between visit 1 and 2, to 4.3 weeks between visit 11 and 12. Statistical analysis showed significant positive correlations between duration in programme and participant age, participant relationship status and the partner's state of affairs. Statistical analysis showed no significant correlation between duration in programme and gender. Results indicate that if continuation is demonstrated for the first 4 to 6 months, participants will continue with the CTM programme. Results also reflect the constrained feasibility of CTM prophylaxis in rural Africa as well as the need to target subpopulations, such as young people, patients and their spouses for focused HIV/AIDS education initiatives.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Child, Preschool; Feasibility Studies; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Rural Health; Social Environment; Trimethoprim, Sulfamethoxazole Drug Combination; Zimbabwe

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

Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP).. Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review.. High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028).. The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Dihydropteroate Synthase; Disease Progression; DNA, Intergenic; Female; Genes, Viral; HIV; Humans; Italy; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic; Species Specificity; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Proteins

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

We conducted a retrospective study of AIDS-associated cerebral toxoplasmosis. Eighteen patients received pyrimethamine plus sulfadiazine and 25 co-trimoxazole, with comparable baseline characteristics. There were no differences in clinical outcomes, but co-trimoxazole was better tolerated (p = 0.066). There was also a trend towards more deaths among patients who received glucocorticoids.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Kidney Diseases; Male; Pyrimethamine; Retrospective Studies; South Africa; Sulfadiazine; Toxoplasmosis, Cerebral; 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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoscopy; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hypoxia; Middle Aged; Oxygen Inhalation Therapy; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Radiography, Thoracic; Tomography, X-Ray Computed; 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

Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4.5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (>12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antifungal Agents; Female; Glucose; Humans; Hypoglycemia; Infant; Insulin; Male; Middle Aged; Pneumonia, Pneumocystis; Risk Factors; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination

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: Administration, Oral; AIDS-Related Opportunistic Infections; Amoxicillin; Anti-Infective Agents; Case Management; Child, Preschool; Disease Progression; Drug Resistance, Bacterial; Health Facilities; Humans; Infant; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury.. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children.. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose.. Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively.. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child, Preschool; Female; Humans; Infant; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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

We analyzed changes in plasma human immunodeficiency virus (HIV)-1 viral load, CD4+ T-cell count, and markers of immune activation markers at start of treatment of tuberculosis and 12 months after among 44 HIV-1-infected patients with newly diagnosed, sputum-smear positive for Mycobacterium tuberculosis pulmonary infection. All patients received a standard regimen of 6 months of rifampicin and isoniazid with first 2 months of pyrazinamid with or without cotrimoxazole. Compared with values at start of treatment, median viral load increased by a median of 0.64 log10 copies/ml after 12 months of follow-up (P=0.0002). Median CD4+ T-cell counts were 393 cells/L at start of treatment and 370 cells/L after 12 months of follow-up (P=0.61). Levels of serum activation markers decreased significantly at 12 months of follow-up of the patients for both patients on standard and cotrimoxazole treatment. Levels of viral load, CD4+ T-cell counts, and markers of immune activation were not different for patients on standard treatment of tuberculosis compared with those on standard and cotrimoxazole treatment. Levels of serum activation markers decreased significantly at 12 months of follow-up of the patients for both patients on standard and cotrimoxazole treatment. Because viral load is a predictor of disease progression, its persistent elevated levels in blood of HIV-infected patients co-infected with tuberculosis, who successfully complete TB treatment, may account for the high mortality observed in this population.

Topics: Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Biomarkers; CD4-Positive T-Lymphocytes; Cote d'Ivoire; Cytokines; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV-1; Humans; Male; RNA, Viral; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Viral Load

Topics: Adult; Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Developing Countries; Humans; Patient Selection; Pneumonia, Pneumocystis; 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

The aim of this study was to describe epidemiological, clinical, and bacteriological aspects of Escherichia coli bacteremia and meningitis in the Ibrahima-Diop-Mar infectious diseases clinic, Dakar Fann National Hospital Center (Senegal).. Data was collected from the bacteriology laboratory and hospitalization files.. 57 cases of E. coli bacteremia were reported. Among them, 10 were associated with meningitis. AIDS was diagnosed in 74% of the cases. The global lethality rate was 47% but this rate was higher in cases of associated meningitis (80 vs 37%) and in AIDS patients (50 vs 27%). Ceftriaxone, aztreonam, gentamicin, and ciprofloxacin were active on more than 95% of strains but cotrimoxazole was active on only 49% of the strains. Resistance to cotrimoxazole was higher among E. coli strains isolated from AIDS patients (62 vs 13%).. The low susceptibility to cotrimoxazole might increase the incidence of E. coli infections among patients with AIDS. It is therefore important to find an alternative to cotrimoxazole chemoprophylaxis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Bacteremia; Child; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Hospitals, Public; Humans; Male; Meningitis, Bacterial; Middle Aged; Retrospective Studies; Senegal; Systemic Inflammatory Response Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

To investigate the clinical characteristics, therapeutical approaches and outcome of Pneumocystis pneumonia (PCP) in patients with AIDS.. The clinical data of 22 PCP patients with AIDS who were treated in Peking Union Medical College Hospital from January 1992 to October 2004 were analyzed, including the routes of HIV infection, clinical profiles, immunological status, chest radiological characteristics, therapeutic managements and outcome.. (1) Of the 22 PCP patients, 16 were male and 6 female. The average age was (35.0 +/- 9.4) years old. The majority of patients got HIV infection through blood transfusion (54.5%) and sexual transmission (27.3%). (2) The common clinical presentations were fever (21/22), progressive exertional dyspnea (20/22), cough (16/22), sputum (12/22) and weight loss (18/22). 68.2% (15/22) of the patients had normal or mild coarse breath sounds on auscultation. 14 patients had an PaO(2) less than 60 mm Hg (1 mm Hg = 0.133 kPa). (3) All the 22 PCP cases were in their late stage of AIDS. For the 20 patients who had an immunological test, the peripheral CD(4)(+) T lymphocyte count was ranging from 3 x 10(6)/L to 148 x 10(6)/L and 90% of the cases had a CD(4)(+) T cell count less than 100 x 10(6)/L, 95% of the cases had a CD(4)(+)/CD(8)(+) ratio less than 0.20; (4) The most common abnormal chest radiological findings were bilateral diffuse interstitial infiltrations (19/22) and patchy shadows (14/22); (5) All patients were given trimethoprim-sulfamethoxazole (SMZco) and 86.4% of the patients were treated with corticosteroids concomitantly. Of the 22 PCP patients, 13 recovered, 5 gave up after knowing their definite diagnosis, 4 died. Comparing with the recovery patients, the 4 patients who died of PCP had much lesser CD(4)(+) T cell count (P = 0.07).. Most PCP occurred in patients who were in their late stage of AIDS and with a CD(4)(+) T cell count below 100 x 10(6)/L. For these reasons, we suggest that whenever encountering a young patient presenting with fever, dyspnea, hypoxia, loss of weight, the possibility of PCP complicating AIDS should be considered, especially when chest radiological study revealed interstitial infiltration or patchy shadows. If HIV was confirmed to be positive, the combined therapy of SMZco and corticosteroids should be started immediately.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Radiography, Thoracic; 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

Emergence of Staphylococcus aureus small colony variants (SCVs) has been associated with antibiotic use, particularly with trimethoprim-sulfamethoxazole (TMP-SMZ). In this study, 634 specimens of 125 patients with AIDS were prospectively screened for S. aureus with normal phenotype and for S. aureus SCVs. Charts of these patients were reviewed for previous prophylaxis with TMP-SMZ often used as long-term pneumocystosis prophylaxis. Thirty-seven patients (29.6%) harbored S. aureus in their anterior nares, three of these patients (8.1%) had S. aureus SCVs. Interestingly, TMP-SMZ does not appear to select for S. aureus SCVs in nasal swabs of these patients.

Topics: AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Colony Count, Microbial; Culture Media; Female; Humans; Male; Microbial Sensitivity Tests; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

This study of Pneumocystis carinii dihydropteroate synthase (DHPS) mutations in patients with AIDS who have P. carinii pneumonia compares the change in the prevalence of such mutations in the United States, where sulfa-drug prophylaxis is widespread, to that in China, where it is infrequent. The DHPS gene from 145 US patients presenting during 1983-2001 and from 15 Chinese patients presenting during 1998-2001 was amplified by polymerase chain reaction and was sequenced. In the United States, 40% of patients had DHPS mutations; 38% received sulfa-drug prophylaxis. Mutation prevalence increased to 70% during 2000-2001, from 25% during 1994-1995 (P<.01). In China, 7% of patients had DHPS mutations; none received sulfa-drug prophylaxis. The prevalence of P. carinii DHPS mutations has markedly increased in the United States but remains low in China.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; China; Dapsone; Dihydropteroate Synthase; Female; Humans; Male; Middle Aged; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; United States

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: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pneumonia, Pneumocystis; Risk Assessment; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients.. A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis.. 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses.. Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Antitubercular Agents; Female; HIV Seropositivity; Humans; Malawi; Male; Prospective Studies; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

PRESENTING FEATURES: A 53-year-old man who had human immunodeficiency virus (HIV) presented to the Johns Hopkins Hospital with a 3-month history of increasing dysphagia, cough, dyspnea, chest pain, and an episode of syncope. His past medical history was notable for oral and presumptive esophageal candidiasis that was treated with fluconazole 6 months prior to presentation. Three months prior to presentation, he discontinued his medications, and his symptoms of dysphagia recurred. During that time he developed intermittent fevers and chills, progressively worsening dyspnea on exertion, and a cough productive of white sputum. He also reported a 40-lb weight loss over the past 3 months. On the day prior to presentation, he had chest pain and shortness of breath followed by weakness, dizziness, and a brief syncopal episode. He denied orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, jaundice, hemoptysis, hematemesis, melena, hematochezia, or diarrhea. There was no history of alcohol use, and he stopped smoking tobacco approximately 1 month previously. He smoked cocaine but denied injection drug use. The patient had never been on antiretroviral therapy and had never had his CD4 count or viral load measured. On physical examination, the patient was a thin, cachectic man who appeared older than his stated age. His vital signs were notable for blood pressure of 102/69 mm Hg, resting tachycardia of 102 beats per minute, resting oxygen saturation of 92% on room air, normal resting respiratory rate, and a temperature of 38.1 degrees C. His oropharynx was clear, with no signs of thrush or mucosal ulcers. His pulmonary examination was notable for diminished breath sounds in the lower lung fields bilaterally. Cardiac, abdominal, and neurologic examinations were normal. His skin was intact, with no visible petechiae, rashes, nodules, or ulcers. Laboratory studies showed a total white blood cell count of 3.2 x 10(3)/microL, with a total lymphocyte count of 330/microL, hematocrit of 30.2%, a serum sodium level of 129 mEq/L, and a serum lactate dehydrogenase level of 219 IU/L. The patient had an absolute CD4 count of 8 cells/mm3 and a HIV viral load of 86,457 copies/mL. His arterial blood gas on room air had a pH of 7.51, a PCO2 of 33 mm Hg, and a PO2 of 55 mm Hg. Electrocardiogram and serial serum cardiac enzymes were normal. A chest radiograph showed bilateral upper lobe patchy infiltrates with left upper lobe consolidation. Computed tomographic (CT) scan o

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Chest Pain; Cough; Deglutition Disorders; Diagnosis, Differential; Drug Therapy, Combination; Dyspnea; Humans; Lung Diseases, Fungal; Male; Middle Aged; Pneumonia, Pneumocystis; Prednisone; Sporotrichosis; Syncope; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

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

Legionella infections are not frequent in HIV-infected patients, although clinical manifestations and outcome are particularly severe in this subset. This manuscript analyzes the clinical features and immunological situation of HIV-infected patients with Legionnaires' disease (LD).. The clinical files of HIV-infected patients diagnosed with LD from 1983 to December 2003 were reviewed. The incidence of hospital-acquired Legionella pneumonia (HALP) from 1997-2000 in HIV-infected patients was compared with that of non infected patients.. Eighteen patients were included. 72.2% were diagnosed by the Legionella urinary antigen assay. The incidence of HALP in HIV-infected and non infected patients was 0.3 and 0.25/1000 admissions/year, respectively (p = 0.42). 83.3% received appropriate antibiotic treatment at the Emergency department. The mean lymphocyte CD4 count was 348.1/microl, 53.8% had an undetectable viral load and 64.7% were on antiretroviral therapy. 72.2% were smokers, 38.8% had cancer and 16.7% were on chemotherapy. 93.8% had cough, 75% dyspnea, 62.5% extrarespiratory symptoms, 76.5% increased AST, 50% increased CK and 56.3% hyponatremia. Moreover, 50% developed bilateral pulmonary infiltrates, 83.3% respiratory failure and 22.2% died.. Although LD is not more frequent in HIV-infected than in non infected patients, its clinical severity suggests that it is an opportunistic infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Antigens; Comorbidity; Female; HIV Seropositivity; Hospitals; Humans; Incidence; Legionnaires' Disease; Male; 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

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

Topics: Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Evidence-Based Medicine; Humans; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

The aim of this study was to compare the type and antimicrobial resistance patterns of bacteria cultured from blood or respiratory tract secretions by HIV status and the use of trimethoprim-sulphamethoxazole (TMP-SMX) prophylaxis in children hospitalized with community-acquired pneumonia. During a 1-year prospective study in Cape Town, South Africa, 250 children [median aged 6 (3-16) months] hospitalized with pneumonia were enrolled; 151 (60.4 per cent) were HIV-infected. The incidence of bacteremia [35 of 244 cultures (14.3 per cent)] did not differ by HIV status. Bacteria were cultured in 17 of 32 (53 per cent) bronchoalveolar lavage specimens (BAL), 128 of 210 (61 per cent) induced sputa and 166 of 231 (71 per cent) nasopharyngeal specimens (NPAs). The type and number of bacteria in respiratory secretions did not differ by HIV status, except for a higher rate of Staphylococcus aureus in sputum or BAL [22 of 146 (15 per cent) vs. 3 of 96 (3 per cent), p = 0.003] and NPAs [41 of 135 (30 per cent) vs. 9 of 96 (9 per cent), p < 0.001] of HIV-positive children. The use of TMP-SMX prophylaxis in HIV-infected children was associated with an increased nasopharyngeal carriage of S. aureus [22 of 51 (43 per cent) vs. 17 of 79 (22 per cent), p = 0.009]. The rising prevalence of HIV infection and the use of TMP-SMX prophylaxis may alter the spectrum of colonizing and pathogenic bacteria in children in developing countries.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Bacteremia; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Infant; Pneumonia, Bacterial; Prospective Studies; Respiratory System; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred ninety-four bronchoalveolar specimens were evaluated by microscopic examination and by amplification of a sequence of a Pneumocystis carinii dihidropteroate synthase gene for identification of mutations linked to sulfa resistance. PCR sensitivity and specificity were 100 and 86.7%, respectively, compared to results of microscopic examination. However, 7 out of 19 microscopy-negative, PCR-positive samples were collected from subjects with a clinically high probability of P. carinii pneumonia, suggesting that PCR may be more sensitive than microscopic examination, although the absolute performance of PCR cannot be determined. Mutations were identified in 28 out of 70 (40%) PCR-positive specimens and were significantly more common in patients exposed to sulfa drugs (21 out of 29 [72.4%]) than in those not exposed to sulfa drugs (4 out of 35 [11.4%]).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Dapsone; Dihydropteroate Synthase; Drug Resistance, Fungal; Humans; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sensitivity and Specificity; 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

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

We present here the results of a survey conducted in Côte d'Ivoire, Africa, among healthcare providers, on the knowledge of prophylactic use of cotrimoxazole to prevent opportunistic infections in HIV-infected persons. The survey was conducted in 15 health centres, involved or not in the 'initiative of access to treatment for HIV infected people'. Between December 1999 and March 2000, 145 physicians and 297 other health care providers were interviewed. In the analysis, the health centres were divided into three groups: health centres implicated in the initiative of access to treatment for HIV-infected people with a great deal of caring for HIV-infected people, health centres implicated in this initiative but caring for few HIV-infected people, and health centres not specifically involved in the care of HIV-infected people. Six per cent of physicians and 50% of other health care providers had never heard of cotrimoxazole prophylaxis. The level of information about this prophylaxis is related to the level of HIV-related activities in the health centre. Among health care providers informed, knowledge on the exact terms of prescription of the cotrimoxazole is poor. In conclusion, it appears that the recommendations for primary cotrimoxazole prophylaxis of HIV-infected people did not reach the whole health care provider population. Most physicians are informed but not other health workers, even if the latter are often the only contact of the patient with the healthcentre. The only medical staff correctly informed are the physicians already strongly engaged in the care of HIV-infected people.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cote d'Ivoire; Drug Administration Schedule; Health Care Surveys; Health Knowledge, Attitudes, Practice; Health Personnel; HIV Seropositivity; Humans; Nurses; Physicians; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Homosexuality, Male; Humans; Male; Pneumonia, Pneumocystis; Secondary Prevention; Social Environment; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Hydrogen-Ion Concentration; Male; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral therapy, we describe a patient who developed recurrent PCP <3 months after discontinuing trimethoprim-sulfamethoxazole prophylaxis. He developed disease despite a sustained CD4 T-cell count above 200 cells/microL for more than 3 years while on antiretroviral therapy, as well as an apparent immune reconstitution against disseminated Mycobacterium avium complex (MAC) and Histoplasma capsulatum, for which he also discontinued therapy but without adverse effects. Thus, although increasing evidence continues to indicate that HIV-infected patients receiving combinations of antiretroviral therapies may regain specific immunity against opportunistic infections, our patient's experience suggests that this immune recovery may be selective and incomplete.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Humans; Male; Pneumonia, Pneumocystis; Secondary Prevention; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination

HIV-associated infections in sub-Saharan Africa differ markedly in their incidence from those in industrialized countries. Tuberculosis is the commonest cause of morbidity and mortality. Enteric pathogens such as microsporidiosis commonly cause disease as access to safe water is limited. Pneumocystis carinii pneumonia, which is the commonest opportunistic infection in industrialized countries, is uncommon in adults with HIV infection. This remains unexplained because P. carinii pneumonia is common in Black African HIV-infected children. Cytomegalovirus and Mycobacterium avium complex, which only occur in severely immune-suppressed individuals, are seldom found. One reason may be that survival after conversion to AIDS is relatively short in Africa. Patients often die before they develop severe immune suppression. Recently, prophylactic cotrimoxazole treatment was shown to be effective in symptomatic HIV-infected adults in Africa. Tuberculosis preventive therapy is also effective in Africa, at least in the medium term. It is hoped that these two affordable interventions will become available to large numbers of patients identified in voluntary counselling and testing centres.

Topics: Adult; Africa; Africa South of the Sahara; AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Black People; Child; Cytomegalovirus Infections; Developed Countries; Developing Countries; HIV Seropositivity; Humans; Incidence; Microsporidiosis; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

To report our experience in diagnosis and treatment of AIDS complicated by Pneumocystis Carinii Pneumonia (PCP), and explore the relations between preventive medication and occurrence as well as recurrence of PCP.. The clinical characteristics of 20 patients with AIDS complicated by PCP (identified from a cohort of 109 patients with AIDS) treated in our hospital during July 2000 to May 2002 were analyzed.. All the 20 cases had fever, 90 % of whom also had cough or expectoration, and chest radiography revealed bilateral interstitial changes in 80 % of the cases.. It is possible to diagnose PCP by typical clinical findings and chest X-ray, and compound sulfamethoxazole may prove effective for preventing the occurrence of PCP.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed.

Topics: Adult; AIDS-Related Opportunistic Infections; Cryptococcosis; Disease Progression; Drug Therapy, Combination; Fatal Outcome; Humans; Male; Pneumonia, Pneumocystis; Prednisone; Risk Assessment; Sepsis; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection. Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection. Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times. The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Brain; Dapsone; Diagnosis, Differential; Diagnostic Imaging; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Sulfadoxine; Survival Rate; Toxoplasmosis, Cerebral; 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

Pneumocystis jiroveci is a common cause of pneumonia in South African patients with AIDS. Sulphonamide resistance may become a problem in South Africa, as patients are treated with prophylactic co-trimoxazole when their CD4 counts fall below 200 cells/microliter. Failure of prophylaxis and treatment has been observed, possibly due to infection with sulphonamide-resistant strains. Sulphonamide resistance has been reported elsewhere, and is due to point mutations at codons 55 and 57 of the dihydropteroate synthase gene. Strain typing is useful for molecular epidemiological purposes.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Comorbidity; Drug Resistance, Bacterial; Humans; Pneumocystis; Pneumonia, Pneumocystis; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination

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

Highly active antiretroviral therapy (HAART) is responsible for a striking reduction in AIDS related morbidity and mortality by partly restoring immune function. However, HAART can also precipitate the development of clinically apparent opportunistic infections in patients with latent infections. We report a case of an HIV infected patient who developed granulomatous nodular and cavitatory lesions of the lungs due to Mycobacterium xenopi as a manifestation of the immune restoration syndrome.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Drug Combinations; Female; Humans; Immunocompromised Host; Lamivudine; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium xenopi; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.

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

Human infection with Nocardia species presents as a wide range of clinical syndromes. Nocardia is an important opportunistic pathogen in immunocom-promised patients. We report a case of primary Nocardia asteroides osteomyelitis as the initial clinical presentation of AIDS. The infection was successfully treated with a prolonged course of trimethoprim-sulfamethoxazole in conjunction with HAART. Nocardia osteomyelitis should be recognized as an unusual but important and treatable opportunistic infection in patients living with HIV infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Amikacin; Antiretroviral Therapy, Highly Active; Humans; Magnetic Resonance Imaging; Male; Nocardia Infections; Osteomyelitis; 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

Topics: Adult; Africa; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Health Planning Guidelines; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

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

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

Improvement in the immunological and virological profile of HIV-infected population during the era of highly active antiretroviral therapy (HAART), has allowed guidelines on discontinuation of Pneumocystis carinii pneumonia (PCP) prophylaxis to be published. A case of a 37-year-old homosexual man, who had sustained CD4 count over 200 cells/microl for 2 years while on secondary prophylaxis for PCP, who then developed PCP after cessation of prophylaxis, is presented. This case emphasizes the need for close monitoring of patients who discontinued secondary PCP prophylaxis with respiratory symptoms.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Little information exists on risk factors for Pseudomonas aeruginosa infection in persons with HIV. We assessed the incidence and factors associated with P aeruginosa among persons with HIV enrolled in a large observational cohort study in Los Angeles.. Data were analyzed from 4825 persons aged > or =13 years with HIV infection enrolled from 4 outpatient facilities from 1990 to 1998. The association between P aeruginosa infection and demographic, risk behavior, and clinical factors was assessed.. P aeruginosa was diagnosed in 72 (1.5%) patients representing a crude incidence rate of 0.74 per 100 person-years. The most frequent site of infection was pulmonary (47%). In multivariate analysis, prior hospitalization (adjusted rate ratio = 7.9, 95% CI, 3.8-16.2), and both dapsone (adjusted rate ratio = 4.0, 95% CI, 2.2-7.4) and trimethoprim-sulfamethoxazole (adjusted rate ratio = 2.5, 95% CI, 1.2-5.3) use were independently associated with higher rates of infection. Increasing days of inpatient stay (P <.01) and decreasing CD4(+) counts (P <.01) were strongly associated with P aeruginosa. Azithromycin use decreased the risk of infection by nearly 70%.. Although the overall observed incidence of P aeruginosa was low, hospital exposure, declining CD4(+) levels, and the use of dapsone or trimethoprim-sulfamethoxazole increased the risk of P aeruginosa disease, and azithromycin use was protective in this population. These findings may assist in the early recognition and diagnosis of persons likely to be at increased risk of P aeruginosa infection.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Cohort Studies; Cross Infection; Dapsone; Female; Health Behavior; Hospitalization; Humans; Incidence; Infection Control; Length of Stay; Los Angeles; Male; Middle Aged; Multivariate Analysis; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Risk-Taking; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Global Health; Health Services Accessibility; Humans; Incidence; Lung Diseases; Prevalence; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of acute respiratory failure due to Toxoplasma gondii mimicking pneumocystosis in an AIDS patient. Empirical antibiotic therapy with cotrimoxazole is discussed. Active research and identification of pathogens with adapted laboratory tests is mandatory.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Inflammatory Agents; Diagnosis, Differential; Humans; Lung Diseases, Parasitic; Male; Methylprednisolone; Respiratory Insufficiency; Toxoplasmosis; 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

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Female; HIV-1; Humans; Long-Term Care; Male; Pneumonia, Pneumocystis; Risk Factors; Sexually Transmitted Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Dapsone; Humans; Microbial Sensitivity Tests; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the proposed WHO/UNAIDS criteria for initiating co-trimoxazole prophylaxis in adult HIV-infected patients in Africa [WHO clinical stages 2--4 or CD4 count < 500 x 10(6) /l or total lymphocyte count (TLC) equivalent].. Observational cohort study of 5-year follow-up.. Adult HIV clinics, University of Cape Town, South Africa.. Effect of prophylactic low dose co-trimoxazole (480 mg per day or 960 mg three times per week) on survival and morbidity was assessed in patients stratified by WHO clinical stage, CD4 T-lymphocyte count or TLC. Patients receiving antiretroviral therapy were excluded.. Co-trimoxazole reduced mortality [adjusted hazard ratio (AHR), 0.56; 95% confidence interval (CI), 0.33--0.85; P > 0.001] and the incidence of severe HIV-related illnesses (AHR, 0.52; 95% CI, 0.38--0.68; P < 0.001) in patients with evidence of advanced immune suppression on clinical (WHO stages 3 and 4) or laboratory assessment (TLC < 1250 x 10(6)/l or CD4 count < 200 x 10(6)/l). No significant evidence of efficacy was found in patients with WHO stage 2 or CD4 count 200--500 x 10(6)/l/TLC 1250--2000 x 10(6)/l. If we had applied the WHO/UNAIDS recommendations 88.3% of our patients would have received co-trimoxazole prophylaxis at their initial clinic visit.. Co-trimoxazole in HIV-infected adults from an area in which Pneumocystis carinii pneumonia is uncommon demonstrated a survival benefit consistent with previous randomized trials. Further studies are needed to assess the optimal time of commencement of prophylaxis, as widespread co-trimoxazole use will lead to increasing antimicrobial resistance to other major pathogens in Africa.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cohort Studies; Female; Follow-Up Studies; Health Planning Guidelines; Humans; Male; Pneumonia, Pneumocystis; South Africa; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

We report the first case of HIV infection in a patient with underlying X-linked chronic granulomatous disease (CGD) who presented with hepatopulmonary nocardiosis. Despite the coexistence of CGD and HIV, the response to therapy was normal, and no unusual sequelae were noted. The patient's high virus burden was successfully repressed with antiretroviral therapy, suggesting that the nicotinamide adenine dinucleotide phosphate oxidase system is not essential for active viral replication or response to antiretroviral agents.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Granulomatous Disease, Chronic; Humans; Liver; Male; Nocardia; Nocardia Infections; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

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; Antibiotic Prophylaxis; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

To evaluate the WHO (World Health Organization) algorithm for management of respiratory tract infection (RTI) in HIV-1-infected adults and determine risk factors associated with RTI, we enrolled a cohort of 380 HIV-1-seropositive adults prospectively followed for incident RTI at an outpatient clinic in Nairobi, Kenya. RTI was diagnosed when patients presented with history of worsening or persistent cough. Patients were treated with ampicillin, or antituberculosis therapy when clinically indicated, as first-line therapy and with trimethoprim/sulfamethoxazole as second-line therapy. Five hundred ninety-seven episodes of RTI were diagnosed: 177 of pneumonia and 420 of bronchitis. The WHO RTI algorithm was used for 401 (95%) episodes of bronchitis and 151 (85%) episodes of pneumonia (p <.001). Three percent of bronchitis cases versus 32% of pneumonia cases failed to respond to first-or second-line treatment (p <.0001). Being widowed (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.0-4.4), less than 8 years of education (adjusted OR = 2.5, CI: 1.5 - 4.1), and CD4 count < 200 cells/microl (adjusted OR = 2.4, CI: 1.4-3.9) were risk factors for pneumonia. A high percentage of patients (32%) with pneumonia required a change in treatment from that recommended by the WHO guidelines. Randomized trials should be performed to determine more appropriate treatment strategies in HIV-1-infected individuals.

Topics: Adult; AIDS-Related Opportunistic Infections; Algorithms; Ampicillin; Bronchitis; Cohort Studies; Female; HIV-1; Humans; Kenya; Male; Odds Ratio; Pneumonia; Prospective Studies; Respiratory Tract Infections; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Two cases of acquired immunodeficiency syndrome with myelodysplasia are presented. Case 1 was admitted because of Pneumocystis carinii pneumonia. Mild anemia, thrombocytopenia and hypersegmented neutrophils were observed. After the administration of trimethoprim-sulfame-thoxazole and antiretroviral therapy, pancytopenia progressed. Bone marrow (BM) showed dysplastic hematopoiesis, suggesting human immunodeficiency virus-myelopathy. Case 2 was hospitalized due to progressive multifocal leukoencephalopathy. BM specimen obtained for thrombocytopenia showed myelodysplasia similar to myelodysplastic syndrome, suggesting that HIV may have an influence on hematopoietic progenitor cells.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bone Marrow; HIV-1; Humans; Male; Myelodysplastic Syndromes; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients.. We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs.. For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005).. These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Dihydropteroate Synthase; Drug Resistance, Microbial; Genotype; HIV-1; Humans; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Prognosis; Prospective Studies; Survival Analysis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; AIDS-Related Opportunistic Infections; Ampicillin; Anti-Infective Agents; Antitubercular Agents; HIV-1; Humans; Penicillins; Practice Guidelines as Topic; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination; World Health Organization

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed. We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2. The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose. There were no cases of proven or suspected PCP. Incidence of other serious bacterial infections was low. Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS. The drug is well tolerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Bacterial Infections; Child; Child, Preschool; Female; Humans; Incidence; Male; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Recurrent pneumococcal bacteremia receives infrequent mention in the literature, usually in association with patients who are immunocompromised.. To examine recurrent cases of pneumococcal bacteremia to determine risk factors and outcomes (mortality rates and emergence of resistance) associated with recurrences.. We retrospectively reviewed all cases of pneumococcal bacteremia identified by our microbiology laboratory from January 1, 1992, through December 31, 1996. Demographic, clinical, and laboratory data were abstracted.. There were 462 bacteremic episodes in 432 patients; 23 of these patients had 30 recurrent episodes. The 5.3% recurrence rate (23/432) is greater than that previously described. The median time to recurrence was 200 days. The mean age of patients with recurrences was 34 years, 70% were women, all were black or Hispanic (in near equal numbers), and 87% were infected with the human immunodeficiency virus (HIV). Human immunodeficiency virus infection, coexistent cancer, and female sex were independent predictors of recurrence. Only patients who were HIV-infected had multiple recurrences. Isolates from recurrent bacteremias were more likely to be penicillin-resistant than were initial bacteremic isolates (relative risk, 2.0; P =.16). Patients with recurrences had a higher (although not statistically significant) mortality rate than those without recurrences (22% vs 16%; P =.33). There was an inverse relationship between severity of illness and likelihood of recurrence.. Rates of recurrent pneumococcal bacteremia may be higher than previously reported. In patients with recurrent pneumococcal bacteremia, the presence of an underlying immunodeficiency should be investigated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Bacteremia; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Penicillin Resistance; Pneumococcal Infections; Recurrence; Risk Factors; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

To verify compliance with cotrimoxazole prophylaxis in human immunodeficiency virus (HIV) infected tuberculosis (TB) patients during the continuation phase of anti-tuberculosis treatment, and to assess the sensitivity, specificity and positive predictive values of verbal verification and pill counts as methods of checking compliance.. Cross-sectional study.. Cotrimoxazole compliance was assessed in a cohort of TB patients who were attending four TB follow-up centres during the continuation phase of anti-TB treatment between months 4 and 6. Verbal verification of drug intake, physical verification of pill count balance, and urine trimethoprim detection by gas chromatography and mass spectrometry were used for assessing compliance.. Using urine trimethoprim detection as the gold standard for compliance, trimethoprim was detected in 82 (94%) of 87 patients in the cohort. Verbal verification of cotrimoxazole intake and objective pill count balances showed high sensitivity and positive predictive values compared with the gold standard of urine trimethoprim detection.. In a rural district in Malawi, compliance with cotrimoxazole as an adjunct to anti-tuberculosis treatment in HIV-infected TB patients was good, and can be assessed simply and practically by verbal verification and pill counts.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Cohort Studies; Cross-Sectional Studies; Female; Gas Chromatography-Mass Spectrometry; Humans; Malawi; Male; Patient Compliance; Predictive Value of Tests; Rural Population; Self Administration; Sensitivity and Specificity; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

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; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Drug Resistance, Microbial; Humans; Malaria, Falciparum; Trimethoprim, Sulfamethoxazole Drug Combination

A case-control study to identify the risk factors for toxoplasmic encephalitis (TE) among HIV-infected patients with latent Toxoplasma gondii infection was performed in a teaching hospital in south-eastern Brazil. Although the subjects were all positive for serum IgG antibodies to Toxoplasma, some (the cases) developed TE during routine follow-up at the hospital whereas others (the controls) did not. Adjusted odds ratios (aOR) were estimated by multiple logistic regression after controlling for potential confounders. Only 46 (22%) of the 210 cases but 93 (45%) of the 205 controls were on prophylactic regimens with co-trimoxazole [aOR = 0.30; 95% confidence interval (CI) = 0.15-0.60]. Subjects with fewer than 100 (aOR = 37.09; CI =7.49-183.67) or between 100 and 200 CD4 cells/microl (aOR = 10.20; CI =2.00-51.90) were at substantially increased risk of developing TE than those with >400 CD4 cells/microl. Although the results of preliminary, unadjusted data analysis indicated that male sex and homosexual or bisexual activity might be additional risk factors, these associations were not found to be statistically significant by multiple regression analysis. In conclusion, no risk factors for TE other than low CD4 cell counts and failure to receive prophylaxis were found among HIV-infected Brazilian patients with past exposure to Toxoplasma. Seropositive patients with CD4 cell counts above 100/microl (the point at which specific prophylaxis is usually recommended) but below 200/microl might also benefit from effective anti-TE prophylaxis.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Case-Control Studies; CD4 Lymphocyte Count; Encephalitis; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Statistics as Topic; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.

Topics: AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Atovaquone; Dihydropteroate Synthase; Drug Resistance, Fungal; Fungal Proteins; Humans; Lymphoma, AIDS-Related; Male; Membrane Glycoproteins; Middle Aged; Mutation; Naphthoquinones; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Genotype; Humans; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; CD4 Lymphocyte Count; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Central Nervous System Fungal Infections; Drug Therapy, Combination; Fluconazole; Follow-Up Studies; Homosexuality, Male; Humans; Male; Pneumonia, Pneumocystis; Spinal Puncture; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The development of a rash in response to trimethoprim-sulfamethoxazole (TMP-SMX) administration is a frequent adverse reaction in people with the acquired immunodeficiency syndrome (AIDS). In contrast, there are no published reports in the English language literature describing TMP-SMX induced delirium in an AIDS patient. This report describes the development of frank delirium in a person with AIDS receiving TMP-SMX. The episode resolved completely within 72 h of withdrawal of the drug.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents; Delirium; Drug Therapy, Combination; Histoplasmosis; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; 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

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Bronchoalveolar Lavage Fluid; Dihydropteroate Synthase; Drug Resistance, Microbial; Female; Genes, Fungal; Humans; Japan; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sequence Analysis, DNA; Sulfonamides; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand.. HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort.. Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3-1.4; P= 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1-2.3; P = 0.47).. This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Outcome Assessment, Health Care; Pneumonia, Pneumocystis; Prospective Studies; Thailand; 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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Chemoprevention; Cote d'Ivoire; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

The spontaneous secretion in vitro of anti-Toxoplasma gondii antibodies by peripheral blood mononuclear cells was assessed in 69 patients with AIDS-related brain lesions. The sensitivity and specificity of this assay in the diagnosis of toxoplasmic encephalitis (TE) were found to be 85.4% and 92.8%, respectively. Twenty-four patients with TE were observed during 1-year follow-up after initiation of anti-Toxoplasma treatment and classified on the basis of their clinical and radiologic responses as sustained responders (SR; n = 11), incomplete responders (IR; n = 7) or transient responders (TR; n = 6). In vitro anti-T. gondii antibody secretion decreased as early as the first month after initiation of treatment and disappeared within the year in SRs, persisted in IRs, and decreased but rebounded at relapse in the TR patients. In vitro anti-T. gondii antibody, which reflects immune system activation by parasitic antigens, could be a surrogate marker of TE in AIDS patients.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Protozoan; Antiprotozoal Agents; Encephalitis; France; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

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

A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants.. All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated.. Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02).. PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Child, Preschool; Female; Humans; Infant; Lung; Male; Pneumocystis; Pneumonia, Pneumocystis; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Bacterial Infections; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; 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

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; 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

The results of multicenter clinical trials may differ across participating clinical sites. We present a diagnostic approach for evaluating this diversity that emphasizes the relationship between the observed event rates and treatment effects. We use as an example a trial of sequential strategies of Pneumocystis prophylaxis in human immunodeficiency virus infection with 842 patients randomly allocated to start prophylaxis with trimethoprim/sulfamethoxazole, dapsone, or pentamidine. Prophylaxis failure rates varied significantly across the 30 clinical sites (0-30.3%, p = 0.002 by Fisher's exact test) with prominent variability in the pentamidine arm (0-63.6%). Starting with oral regimens was better than starting with pentamidine in sites with high rates of events, whereas the three strategies had more similar efficacy in other sites. Sites enrolling fewer patients had lower event rates and had more patients who withdrew prematurely or were lost to follow-up. In a hierarchical regression model adjusting for random measurement error in the observed event rates, starting with trimethoprim/sulfamethoxazole was predicted to be increasingly better than starting with aerosolized pentamidine as the risk of prophylaxis failure increased (p = 0.01), reducing the risk of failure by 47% when the failure rate of pentamidine was 30%, whereas the two regimens were predicted to be equivalent when the failure rate was 17%. Differences in event rates could reflect a combination of heterogeneity in diagnosis, administration of treatments, and disease risk in patients across sites. The evaluation of clinical site differences with a systematic approach focusing on event rates may give further insight in the interpretation of the results of multicenter trials beyond an average treatment effect.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Controlled Clinical Trials as Topic; Dapsone; Humans; Multicenter Studies as Topic; Pentamidine; Pneumocystis Infections; Probability; Proportional Hazards Models; Sample Size; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Dapsone; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Failure; 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

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Florida; Haiti; Humans; Infant; Infant, Newborn; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To analyse the incidence of Pneumocystis carinii pneumonia after the withdrawal of prophylaxis, in patients with AIDS who were receiving HAART (highly active antiretroviral treatment).. Prospective opened study of 85 patients with AIDS (CD4 lymphocytes < 200 x 10(6)/l) and whose CD4 counts had increased over 200 x 10(6)/l after HAART, 79 were under primary prophylaxis and six secondary.. Mean CD4 lymphocytes count at the time of withdrawal was 343 x 10(6)/l. Mean time of follow-up after withdrawal was 358 days (range: 93-1,487; median: 302). None of the patients have had Pneumocystis carinii or toxoplasmosis after withdrawal of prophylaxis.. Pneumocystis carinii prophylaxis in AIDS patients might be safety withdrawn after effective HAART.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfones; 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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Liver Transplantation; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To study the clinical course and outcome of toxoplasmic encephalitis (TE) in patients with acquired immunodeficiency syndrome (AIDS).. Patients infected with human immunodeficiency virus (HIV) and neurological abnormality compatible with diagnosis of TE were enrolled in the study. These patients were treated with combination of trimethoprim/sulfamethoxazole and pyrimethamine. Response to therapy was assessed by clinical examination and repeat CT/MRI scan done after three weeks of starting treatment. Those showing response were put on prophylactic therapy.. A total of 451 patients of HIV infections were admitted to this centre during the study period, of these 11 patients were diagnosed to have TE. The common presenting symptoms were fever (80%), seizures (45%), headache (45%) and altered sensorium (25%). Focal neurological deficit was present in 80% of cases. Nine cases had ring-enhancing lesions on CT scan while in the remaining two patient's ring lesions were seen on MRI. These were either multiple (55%) or solitary (45%). Antitoxoplasma antibody was detected in 10 patients. It was absent in one patient. Ten patients had clinical and radiological improvement with trimethoprim/sulfamethoxazole and pyrimethamine within 10 +/- 3 days of starting therapy. One patient died within 10 days of starting therapy.. Toxoplasmosis is a common opportunistic infection of the central nervous system in patients with AIDS. Majority of patients with cerebral toxoplasmosis present with focal neurological abnormality in presence of characteristic neuroradiological abnormality and positive antitoxoplasma antibody titer. Response to empirical therapy helps to confirm the diagnosis, lifelong prophylaxis there after prevents relapse of potentially fatal and easily treatable condition.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Drug Therapy, Combination; Female; Humans; Male; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Bactrim/Septra is a drug used for treating and preventing PCP (Pneumocystis carinii pneumonia) and toxoplasmosis. However, people with HIV are more likely to develop hypersensitivity reactions to Bactrim/Septra. NAC (N-acetyl-cysteine) is being studied to determine if its detoxifying properties could reduce the risk of hypersensitivity to Bactrim/Septra. However, a Canadian study found no statistically significant difference in the rates of hypersensitivity among the nearly 200 subjects.

Topics: Acetylcysteine; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Free Radical Scavengers; Humans; Pneumonia, Pneumocystis; Primary Prevention; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

The Centers for Disease Control and Prevention (CDC) has determined that HIV-infected people are more likely to become infected first with Pneumocystis carinii pneumonia (PCP) than any other opportunistic infection. About 53 percent of people who died of AIDS between 1992 and 1997 had PCP. The symptoms of the disease are fever, cough, and breathing problems. PCP is thought to be spread through the air - and not through sexual transmission - so it is difficult to prevent exposure. There is no vaccine against PCP, so the most effective treatment is TMP-SMX, a drug which can prevent PCP. The effects and treatment of PCP in adults and children are described, and contact information is provided.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; CD4 Lymphocyte Count; Drug Hypersensitivity; Humans; Immunosuppressive Agents; Pneumonia, Pneumocystis; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antidotes; Drug Hypersensitivity; Glutathione; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Liver Function Tests; Pneumonia, Pneumocystis; Sinusitis; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; CD4 Lymphocyte Count; Community-Acquired Infections; Confidence Intervals; Cross Infection; Female; Humans; Karnofsky Performance Status; Length of Stay; Liver Cirrhosis; Logistic Models; Male; Odds Ratio; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Risk Factors; Smoking; Substance Abuse, Intravenous; Survival Analysis; 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-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Microbial; Humans; Male; Molecular Sequence Data; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Inventory of patients with a Mycobacterium kansasii infection.. Descriptive, retrospective.. Academic Medical Centre, Amsterdam, the Netherlands.. Review of the medical records of all patients with a bacteriologically confirmed infection with M. kansasii from January 1987 until the end of December 1996.. M. kansasii was isolated from 17 patients. Of 15 HIV-tested patients 13 were seropositive. Their median CD4 count was 10 x 10(6)/l. Ten HIV-positive individuals used trimethoprim-sulfamethoxazole prophylaxis. In 1 HIV-seropositive and in 1 HIV-seronegative patient no chest X-rays were made. Caverns were present in none of 12 HIV-positive patients and in 1 of 3 HIV-negative patients. Of the HIV-positive patients 1 fulfilled the criteria for pulmonary infection of the American Thoracic Society (ATS). According to these criteria 9 of the HIV-positive patients were colonized with M. kansasii. In 6 of these patients there were indications of infection: regression of pulmonary infiltrates with therapy (n = 3), positive histology and culture of lung tissue at autopsy (n = 1), and dissemination (n = 2). Disseminated infection occurred in a total of 4 HIV-infected patients.. HIV-infected patients are at an increased risk for M. kansasii infection. Trimethoprim-sulfamethoxazole does not offer protection against this infection. The diagnostic criteria of the ATS are not applicable to these patients. M. kansasii infection confirmed by isolation in an HIV-positive individual should always be treated.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Diagnosis, Differential; Disease Outbreaks; Female; HIV Seropositivity; Humans; Infection Control; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Netherlands; Retrospective Studies; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

Failures of prophylaxis against Pneumocystis carinii pneumonia (PCP) in AIDS patients do occur, but no evidence for drug resistance has yet been presented.. To determine whether mutations in the sulfa and sulfone drug target are associated with failure of prophylaxis using a sulfa-containing agent.. Portions of the gene for P. carinii dihydropteroate synthase (DHPS), the sulfa and sulfone target, from 27 patients (20 of whom had AIDS) diagnosed with PCP between 1976 and 1997 were amplified using polymerase chain reaction and sequenced. Seven of the 27 patients (all of whom had AIDS) were receiving sulfa or sulfone drugs as prophylaxis for PCP.. Mutations were found at only two amino-acid positions and were significantly more common in patients who received sulfa/sulfone prophylaxis. Mutations were observed in five (71%) out of seven isolates from AIDS patients receiving sulfa/sulfone as prophylaxis compared with only two (15%) out of 13 specimens from AIDS patients who did not (P = 0.022). No mutations were seen in isolates from seven non-HIV-infected patients, none of whom were on prophylaxis. Mutations were only observed in specimens obtained in 1995-1997.. Mutations in two amino-acid positions were significantly more common in AIDS patients with PCP who failed sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in both substrate and sulfa binding, based on homology to the Escherichia coli DHPS crystal structure. Thus, the results were consistent with the possibility that mutations in the P. carinii DHPS are responsible for some of the failures of sulfa/sulfone prophylaxis in AIDS patients.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Anti-Infective Agents; Child; Dapsone; Dihydropteroate Synthase; Drug Resistance, Microbial; Female; Humans; Infant; Male; Middle Aged; Mutation; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sequence Analysis, DNA; Treatment Failure; 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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Combinations; Female; Humans; Hyperkalemia; Hyponatremia; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Brain Neoplasms; Consciousness Disorders; Disease Susceptibility; Fatal Outcome; Hallucinations; Humans; Lymphoma, AIDS-Related; Male; Pneumonia, Pneumocystis; Psychoses, Substance-Induced; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To compare strategies for life-long prophylaxis of Pneumocystis carinii pneumonia (PCP) in a group of AIDS patients with a wide range of disease progression rates.. Markov decision models.. Prophylaxis strategies using high and low doses of trimethoprim-sulfamethoxazole (TS), dapsone, and/or aerosolized pentamidine in sequence, were compared. Efficacy and toxicity rates for prophylaxis regimens were taken from a meta-analysis of pertinent randomized controlled trials. Outcomes measured included lifetime episodes of PCP and drug toxicity per 100 patients treated, average life expectancy, and cost.. For patients with an expected survival of 3 years after commencement of prophylaxis, the use of standard or low dose TS as the first choice agent was comparable, and both were superior to the other strategies for preventing PCP (between nine and 26 fewer episodes of PCP per 100 patients treated) though they were more toxic (11-44 more episodes of toxicity per 100 patients treated). Life expectancy was similar for all of the treatment strategies. With slower rates of disease progression (expected survival > 3.8 years), as seen with current antiretroviral regimens, the use of low dose TS as the first choice agent dominated the use of standard dose TS; when the expected survival time was 7 years, initial use of low dose TS led to 2.8 fewer episodes of PCP per 100 patients treated, 32 fewer episodes of toxicity per 100 patients treated, and US$1381 per patient lower cost, compared with prophylaxis with standard dose TS.. For patients with AIDS and expected survival > 3.8 years, low dose TS is better than standard dose TS as the first choice agent for preventing PCP. As patients with AIDS live longer, the routine use of low dose TS will be more than adequate for patients at risk for PCP.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Disease Progression; Drug Costs; Health Care Costs; Humans; Life Expectancy; Markov Chains; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of Pneumocystis carinii pneumonia in a patient with acquired immunodeficiency syndrome diagnosed and monitored with polymerase chain reaction (PCR) for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan (G-test). Results of both studies paralleled the clinical and radiographic improvement. However, the plasma (1-->3)-beta-D-glucan level remained higher than normal when PCR for Pneumocystis carinii became negative in sputum. Both PCR for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan are useful for noninvasive diagnosis and monitoring of Pneumocystis carinii, although further investigation is necessary to quantify their relationship.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; beta-Glucans; Glucans; Glucocorticoids; Humans; Male; Methylprednisolone; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Radiography, Thoracic; Sputum; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE).. we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks.. 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity.. TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Retrospective Studies; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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 monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia.. Trimethoprim-sulfamethoxazole steady-state plasma concentrations were measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15-23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range.. Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7%. Monitoring of co-trimoxazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with chronic liver disease or renal failure.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chromatography, High Pressure Liquid; Chronic Disease; Drug Monitoring; Female; Humans; Kidney; Liver Diseases; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; 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

We studied fecal colonization with vancomycin-resistant enterococci (VRE) in 89 HIV-infected nonhospitalized patients ages 24 to 62 years, including 70 (79%) men (including 41 homosexual and 5 bisexual men) and 19 (21%) women. Of the 89 patients, 61 (69%) were black, 25 (28%) Hispanic, and 3 (3%) white; 53 (60%) had history of ongoing or recent antibacterial therapy with trimethoprim/sulfamethoxazole (29), clarithromycin (18), amoxicillin (7), ofloxacin (3), and metronidazole, doxycycline, dicloxacillin, and cephalexin (1 each). VRE were not isolated from any of the patients studied.

Topics: Adult; AIDS-Related Opportunistic Infections; Amoxicillin; Anti-Bacterial Agents; Bisexuality; Black People; Cephalexin; Cephalosporins; Clarithromycin; Dicloxacillin; Doxycycline; Drug Resistance, Microbial; Enterococcus; Feces; Female; Gram-Positive Bacterial Infections; Homosexuality, Male; Humans; Male; Metronidazole; Middle Aged; Ofloxacin; Penicillins; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; White People

In this paper, the authors present an evaluation algorithm for systematic assessment of the observed heterogeneity in disease risk within trial populations. Predictive models are used to estimate the predicted patient hazards, the odds of having an event in the upper risk quartile (ODU) and the lower risk quartile (ODL), and the odds ratio (rate ratio for time-to-event analyses) for having an event in the upper risk quartile versus the lower risk quartile (extreme quartile odds ratio (EQuOR) and extreme quartile rate ratio (EQuRR)). The ranges for these metrics depend on the extent to which predictors of the outcome of interest exist and are known and the extent to which data are collected in the trial, as well as on the eligibility criteria and the specific patients who are actually enrolled. ODU, ODL, and EQuOR values are used to systematically interpret the results for patients at different levels of risk, to evaluate generalizability, and to determine the need for subgroup analyses. Individual data for five outcomes from three trials (n = 842, 913, and 1,001, respectively) are used as examples. Observed EQuOR values ranged from 1.5 (very little predicted heterogeneity) to 59 (large heterogeneity). EQuRR values ranged from 2 to 46. ODU values ranged from 0.24 to 3.19 (generally high risk), and ODL values ranged from 0.01 (clinically negligible risk) to 0.16 (clinically meaningful risk). The algorithm may also be used for comparing diverse trials (e.g., in meta-analyses) and used prospectively for designing future trials, as shown in simulations.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Algorithms; Anti-HIV Agents; Bias; Dapsone; Humans; Meta-Analysis as Topic; Models, Statistical; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Research Design; Risk; Survival Analysis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Our objective was to examine the accuracy of diagnosis of HIV-associated central nervous system (CNS) toxoplasmosis. Individuals diagnosed with HIV-associated CNS toxoplasmosis and controls were ascertained from a population-based database. Diagnosis was confirmed by response to therapy or by histology. Symptoms, results of anti-Toxoplasma serology and use of Pneumocystis carinii pneumonia (PCP) prophylaxis were recorded. Central nervous system toxoplasmosis was confirmed in 54 (76%) of 75 patients. Reactive anti-Toxoplasma serology was associated with CNS toxoplasmosis (OR=20.4, 95% CI 3.1-175.8). Adjusting for CD4 and use of dapsone or aerosolized pentamidine, trimethoprim-sulphamethoxazole (TMP-SMX) for PCP prophylaxis was associated with lower likelihood of CNS toxoplasmosis (OR 0.3, 95% CI 0.1-0.7). Diagnosis of CNS toxoplasmosis is often incorrect. Another diagnosis is most likely in patients who are anti-Toxoplasma seronegative or who are receiving prophylactic TMP-SMX.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; False Positive Reactions; Humans; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of successful desensitization to dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis in a patient unable to tolerate trimethoprim/sulfamethoxazole (TMP/SMX) desensitization or dapsone at standard doses.. A 37-year-old HIV-positive African-American man was treated for pneumonia with TMP/SMX and then continued on the drug for PCP prophylaxis. After experiencing a pruritic maculopapular rash with TMP/SMX, both at standard doses and after attempting a desensitization regimen to the drug, he was started on dapsone for PCP prophylaxis. He experienced a rash and fever after taking dapsone at standard PCP prophylactic doses. At this time, an 18-day oral dapsone rechallenge by dose escalation was attempted, and it was well tolerated.. This case suggests that utilization of a dapsone desensitization regimen may permit a viable treatment option in patients previously thought to be intolerant to the agent. More regimens of this type should be attempted and the results published, using both dapsone and TMP/SMX, so that standard desensitization treatment guidelines may eventually be adopted.

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

Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown.. We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk.. We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias.. There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Odds Ratio; Pentamidine; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Retrospective Studies; Risk; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A case of cotrimoxazole-induced meningoencephalitis in an HIV-infected patient without signs of AIDS is reported. The patient developed an apparently generalized seizure, of cotrimoxazole, 1 month after first taking a dose of this drug and a febrile coma after a second dose 3 weeks later. Lumbar puncture revealed eosinophilic aseptic meningitis. The patient quickly recovered without sequelae and was given antiretroviral therapy plus pentamidine aerosolized and pyrimethamine as prophylaxis for opportunistic infections. No other adverse effects were observed. The report describes the diagnosis of this case supported by a commentary, including a literature review.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Eosinophilia; Humans; Male; Meningitis, Aseptic; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced hyperkalemia is an important but often overlooked problem encountered commonly in clinical practice. It may occur in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient should include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. Medications generally produce hyperkalemia either by causing redistribution of potassium (beta2 -adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by (1) interfering with the production and/or secretion of aldosterone (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or (2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal insufficeiency is generally required to cause hyperkalemia, an elevated serum potassium concentration in a patient with mild-to-moderate renal failure should not be ascribed to renal failure alone. A careful search for "hidden" potassium loads and for causes of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is important to recognize that the causes of hyperkalemia may be additive. Patients may have more than one cause of hyperkalemia at the same time. Therefore, all potential causes of hyperkalemia, including drugs, should be systematically evaluated in every hyperkalemic patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Aldosterone; Anti-Infective Agents; Diagnosis, Differential; Electrocardiography; Fluid Shifts; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Potassium; Tissue Distribution; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Pneumonia, Pneumocystis; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Complicated regimens can lead to adherence problems when they include protease inhibitors and anti-PCP medications. A study of 244 adults showed that adherence was not a factor of age, race, gender, or class but was related to the number of times per day a medication was taken, the belief that the medications would work, the patient's positive mental health, and whether friends or family members would remind patients about taking their medications. Researchers need to address adherence issues in an effort to stop the development of drug resistant viruses.

Topics: AIDS-Related Opportunistic Infections; Dapsone; Humans; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Three studies that are highlighted suggest that PCP-causing microbes are developing resistance to Bactrim/Septra (B/S), the drug of choice for preventing the life-threatening complications caused by PCP, toxoplasmosis, and bacterial pneumonia. While resistance does not appear to be happening on a large scale, it is a concern because no other drug has the same beneficial effects of B/S. Research is needed for simple, low-toxicity treatments and prophylactic drugs for PCP, before resistance becomes a common problem.

Topics: AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Drug Resistance, Microbial; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (Bactrim) has been shown effective in preventing most of the opportunistic infections (OIs) prevalent in Western Africa. Reductions of OIs mortality by 48 percent and hospitalizations by 44 percent are reported from one cotrimoxazole trial. It is suggested that there is a great need for basic prophylactic treatment of OIs in Africa, since access to antiretrovirals there is limited. Cotrimoxazole is much cheaper than a course of antiretrovirals, which is a great benefit.

Topics: AIDS-Related Opportunistic Infections; Cote d'Ivoire; Drug Costs; Drug Resistance, Microbial; Health Services Accessibility; Humans; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Using results of a multicentric randomized prospective trial of primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients which compared sulfamethoxazole-trimethoprim and pentamidine isethionate, the risk to develop cerebral toxoplasmosis was analyzed in the two assigned groups and in the groups of patients who stopped sulfamethoxazole-trimethoprim prophylaxis. The risk to develop cerebral toxoplasmosis appeared significantly higher in the group of patients who stopped sulfamethoxazole-trimethoprim consecutively to cutaneous hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Drug Eruptions; Drug Therapy, Combination; Follow-Up Studies; Humans; Multicenter Studies as Topic; Pentamidine; Pneumonia, Pneumocystis; Probability; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Survival Rate; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

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

The records of patients in whom Pneumocystis carinii pneumonia (PCP) was diagnosed between January 1989 and December 1991 were reviewed. Thirty-two patients--all immunocompromised--were included in the study: 41% were HIV-positive and 59% HIV-negative. In 23 patients (72%) concomitant pathogens were isolated, most frequently Cytomegalovirus. Presenting symptoms included fever (97%), cough (75%) and dyspnea (63%). All HIV-infected patients had a T4-lymphocyte count below 200/mm3 (or 20%). The majority of patients (80%) treated with trimethoprim-sulfamethoxazole experienced adverse events which were usually well tolerated so that a therapy change was necessary in only 12% of patients. PCP was fatal in 34% of the patients. Respiratory failure requiring mechanical ventilation carries a poor prognosis. The ratio of non-AIDS/AIDS patients infected with PC is increasing. This increase is due to the growing contribution of patients treated with immunosuppressive agents and patients with disease-associated immunodeficiencies other than AIDS. Our study suggests that treatment of PCP is more successful with early diagnosis. In addition, as mortality rate is high in non-AIDS patients, our data suggest that the more frequent use of PCP prophylaxis in patients given immunosuppressive drugs, might reduce the incidence of PCP and PCP related mortality.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; HIV Seropositivity; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the influence of empiric treatments prior to fiberoptic bronchoscopy (FOB) on the diagnostic yield of BAL in HIV-positive patients with respiratory symptoms.. We studied 123 consecutive FOBs with BAL in HIV-positive patients; 101 of these patients (82%) had received previous antimicrobial treatment from 1 to 60 days. Diagnostic yield of BAL for Pneumocystis carinii, Mycobacterium tuberculosis, and bacterial pneumonia was compared between patients with and without previous empiric treatments.. A diagnosis was obtained in 85 patients (69%), of whom 17 (20%) had multiple infections. Diagnostic yield was higher in patients without previous treatment, 91% (20/22) compared with 64% (65/101), p < 0.03. Diagnostic yield was also higher for bacterial pneumonia: seven isolations from 22 patients not receiving previous empiric treatment (32%), compared with 11 of those who had (11%; p < 0.02). The duration of empiric treatment against P carinii in patients in whom it was isolated was significantly shorter than in those in whom P carinii was not detected (3.5 +/- 1.8 days compared with 5.2 +/- 2.4 days; p = 0.003). FOB permitted a change in treatment in 62% of patients with a final diagnosis.. This study demonstrates that empiric treatments prior to FOB significantly impair the diagnostic yield of BAL in detecting common pathogens in HIV-infected patients with respiratory symptoms.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antitubercular Agents; Bacteria; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cytomegalovirus; Cytomegalovirus Infections; Female; Fiber Optic Technology; Herpes Simplex; Humans; Length of Stay; Lung Diseases; Male; Middle Aged; Mycobacterium tuberculosis; Pentamidine; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Simplexvirus; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Adverse drug reactions to trimethoprim-sulfamethoxazole (TMP/SMX) are common in HIV-positive patients. However, only one case of TMP/SMX-related rhabdomyolysis has been reported, so far. We report a 55-year old-man with asymptomatic rhabdomyolysis after oral high-dose TMP/SMX for suspected PCP. Laboratory changes settled after discontinuation of the drug.

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

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Bacteria; Cote d'Ivoire; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clinical Trials as Topic; Dapsone; Data Collection; Data Interpretation, Statistical; Databases, Bibliographic; Humans; Information Storage and Retrieval; Meta-Analysis as Topic; Multivariate Analysis; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Selection Bias; Trimethoprim, Sulfamethoxazole Drug Combination

Adolescents infected with the human immunodeficiency virus (HIV) often confront the clinician with difficult medical problems. Besides the host of opportunistic infections, which can affect these patients, side effects from medications can be frequent and, at times, life-threatening. We report a case of aseptic meningitis secondary to trimethoprim-sulfamethoxazole therapy for prophylaxis against Pneumocystis carinii in an HIV-infected adolescent.

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

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bacteremia; Female; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Imipenem; Male; Nocardia Infections; Thienamycins; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A population pharmacokinetic model of intravenously and orally administered trimethoprim in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia has been made using a parametric iterative two-stage Bayesian and a nonparametric expectation maximization computer program. When good information was present in the serum level data, both methods obtained similar results. With the nonparametric expectation maximization program, the median apparent rate constant for absorption (Ka) was 1.602 hr-1, median slope (Ks) of the relationship between creatinine clearance and elimination was 0.001168 hr-1, median apparent volume of distribution (Vs) was 1.058 l/kg, and median fraction of oral dose absorbed (Fa) was 0.955. These results permit dosage individualization adjusted to body weight and renal function to achieve chosen serum level peak and trough goals. Peak goals of 9 ug/ml and trough goals of 5 ug/ml appear reasonable for most patients in this population, and should permit most to complete an effective course of therapy with a reduced risk for treatment-terminating hematologic toxicity. However, therapeutic goals should always be selected based on each patient's apparent need for the drug and the risk of toxicity that is justifiably acceptable to obtain the expected benefits of the drug.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bayes Theorem; Drug Monitoring; Humans; Injections, Intravenous; Models, Biological; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the association between trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis carinii pneumonia and risk of bacterial infections in persons with AIDS, we abstracted hospital records from 6496 adult admissions to 42 hospitals in western Washington state. Of these admissions, 570 involved 637 bacterial infections diagnosed among patients who had been prescribed prophylactic TMP-SMX or aerosolized pentamidine. Cases [admissions with bacteraemia, bacterial pneumonia, acute or chronic sinusitis, or urinary tract infection (UTI)] were compared to controls (admissions not associated with any of the 5 bacterial infections). After adjusting for CD4 lymphocyte count and presence of P. carinii pneumonia, TMP-SMX prophylaxis, relative to aerosolized pentamidine prophylaxis, was associated with a reduced risk of bacteraemia (adjusted OR = 0.5; 95% CI, 0.2-1.0; P = 0.04), bacterial pneumonia (adjusted OR = 0.5; 95% CI, 0.3-0.8; P = 0.01), acute sinusitis (adjusted OR = 0.5; 95% CI, 0.2-1.3; P = 0.2), chronic sinusitis (adjusted OR = 0.3; 95% CI, 0.1-0.7; P = 0.01), and UTI (adjusted OR = 0.5; 95% CI, 0.2-1.2; P = 0.1), and all 5 bacterial infections combined (adjusted OR = 0.6; 95% CI, 0.5-0.8; P < 0.001).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bacterial Infections; Case-Control Studies; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Pentamidine; Registries; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Drug Therapy, Combination; Humans; Hyperglycemia; Methylprednisolone; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetylation; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Phenotype; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; Humans; Male; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; 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

The estate of [name removed] will receive a $75,000 emotional distress award in addition to $104,109 in emotional damages from Dr. [name removed], [name removed], an infectious disease specialist. [Name removed] suffered an allergic reaction to Cotrim, a sulfa-based medicine prescribed by Dr. [name removed]. The reaction resulted in [name removed]'s hospitalization and eight months of recovery. [Name removed]'s allergy to sulfa-based drugs was noted on his chart. [Name removed]'s attorney argued that [name removed] was already in a frail emotional state and thus should not be entitled to full recovery of emotional distress damages. In 1995, the State Court of Appeals ruled that the damage award should go back to court. The Supreme Court turned down [name removed]'s request and restored the damage award.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Fluoroquinolones; Humans; Male; Malpractice; Medical Records; Oregon; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Research results to determine the best prophylactic regimen for Pneumocystis carinii pneumonia (PCP) are reported. Overall results from these studies indicate patients who are eligible for PCP prophylaxis should be advised to take double-strength trimethoprim/sulfamethoxazole (TMP/SMX) on a daily basis, a dosage found more effective than thrice-weekly. To handle problems with side effects, one study demonstrated the success of using a 6-day dose escalation method that allowed 80 percent of the participants to complete treatment for 6 months. Patients remaining intolerant to TMP/SMX have the options of using atovaquone (not yet FDA-approved for PCP prophylaxis) or aerosolized pentamidine (not approved for treatment of PCP), which have been shown to be safe and effective in PCP prophylaxis. Due to recent FDA reforms, the use of off-label drugs may increase, but patients and physicians are cautioned that problems with insurance reimbursement may develop.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; CD4 Lymphocyte Count; Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Encephalitis; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effectiveness of primary prophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection.. We conducted a retrospective analysis of a cohort of infants followed from birth at six metropolitan hospitals and one outpatient clinic for pregnant, drug-using women in New York City. Outcomes measured were histologically confirmed PCP and/or death. The potential confounding effect of the infant's stage of illness, as determined by CD4 count, was controlled by including all CD4 determinations as time-dependant covariates in a Cox proportional hazards analysis. Cases were censored at PCP onset, death, loss to follow-up, and 18 months of age.. One hundred twelve HIV-infected children were enrolled at birth between 1986 and 1993. Sixty of these were tracked beyond 18 months of age; of the others, 21 died before this age, 4 were considered lost to follow-up, and 27 had not reached 18 months of age at the last visit. Only 3 cases (4%) of confirmed PCP occurred among the 70 children who received primary PCP prophylaxis before 18 months of age, compared with 12 cases (28%) among 42 children not receiving PCP prophylaxis at any point before 18 months of age. The Kaplan-Meier estimated incidence of PCP in the first year among children not receiving prophylaxis was 25% (95% confidence interval [CI], 12 to 39). Using Cox methods, the unadjusted risk of PCP among infants not receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to 15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the absolute number of CD4-positive cells. Eight of 26 deaths were caused by PCP, and the likelihood of early death was significantly diminished if PCP prophylaxis was given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to 6.1).. We report evidence that primary antimicrobial PCP prophylaxis is highly effective in decreasing the frequency of PCP and early death in infants with perinatal HIV infection. These findings support the revised National Pediatric HIV Resource Center and Centers for Disease Control and Prevention guidelines for PCP prophylaxis in children.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Female; Follow-Up Studies; Humans; Incidence; Infant; Pneumonia, Pneumocystis; Pregnancy; Primary Prevention; Proportional Hazards Models; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

In hospitals attended by patients with human immunodeficiency virus infection, adverse reactions are often observed to trimethoprim-sulfamethoxazole, particularly cutaneous reactions. Given the importance of this drug for prophylaxis we have attempted to establish a desensitization or tolerance protocol so that patients can continue the drug without repeated adverse reactions.. We studied 34 HIV patients with adverse cutaneous reactions to trimethoprim-sulfamethoxazole, slight to moderate in nature but not life-threatening. Skin tests (prick and intradermal) were done in an attempt to rule out a mechanism of hypersensitivity. Subsequently, trimethoprim-sulfamethoxazole was administered orally in increasing doses beginning with trimethoprim, 0.2 mg, and sulfamethoxazole, 1 mg. The same dose was repeated after 12 hours and then doubled every 24 hours until the therapeutic dose was achieved. If adverse reactions appeared we maintained the last dose administered and administered antihistamines until the reactions cleared or improved.. None of the patients had positive skin tests (immediate or delayed). Twenty- seven patients were satisfactorily desensitized. After a follow-up of 3 months, 25 patients were still incident-free on trimethoprim-sulfamethoxazole prophylaxis, and 19 returning for check-ups at 6 months could still tolerate the drug well.. Our data indicate that patients with adverse reactions to trimethoprim-sulfamethoxazole can continue prophylactic treatment after oral desensitization.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Male; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; HIV; HIV Seropositivity; Humans; Male; Pneumocystis Infections; Rhabdomyolysis; Trimethoprim, Sulfamethoxazole Drug Combination

Eighty initial episodes of HIV-associated Pneumocystis carinii pneumonia (PCP) diagnosed at Bordeaux hospital between 1985 and 1993 are reported (57 were men and 23 women). PCP revealed HIV infection in 29 patients (36%). Others cases were patients with poor medical follow up (10%), with a CD4+ lymphocyte count above 200/mm3 at last follow-up (9%), non compliant with PCP prophylaxis (9%), or using aerolized pentamidine (AP+) (20%). The main clinical symptoms were fever (90%), dyspnea (68%), non productive (63%) and productive (17%) cough. Radiographic infiltrates were purely interstitial (59%), acinar and interstitial (25%), purely acinar (5%) and absent (11%). Thirty-eight percent of AP+ had upper lobe preferential involvement and 13% a pleural effusion. In all cases, Pneumocystis carinii was detected in bronchoalveolar lavage. Extrapulmonary localizations of pneumocystosis were noticed (eye, liver, spleen, ascitis) in two AP+. Mean CD4+ count was 54/mm3 in patients not having received aerolized pentamidine (AP-) and 22/mm3 in AP+. P24 antigenemia was positive in 53% (AP-) and 88% (AP+). PaO2 LDH and albuminemia were similar in both groups. Antimicrobial therapy (Cotrimoxazole in 91% of the cases) was combined with corticosteroids in 45% and mechanic ventilation in 19%. After 30 days of follow-up, 17 deaths were observed (21%) and 14 attributed to PCP: mortality was worse in AP+ (31%) than in AP- (19%). The main conclusions of our study are the followings: HIV related PCP is still in 1995 frequent and severe; atypical features should not rule out diagnosis; preventive measures are neither sufficient nor efficient. PCP remains in 1995 a priority in HIV related public health and therapeutical research.

Topics: Adult; Aerosols; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Recurrence; Retrospective Studies; Serum Albumin; Time Factors; 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

Severe cellular immunosuppression developed in a 25-year-old man with hemophilia B who was infected with the human immunodeficiency virus (HIV). Four days after administration of sulfamethoxazole-trimethoprim (SMX-TMP) for prophylaxis against Pneumocystis carinii pneumonia (PCP), diffuse uptake of both lungs was confirmed on a 67Ga scintigram. Reticular shadows were also seen throughout both lung fields on a chest CT scan. These findings were compatible with PCP, according to the guidelines for presumptive diagnosis of the acquired immunodeficiency syndrome, published by the Centers for Disease Control and Prevention. The dose of SMX-TMP was increased, but interstitial pneumonitis worsened and was accompanied by fever, skin rash, and liver dysfunction, which are common in HIV-infected patients receiving SMX-TMP. No evidence of PCP or of any other opportunistic infection was found by bronchoalveolar lavage. Adverse reactions diminished after SMX-TMP administration was stopped. The 67Ga scintigram and chest CT findings also returned to normal. We concluded that the interstitial pneumonitis was induced by SMX-TMP. SMX-TMP is the first choice anti-PCP drug, but a high incidence of adverse reactions in patients with HIV infection has been reported. Therefore the possibility of SMX-TMP-related pulmonary toxicity must be considered in HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Diagnosis, Differential; Drug Therapy, Combination; Hemophilia B; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Desensitization, Immunologic; Humans; Male; Pneumonia, Pneumocystis; 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

Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX).. Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1.. Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005).. Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Cohort Studies; Female; Hodgkin Disease; Humans; Male; Pneumonia, Pneumocystis; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uric Acid

To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons.. Medical facility-based prospective medical record reviews of consecutive patients.. We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX).. The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease.. Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The prognosis of first episodes of HIV-associated PCP has markedly improved. The knowledge about the reasons for this progress could bear important implications for the management of HIV-infected patients.. Clinical and laboratory parameters, as well as therapy and clinical course were documented. Prognostic analysis was performed using a logistic regression model. Early (1985-1988) and late (1989-1994) episodes were compared with regard to the results of the prognostic analysis.. 67 patients (61 male, six female, mean age 35 +/- 12 years) without any prophylaxis presenting with a first episode of PCP were treated from 1985 until 1994. 95% of patients had a known HIV-serostatus prior to the diagnosis of PCP. Hemoglobin, percentage of neutrophils in BALF as well as AaDO2 were variables significantly associated with lethal outcome. The prognosis of late episodes was significantly improved (7 versus 32% lethal outcomes, log rank p < 0.01). AaDO2 as the only parameter found to be significantly associated with outcome was significantly lower in the late episodes, accordingly. The mean time until diagnosis of PCP was five days shorter in this group. Moreover, CD8 cell-count and serum albumin were found to be significantly higher, and mean loss of weight prior to diagnosis of PCP significantly lower.. The prognosis of first episodes of PCP without any prophylaxis is most closely associated to the severity of pneumonia as reflected by AaDO2. Causes for a minor severity of PCP include an earlier diagnosis as well as better immunity and a better clinical performance at the time of PCP. The improved prognosis therefore results from the experience of the treatment center. A known HIV-serostatus and regular medical care by an experienced treatment center contributes significantly to improved outcome of PCP also in the group non-compliant to distinctive recommendations with regard to prophylaxis for PCP.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Cause of Death; Eflornithine; Female; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiratory Function Tests; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Insufficiency; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Seropositivity; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To study the outcome of a modified oral desensitization protocol for trimethoprim-sulfamethoxazole in human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and acquired immune deficiency syndrome.. A prospective study.. Tertiary care referral center.. Thirteen human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and allergy to sulfonamides who failed alternative therapy.. Oral desensitization to trimethoprim-sulfamethoxazole.. Nature of allergic reactions, toxicity of alternate medications, indication as well as outcome of trimethoprim-sulfamethoxazole desensitization and routine laboratory determinations.. The most common reaction to trimethoprim-sulfamethoxazole was generalized, pruritic maculopapular rash (n = 10, 76.9%) followed by urticaria/angioedema in two patients (15.38%). Two patients had generalized pruritus without rash. All patients (n = 13) tolerated oral desensitization to trimethoprim-sulfamethoxazole without any adverse reactions including three patients who were critically ill and on mechanical ventilation. Thus the success rate of our protocol was 100%. No patient had received antihistamines prior to or during the protocol. Four patients (5, 6, 7, and 9) were receiving prednisone for severe Pneumocystis carinii pneumonia. Total followup has ranged from 4 to 84 weeks. Two patients died during followup due to causes unrelated to desensitization. All other patients are tolerating trimethoprim-sulfamethoxazole without any allergic reactions.. Oral desensitization to trimethoprim-sulfamethoxazole, as per this protocol is safe, in that there were no systemic or cutaneous reactions during desensitization as well as followup. It is well tolerated in all patients, including the three critically ill patients. As judged by the outcome and ability to tolerate trimethoprim-sulfamethoxazole after desensitization, the procedure is successful in all patients in this study. Equipped with this protocol one can evaluate possible mechanisms of desensitization such as oral tolerance or mediator depletion in a controlled fashion.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; 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

Topics: AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Antifungal Agents; Dapsone; Female; Home Care Services; Humans; Male; Patient Compliance; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Pneumocystis carinii pneumonia (PCP) is a leading cause of illness and death in AIDS patients, accounting for about one-third of AIDS deaths. It was rare until the 1980s, when only 50 percent of patients with PCP survived an episode of the disease. Increasingly, prophylactic treatment is being used to prevent the onset of the disease. The use of oral antibiotics is discussed, and guidelines for early diagnosis and effective treatment are included.

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

In France, where 70% of adults are latently infected by toxoplasma, from 20% to 40% of patients with AIDS developed toxoplasmic encephalitis until recently. The prophylactic use of drugs which are active against pneumocystis and toxoplasma has proven to be efficient. These drugs are trimethoprim-sulfamethoxazole or dapsone-pyrimethamine. With the extent of these primary prophylaxis, there is a decrease of risk of toxoplasma encephalitis; thus the rate of toxoplasma encephalitis among opportunistic infections has fallen off from 19% of the patients in 1988 to 6% in 1994, in the department of infectious diseases of the Pitié-Salpêtrière hospital. However, toxoplasmic abscesses occurring despite the prophylaxis are frequently slow growing lesions which can become huge with a moderate mass effect, mimicking the pattern of primary cerebral lymphoma. The rule of antitoxoplasmic trial treatment must be strictly followed, even under prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Brain Abscess; Brain Neoplasms; Chemoprevention; Dapsone; Diagnosis, Differential; Drug Combinations; Encephalitis; France; Humans; Lymphoma, AIDS-Related; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

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: Acidosis, Renal Tubular; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Humans; Male; Middle Aged; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined.. In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men.. There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007).. Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

Topics: AIDS-Related Opportunistic Infections; Case-Control Studies; CD4 Lymphocyte Count; Female; HIV Seronegativity; HIV Seropositivity; Humans; Male; Pneumonia, Bacterial; Prospective Studies; Risk Factors; Smoking; Substance Abuse, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

Current dosage regimens of trimethoprim-sulfamethoxazole used to treat Pneumocystis carinii pneumonia in AIDS patients have been based on data from healthy subjects or patients without AIDS. The clearance and absorption characteristics of the drugs may potentially be different between patients with and without AIDS. This study was conducted to assess the pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients treated for P. carinii pneumonia. Patients received trimethoprim at 15 mg/kg of body weight and sulfamethoxazole at 75 mg/kg of body weight daily intravenously in three to four divided doses and were switched to the oral route when the regimen was tolerated. Serum samples for determination of drug concentrations were obtained over 12 h after intravenous and oral dosing. The pharmacokinetics of trimethoprim and sulfamethoxazole were compared in eight critically ill versus nine non-critically ill male patients and were as follows, respectively: clearance, 1.88 +/- 0.44 versus 1.73 +/- 0.64 ml/min/kg for trimethoprim and 0.40 +/- 0.12 versus 0.34 +/- 0.11 ml/min/kg for sulfamethoxazole; volume of distribution, 1.6 +/- 0.5 versus 1.5 +/- 0.5 liters/kg for trimethoprim and 0.5 +/- 0.3 versus 0.4 +/- 0.1 liters/kg for sulfamethoxazole; and half-life, 10.9 +/- 7.4 versus 11.3 +/- 4.0 h for trimethoprim, and 15.5 +/- 9.5 versus 14.3 +/- 4.7 h for sulfamethoxazole. No significant differences (P > 0.05) were observed between patient groups, although there was wide intersubject variability. Absorption appeared to be similar between the critically ill and non-critically patients: bioavailability was 97.5% +/- 22.4% versus 101.8% +/- 22.7% for trimethoprim and 86.2% +/- 17.9% versus 99.1% +/- 20.5% for sulfamethoxazole, respectively. Because of the similar pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients, the two groups of patients may receive similar dosages. Dosage adjustment does not appear to be required when switching from the intravenous to the oral route.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; APACHE; Biological Availability; Critical Illness; Half-Life; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia.. Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole and 128 others with pentamidine.. Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis (1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli was poor. Of the 41 diabetic patients, 26 required insulin therapy; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insulin antibodies, and insulitis were not detected. The pentamidine-treated dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pentamidine aerosols.. Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.

Topics: Adult; AIDS-Related Opportunistic Infections; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemia; Infusions, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Radioimmunoassay; Retrospective Studies; Risk Factors; 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

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

Topics: Acinetobacter; Acinetobacter Infections; Adult; AIDS-Related Opportunistic Infections; Community-Acquired Infections; Humans; Male; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; AIDS-Related Opportunistic Infections; Fatal Outcome; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Animals; Cohort Studies; Feces; Humans; Microsporida; Microsporidiosis; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Clotrimazole; Dapsone; Fluconazole; Humans; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Child; HIV Infections; Humans; Immunoglobulins, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Animals; Coccidiosis; Diarrhea; Eucoccidiida; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the risk of developing tuberculosis or other AIDS-related diseases (ARD) in HIV-infected patients treated with corticosteroids as adjunctive therapy for Pneumocystis carinii pneumonia (PCP).. Retrospective study.. Infectious Disease Service of a 1000-bed university teaching hospital in Barcelona, Spain.. HIV-infected patients diagnosed with PCP from 1985 to 1992. Patients were classified into two groups: steroid (group A) and non-steroid (group B) adjunctive therapy. Baseline characteristics, antibiotherapy, dose and duration of steroidal treatment were analysed. Endpoints were either the development of tuberculosis or other ARD or death.. From the 129 patients included in this study 72 were in group A and 57 in group B. No differences between groups were observed in baseline characteristics or mean follow-up period (15 versus 14 months, respectively). The mean total dose of steroids was 420 mg (range, 160-1260 mg) methylprednisolone or its equivalent in dexamethasone, with a mean treatment duration of 12 days (range, 4-33 days). No differences were found in the occurrence of tuberculosis or other endpoints in the first 6 months of follow-up. In addition, the cumulative rate of developing tuberculosis was 7% in group A and 12% in group B at 12 months of follow-up, and 13 versus 12% at 24 months (P = 0.622, Mantel-Cox): 4 versus 4% at 12 months and 27 versus 24% at 24 months (P = 0.873) for non-tuberculosis mycobacterial infection, and 40 versus 42% at 12 months, and 88 versus 66% at 24 months (P = 0.330) for non-mycobacterial ARD. The cumulative survival rate was 79 versus 71% and 46 versus 34% at 12 and 24 months, respectively (P = 0.526).. Our data suggest that the use of corticosteroids during PCP in HIV-infected patients at the doses and for the duration used in our patients did not enhance the risk of developing or relapsing tuberculosis or other ARD.

Topics: Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

We report two cases of prolonged fever in deeply immunocompromised patients with AIDS who had been receiving trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis for several months. Investigations of the cause of fever yielded normal or negative findings except that the polymerase chain reaction (PCR) for Toxoplasma gondii in the blood was positive in both cases, and PCR of the bronchoalveolar lavage fluid was positive in one case. After a few days of treatment with pyrimethamine plus clindamycin, the two patients became afebrile and the T. gondii PCR became negative. The patients probably had disseminated toxoplasmosis attenuated by TMP-SMZ. PCR examination of blood for evidence of T. gondii genome may be useful in screening for causes of unexplained fever in patients with AIDS, even those who receive prophylaxis with TMP-SMZ.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Fever; HIV-1; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Time Factors; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Infant, Newborn; Lung Diseases, Parasitic; Male; Respiratory Distress Syndrome, Newborn; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine factors associated with isosporiasis in persons with acquired immunodeficiency syndrome (AIDS) in Los Angeles County, data from the AIDS surveillance registry were analyzed for the eight-year period 1985-1992. Isosporiasis was reported in 127 (1.0%) of 16,351 persons with AIDS during the study period. Prevalence of infection was highest among foreign-born patients (3.2%), especially those from El Salvador (7.4%) and Mexico (5.4%), and in all persons of Hispanic ethnicity (2.9%). Persons with a history of Pneumocystis carinii pneumonia (PCP) were less likely than PCP-negative patients to have isosporiasis (0.2% and 1.4%, respectively, P < 0.01). A decrease in the prevalence of isosporiasis in patients negative for PCP was observed beginning in 1989 (P = 0.02). Prevalence decreased with age (P < 0.01, by chi-square test for trend). After controlling for multiple factors by logistic regression, isosporiasis was more likely to occur in foreign-born patients than in those born in the United States (adjusted odds ratio [OR] = 5.8, 95% confidence interval [CI] 3.4, 9.9, P < 0.001) and in Hispanics than in whites (non-Hispanics) (adjusted OR = 3.5, 95% CI 1.7, 7.2, P < 0.001). A prior history of PCP continued to be negatively associated with isosporiasis (adjusted OR = 0.2, 95% CI 0.1, 0.3, P < 0.001). Age and time remained independently associated with infection. These data suggest that isosporiasis among persons with AIDS in Los Angeles County may be related to travel exposure and/or recent immigration and that the use of trimethoprim-sulfamethoxazole (TMP-SMX) for PCP may effectively prevent primary infection or expression of latent isosporiasis. Physicians should have an increased index of suspicion for Isospora in AIDS patients with diarrhea who have immigrated from or traveled to Latin America, among Hispanics born in the United States, in young adults, and in those not receiving PCP prophylaxis. Food and water precautions should be advised and TMP-SMX prophylaxis considered for the prevention of Isospora infection for patients with human immunodeficiency virus infection who travel to Latin America and other developing countries.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Animals; Antimalarials; Coccidiosis; Ethnicity; Female; Humans; Isospora; Los Angeles; Male; Middle Aged; Odds Ratio; Population Surveillance; Prevalence; Registries; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anemia, Megaloblastic; Antifungal Agents; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

We describe patients with and without AIDS who had Cyclospora cayetanensis infection; these patients were seen at a tertiary care teaching hospital in Mexico City because of diarrheal disease. C. cayetanensis was detected by examination of fresh fecal preparations and acid-fast staining of fecal smears; the presence of other bacteria and parasites was excluded by standard methods. Fecal specimens from 12 patients contained C. cayetanensis. The overall mean duration of illness was 94 days. Seven of the 12 patients had AIDS; these patients presented with more weight loss than did patients without AIDS (P = .04). The patients with AIDS also tended to have a more prolonged illness. Two patients with AIDS had biliary disease that resolved when they received therapy with trimethoprim-sulfamethoxazole for cyclospora infection; the excretion of oocysts also ceased. Our data confirm that C. cayetanensis causes diarrhea in humans and a significant weight loss in patients with AIDS. In addition, Cyclospora could be involved in biliary disease in patients with AIDS.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Animals; Biliary Tract Diseases; Coccidiosis; Diarrhea; Eucoccidiida; Feces; Female; Humans; Male; Mexico; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography; Weight Loss

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Microbial Sensitivity Tests; Naphthalenes; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Lung; Lung Diseases; Male; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Encephalitis; Female; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Sulfonamides; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Cost-Benefit Analysis; Pneumocystis; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Methylprednisolone; Pneumonia, Pneumocystis; Pneumonia, Viral; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

As more drugs are approved for the prevention of opportunistic infections, concerns regarding the benefits and potential risks of these therapies are arising. A synopsis of the data for prophylaxis against opportunistic infections is provided for the following: Pneumocystis carinii pneumonia, fungal infections, Mycobacterium avium complex, cytomegalovirus infections, and toxoplasmosis. General precautions in using preventive medications for people with fewer than 100 CD4 plus cells are highlighted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Clinical Trials as Topic; Clotrimazole; Cytomegalovirus Infections; Dapsone; Fluconazole; Ganciclovir; Humans; Itraconazole; Leucovorin; Mycobacterium avium-intracellulare Infection; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Valacyclovir; Valine

Dr. Bernard Bihari, an AIDS specialist practicing in New York City, and other members of the Community Programs for Clinical Research on AIDS (CPCRA), have determined that some of the Public Health Services's recommendations for preventing opportunistic infections do not match the standards of care that the CPCRA developed nearly five years ago. The basic treatments provided by Bihari include using 1) TMP-SMZ and fluconazole to prevent, respectively, Pneumocystis carinii pneumonia (PCP) and cryptococcal meningitis in patients with CD4 counts below 200; 2) using high-dose acyclovir to prevent cytomegalovirus disease when the CD4 counts drop below 150; and 3) using clarithromycin and ethambutol to prevent Mycobacterium avium complex when CD4 counts drop below 100. This protocol has kept many patients from developing these opportunistic infections. Bihari notes that while the Centers for Disease Control and Prevention (CDC) recommendations are based on FDA-approved treatments and large clinical trials, private practitioners do not necessarily have to follow them.

Topics: AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Clarithromycin; Cytomegalovirus Infections; Ethambutol; Humans; Meningitis, Cryptococcal; Mycobacterium avium-intracellulare Infection; New York City; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A case history is presented of an HIV-infected female patient with a recurrence of Pneumocystis carinii pneumonia (PCP) and contraindications to use of most drugs for PCP, including pentamidine, trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, primaquine, and dapsone. Treatment alternatives discussed address risk-benefit analyses of using different drugs. The final treatment decision was to use escalating doses of TMP-SMX, since her previous adverse effects (fever and rash) are not an absolute contraindication to readministration of the drug. Results of this TMP-SMX were good with trivial side effects.

Topics: AIDS-Related Opportunistic Infections; Female; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

The fungus Pneumocystis carinii, which rarely if ever causes illness in otherwise healthy people, can cause potentially fatal pneumonia in patients with defects of cell-mediated immunity resulting, for example, from chemotherapy or immunosuppression after organ transplantation. P. carinii pneumonia also occurs in up to 85% of patients with acquired immunodeficiency syndrome (AIDS), in many of whom it is the first manifestation of the disease. This article discusses the prevention and treatment of P. carinii pneumonia in adults infected with the human immunodeficiency virus (HIV).

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Therapy, Combination; Fees, Pharmaceutical; Humans; Pentamidine; Pneumonia, Pneumocystis; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Drug Resistance, Microbial; Homosexuality, Male; Humans; Liver Diseases; Male; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Splenic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

An agar dilution method against trimethoprim, sulfamethoxazole, sulfisoxazole, and trimethoprim-sulfamethoxazole was used to test clinical isolates of Mycobacterium intracellulare (MI) and M. avium (MA) from both HIV-infected and non-infected patients. MI and MA isolates demonstrated similar susceptibility data and were inhibited by concentrations of sulfamethoxazole achievable in serum.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Drug Resistance, Microbial; Folic Acid Antagonists; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Sulfamethoxazole; Sulfanilamides; Sulfisoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Humans; Injections, Intravenous; Male; Middle Aged; Recurrence; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; 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

Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP). This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens. Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP. Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining. There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients. The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP. One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL. We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts. These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Dapsone; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with the acquired immunodeficiency syndrome are predisposed to cutaneous drug reactions. The reasons are poorly understood and the circumstances in which such patients can be treated through hypersensitivity are a matter of discussion. We assessed the value of clinical and laboratory parameters for predicting trimethoprim-sulfamethoxazole-induced skin reactions and the effects of continued trimethoprim-sulfamethoxazole therapy in such patients. We retrospectively studied all episodes of nonhypoxemic Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome who were treated with trimethoprim-sulfamethoxazole.. No clinical or laboratory parameters were found to be predictive of trimethoprim-sulfamethoxazole-induced cutaneous reactions. Of 38 patients treated with trimethoprim-sulfamethoxazole, 18 (47%) developed cutaneous reactions; these occurred within a median of 11 days (range, 7 to 20 days). Of these 18 patients, 12 (67%) continued to be treated with trimethoprim-sulfamethoxazole through hypersensitivity. Trimethoprim-sulfamethoxazole treatment was continued in 19 (95%) of the 20 patients who did not develop cutaneous reactions (P = .067). The mean duration of trimethoprim-sulfamethoxazole therapy was shorter (18 days) in patients who developed skin reactions than in those who did not (20 days) (P = .016). Noncutaneous side effects accounted for all but one interruption of therapy.. No clinical or laboratory parameters were found to be predictive of cutaneous reactions. By treating through hypersensitivity, 67% of our patients, who otherwise might have had to stop taking trimethoprim-sulfamethoxazole, were able to continue this essential drug therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Bacterial pneumonia is a very common cause of morbidity and mortality among persons with human immunodeficiency virus; however, the microbiologic characteristics (including antibiotic resistance) of bacterial pathogens causing community-acquired pneumonia in this population have not been well characterized or correlated with potentially predictive clinical presentation characteristics.. We conducted a retrospective cohort study of all adults known to have or to be at high risk for human immunodeficiency virus infection and hospitalized at San Francisco (Calif) General Hospital from May 1990 through April 1991, with a hospital discharge diagnosis of community-acquired bacterial pneumonia and for whom a medical records review confirmed that this diagnosis met a uniform case definition.. Two hundred sixteen eligible patients had one or more hospital admissions meeting the case definition. One or more etiologic pathogens were definitively identified in 75% of cases, with Streptococcus pneumoniae, Haemophilus species, Staphylococcus aureus, and gram-negative bacilli most frequently identified. In patients who had a bacteriologic diagnosis made, 18.6%, 6.8%, and 4.3% had pneumonia caused by pathogens resistant to ampicillin sodium, cefuroxime sodium, or trimethoprim-sulfamethoxazole, respectively. One hundred percent of pathogens isolated were susceptible to ceftazidime. Anemia and use of antibacterial medication at the time of hospital admission were the only independent predictors of ampicillin and cefuroxime resistance.. Nearly one fifth of human immunodeficiency virus-associated community-acquired bacterial pneumonias requiring hospitalization were caused by ampicillin-resistant pathogens, and presenting clinical characteristics did not consistently define a subset of patients at lower risk for resistance. In the absence of a diagnostic sputum Gram's stain and pending definitive microbiologic diagnosis, initial empiric therapy should be with a second- or third-generation cephalosporin or possibly trimethoprim-sulfamethoxazole.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Ampicillin Resistance; Bacteria; Cefuroxime; Community-Acquired Infections; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Regression Analysis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (T/S) is an effective and important prophylactic medication for HIV-infected patients that must frequently be discontinued because of allergic reactions.. Our objective was to assess the safety, the frequency of success, and the duration of desensitization to T/S in HIV-infected patients.. We studied oral desensitization with T/S of patients with a history of allergy to the medication and longitudinal follow-up. Twenty-eight men with a history of T/S-induced skin rashes were studied. Mean age was 35 years (range, 26 to 50 years). Mean CD4 count was 89 cells/mm3 (range, 0/mm3 to 210/mm3). Patients were seen every 4 to 6 weeks. Mean follow-up was 19.07 weeks (range 2 to 81 weeks).. After 32 weeks, 23 of 28 (82%) patients were successfully desensitized (four had rashes develop, and one could not continue for personal reasons). Of the 23 patients who were successfully desensitized, six were known to have subsequently discontinued T/S (four had rashes; two discontinued on the advice of their personal primary physicians). Six patients were lost to follow-up. One patient died of pulmonary Kaposi's sarcoma. Ten patients are taking the medication regularly without any problems.. T/S desensitization is a simple, safe and effective means to provide it for most patients with a history of "allergic" rashes.

Topics: Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival.. Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease.. First episode of TE occurred in 75 out of 499 patients participating in the trial.. Kaplan-Meier estimates and semi-parametric Cox's model were used.. A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8).. The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Encephalitis; Female; Humans; Male; Middle Aged; Pyrimethamine; Sulfadiazine; Sulfadoxine; Survival Rate; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Cryptosporidiosis; Drug Therapy, Combination; Humans; Male; Middle Aged; Respiratory Tract Infections; Spiramycin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Injections, Intramuscular; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Pneumococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia is frequent in patients with cellular immunity impairments, specially those with AIDS. We communicate our experience in 20 patients (15 with AIDS) with Pneumocystis carinii pneumonia confirmed by the finding of trophozoites or cysts. Clinical manifestations were cough in 75% of cases, dyspnea in 70% and fever in 65%. Eighty five percent of cases had diffuse reticular and nodular radiological densities. Nineteen patients had an increased alveolar-arterial O2 gradient. Nineteen patients were treated with trimethropim-sulphamethoxazole (TMP-SMX) and 4 with pentamidine isethionate (1 due to previous allergy and 3 due to poor response to TMP-SMX). Three patients died during the acute episode. Of the survivors, 13 died within 2 to 44 months later (14.5 +/- 12 months). It is concluded that AIDS is the most frequent underlying condition in patients with Pneumocysts carinii pneumonia and that long term survival is low.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; Humans; Immunocompromised Host; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of probable pentamidine-induced acute pancreatitis.. A patient was hospitalized because of fever, dyspnea, and productive cough. Chest X-ray revealed diffuse alveolar infiltrates, and the examination of bronchoalveolar lavage demonstrated the presence of Pneumocystis carinii. Intravenous cotrimoxazole was administered but the patient's condition did not improve. As secondary leukopenia appeared, the treatment was changed to pentamidine isethionate 4 mg/kg/d i.v. On day 5 of this new therapy, the patient experienced abdominal pain, and both blood and urine amylase concentrations raised to 330 U/L and 3960 U/L, respectively. The patient died 48 hours later, and signs of acute pancreatitis were observed in necropsy.. With reference to a classical method for estimating the probability of adverse drug reactions, a probable relationship between pentamidine therapy and acute pancreatitis was found in this patient. Furthermore, no alternative causes of pancreatitis were present.. It is likely that pentamidine administration in our patient resulted in an acute episode of pancreatitis. Serum and urine amylase concentrations should be monitored in patients receiving this drug.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Methylprednisolone; Pancreatitis; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia has been the most common life-threatening opportunistic infection in patients with acquired immunodeficiency syndrome. With a better understanding of the natural history of HIV infection, however, we have come to realize that prophylaxis against P carinii can prevent the majority of such pneumonias. In this article, I focus on the rationale behind such prophylaxis, as well as the choices and dilemmas the clinician faces in deciding on the most appropriate therapy and when it should be instituted.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Clindamycin; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Primaquine; Pyrimethamine; Streptococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Listeria monocytogenes; Listeriosis; Male; Sulfamethoxazole; Thymidine Monophosphate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Male; Mycobacterium avium-intracellulare Infection; Nursing Assessment; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS).. We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men.. A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three six-month periods before the diagnosis of AIDS (0 to 6, > 6 to 12, and > 12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not.. M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Candidiasis; CD4-Positive T-Lymphocytes; Cohort Studies; Cytomegalovirus Infections; Dapsone; Esophageal Diseases; HIV-1; Humans; Leukocyte Count; Male; Mycobacterium avium-intracellulare Infection; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: AIDS-Related Opportunistic Infections; Humans; Male; Meningitis, Bacterial; Middle Aged; Nocardia asteroides; Nocardia Infections; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination

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

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Bacterial Infections; Cohort Studies; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

An unusual acute hypotensive syndrome has been observed in association with administration of trimethoprim-sulfamethoxazole (TMP-SMZ) to patients with human immunodeficiency virus (HIV) infection. In the 11 cases that have been reported, the syndrome differs from classic anaphylaxis and resembles septic shock. Mediation by tumor necrosis factor (TNF) has been hypothesized, but the mechanism has not been characterized with cytokine assays, and no invasive hemodynamic measurements have been reported. We describe a case of recurrent hyperdynamic shock--without classic features of anaphylaxis, without detectable IgE antibodies against TMP or SMZ, and without detectable levels of TNF--involving an HIV-infected patient rechallenged with TMP-SMZ.

Topics: Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Complement System Proteins; Fever; Hemodynamics; Humans; Hypotension; Interleukin-6; Male; Pneumonia, Pneumocystis; Shock; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Choroiditis; Eye Infections, Fungal; Humans; Male; Pentamidine; Pneumocystis Infections; Premedication; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration.. Retrospective cohort study.. An urban teaching hospital.. Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded.. Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization.. High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Cohort Studies; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.

Topics: AIDS-Related Opportunistic Infections; Biopsy; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoscopy; Decision Support Techniques; Decision Trees; HIV Seropositivity; Humans; Lung Diseases; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Prevalence; Probability; Quality of Life; Sensitivity and Specificity; Survival Rate; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Angiography; Choroiditis; Humans; Male; Pneumocystis Infections; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A newly synthesized biguanide inhibitor of dihydrofolate reductase in Plasmodium species was evaluated for its anti-Pneumocystis carinii activity. The compound N-3-(2,4,5-trichlorophenoxypropyloxy)-N'-(1-methylethyl)imidoca rbonimidic diamide hydrochloride, designated PS-15, was administered prophylactically and therapeutically to immunosuppressed rats latently infected with P. carinii. Doses of 5 and 25 mg of PS-15 per kg of body weight per day given orally during 7 weeks of dexamethasone immunosuppression prevented P. carinii infection in all (100%) 19 rats given the drug, while 6 of 9 (67%) untreated control rats developed P. carinii pneumonitis. A single weekly dose of 50 mg of PS-15 per kg also prevented the infection in all 10 rats. P. carinii pneumonitis was established after 4 weeks of immunosuppression and was then treated orally for 3 weeks with 25, 5, and 1 mg of PS-15 per kg/day. Complete resolution of the infection occurred in all (100%) 10 rats given 25 mg of PS-15, 6 of 9 (67%) rats given 5 mg of PS-15, and 6 of 8 (75%) rats given 1.0 mg of PS-15 per kg per day and in all (100%) 9 rats treated with trimethoprim-sulfamethoxazole. PS-15 was well tolerated at all doses. Because drug studies in the P. carinii rat model have been highly predictable of the effects of drugs on the disease in humans, these experiments suggest that PS-15 may have promise as a drug for the treatment of P. carinii pneumonitis in humans.

Topics: AIDS-Related Opportunistic Infections; Animals; Antimalarials; Dose-Response Relationship, Drug; Folic Acid Antagonists; Imides; Immunosuppressive Agents; Lung; Male; Phenyl Ethers; Pneumocystis Infections; Pneumonia, Pneumocystis; Proguanil; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

A group of clinical, immunologic, and virologic variables was examined to determine if any predicted the development of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMZ) during treatment of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus (HIV) infection. Hypersensitivity occurred in 39 (27%) of 143 patients, who had significantly higher total lymphocyte and CD4+ and CD8+ cell counts and CD4:CD8 ratios than did those who did not develop hypersensitivity. Regression analysis identified having a CD4:CD8 ratio > 0.10 (95% confidence interval [CI], 1.75-3.94; P = .02) and treatment for < 14 days (95% CI, 1.57-3.75; P = .04) as independently predictive of hypersensitivity. Use of corticosteroids tended to reduce the frequency of hypersensitivity (7% vs. 30%; P = .07). T lymphocytes may be important in the pathogenesis of these hypersensitivity reactions. As the frequency of hypersensitivity declines with disease progression, T lymphocytes could be effector cells in these reactions or their sensitivity to TMP-SMZ may decline with HIV disease progression.

Topics: Adrenal Cortex Hormones; Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Viral; CD4-CD8 Ratio; Cytomegalovirus Infections; Drug Hypersensitivity; Humans; Immunoglobulins; Male; Middle Aged; Pneumonia, Pneumocystis; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Inhalation; Aerosols; AIDS-Related Opportunistic Infections; Child, Preschool; Dapsone; Drug Administration Schedule; Humans; Injections, Intravenous; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Time Factors; Treatment Failure; 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: 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

Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV-positive patients are not yet clearly established.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Follow-Up Studies; Humans; Klebsiella; Male; Oropharynx; Rhinoscleroma; Trimethoprim, Sulfamethoxazole Drug Combination

Atypical pulmonary manifestations of Pneumocystis carinii infection and fair numbers of extrapulmonary and disseminated infections have lately been documented in patients with human immunodeficiency virus infection treated prophylactically with inhalative pentamidine. We report the case of a 32-year-old homosexual patient who was assessed for complaints of night sweats, weight loss, and progressive malaise. The patient denied any respiratory tract symptoms such as cough, sputum production, pleuritic chest pain, or shortness of breath. Chest X-ray revealed two large round noncavitating lesions in the lower lobe of the right lung. Pneumocystomas were diagnosed by fine-needle aspiration. A 3-week course of intravenous high-dose cotrimoxazole resulted in amelioration of symptoms but no change in the radiographic appearance of the pulmonary lesions. Four months later the patient is alive and stable and is being treated with pentamidine inhalation of 300 mg per 2 weeks and two tablets of pyrimethamine sulfadoxine per week.

Topics: Administration, Inhalation; Adult; AIDS-Related Opportunistic Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Humans; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine.

Topics: Administration, Intranasal; Adult; Aerosols; AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Dapsone; Female; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Predictive Value of Tests; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Fluconazole; Humans; Incidence; Lung Diseases, Fungal; Male; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Angiomatosis, Bacillary; Anti-Bacterial Agents; Blood; Gram-Negative Bacteria; Humans; Male; Rickettsia; Rickettsia Infections; Trimethoprim, Sulfamethoxazole Drug Combination

To study the incidence, clinical features, treatment and outcome of patients with Salmonella, Shigella or Campylobacter infection.. Retrospective analysis.. Two dedicated HIV units within a London teaching hospital.. All patients with Salmonella, Shigella or Campylobacter infection were reviewed retrospectively by correlating the records of the gastrointestinal and microbiology departments with the computerized records of all HIV-positive patients attending the two clinics.. Between July 1985 and June 1991, 56 episodes of Salmonella, 37 of Campylobacter and eight of Shigella infection were documented in HIV-seropositive patients. Shigella was most likely to occur early in HIV disease, whilst patients with Campylobacter or Salmonella were more likely to have had a previous AIDS diagnosis. Septicaemica was most common in patients with Salmonella and was especially likely to occur in individuals with an AIDS diagnosis. Relapse of infection was common in patients with Salmonella, especially in those with low CD4 lymphocyte counts, those with an initial septicaemic illness and those not treated with ciprofloxacin.. Patients with Salmonella who have low CD4 lymphocytes counts and/or a septicaemic illness should be considered for life-long secondary prophylaxis with ciprofloxacin because of the high rate of relapse observed. Administration of zidovudine or cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia may prevent the development of salmonellosis: significantly fewer patients with this infection were taking these drugs than patients with Campylobacter.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Campylobacter Infections; CD4-Positive T-Lymphocytes; Ciprofloxacin; Dysentery, Bacillary; Feces; HIV Seropositivity; Humans; Leukocyte Count; Male; Middle Aged; Pneumonia, Pneumocystis; Recurrence; Retrospective Studies; Salmonella Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Tuberculosis is a common cause of cavitating pneumonia in Singapore. In patients with the human immunodeficiency virus (HIV), cavitary pneumonias mimicking tuberculosis can mislead the clinician, delaying diagnosis, resulting in increased morbidity. We describe a HIV seropositive patient with cavitating pneumonia in whom the diagnosis of Pneumocystis carinii pneumonia (PCP) was ultimately established only on bronchoscopy.. In February 1991, a 30-year old single, Chinese male, who had not has sexual intercourse with another man but did have it with a woman while in another country 12 months earlier, sought medical care at Tan Tock Seng Hospital in Singapore. He had a productive cough for 3 months, lost 5 kg over 4 months, and had been gasping for breath for 3 days. Upon admission, he had a low grade fever and breathed very rapidly while resting. The apical segment of the right lower lobe of the lung had a 3 x 2 cm cavity which was filling with exudate. A sputum smear did not indicate acid fast bacilli in 2 of 3 samples and blood cultures did not yield aerobic or anaerobic bacteria. The Western blot test revealed HIV antibodies. The absolute CD4 lymphocyte count stood at 80/cu mm compared with more than 500/cm mm in healthy individuals. Physicians used a bronchoscope to do bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB), both of which disclosed cysts of Pneumocystis carinii. Treatment first consisted of trimethoprim/sulfamethoxazole for 7 days and antituberculosis chemotherapy for 2 weeks until the physicians realized he had Pneumocystis carinii. They switched the treatment to iv pentamidine isethionate because he still had a fever after 7 days. This treatment was successful. Physicians then administered Zidovudine (AZT) and aerosolized pentamidine each month. As of mid-1992 he was still healthy. In addition to the BAL/TBLB results indicating Pneumocystis carinii and excluding tuberculosis, other features excluding tuberculosis were a Mantoux reading of O, absence of hilar and/or mediastinal lymphadenopathy, response to pentamidine isethionate, and sputum and blood cultures that did not indicate Mycobacterium species.

Topics: Adult; AIDS-Related Opportunistic Infections; Biopsy; Diagnosis, Differential; Humans; Lung; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Zidovudine

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

Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine.. A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome-related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival.. Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim-sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim-sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP.. Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease.

Topics: Acquired Immunodeficiency Syndrome; Actuarial Analysis; AIDS-Related Opportunistic Infections; Case-Control Studies; Cohort Studies; Female; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Proportional Hazards Models; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

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

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

Topics: AIDS-Related Opportunistic Infections; Child; HIV-1; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination