abacavir and AIDS-Related-Opportunistic-Infections

Topics: Acquired Immunodeficiency Syndrome; Adenine; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Darunavir; Decompressive Craniectomy; Dideoxynucleosides; Female; Humans; Intracranial Hypertension; Lopinavir; Medication Adherence; Meningoencephalitis; Organophosphonates; Sulfonamides; Tenofovir; Treatment Outcome

Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Dideoxynucleosides; Drug Hypersensitivity; Genetic Predisposition to Disease; HIV Protease Inhibitors; Humans; Reverse Transcriptase Inhibitors

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

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

The prevalence of vitamin D insufficiency in Africans with AIDS-associated Kaposi sarcoma (AIDS-KS) and the role of vitamin D in AIDS-KS progression are unknown. We hypothesized that a high prevalence of vitamin D deficiency would be found in Zimbabweans with AIDS-KS and that low baseline vitamin D would correlate with progression of AIDS-KS.. Ninety subjects were enrolled in a prospective pilot study investigation of the effect of antiretroviral therapy in the treatment of AIDS-KS in Harare, Zimbabwe. Co-formulated abacavir, lamivudine, and zidovudine was initiated; chemotherapy was provided at the discretion of the provider. Participants were followed for 96 weeks. 25-Hydroxyvitamin D was measured in stored specimens collected at study entry. The relationship between vitamin D and clinical response was described by odds ratio and 95% confidence interval.. Samples were available for 85 participants; 45 (53%) subjects had inadequate (<75 nmol/l) 25-hydroxyvitamin D. HIV-1 RNA was significantly higher among those with insufficient vitamin D (4.7 vs. 4.5 log, p = 0.04). Tumor response, survival, and KS-IRIS were not associated with vitamin D (p ≥ 0.3).. Vitamin D insufficiency was common among Zimbabweans with AIDS-KS but not associated with outcomes after initiation of antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Dideoxynucleosides; Disease Progression; Female; Herpesvirus 8, Human; HIV-1; Humans; Lamivudine; Male; Middle Aged; Odds Ratio; Pilot Projects; Prospective Studies; RNA, Viral; Sarcoma, Kaposi; Survival Analysis; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Zidovudine; Zimbabwe

A 26-year-old male living with human immunodeficiency virus (HIV) and who had previously been treated for ocular syphilis presented to the Emergency Department with progressive vision loss and uveitis. The efficacy of standard management for neurosyphilis in HIV and recurrence was examined.

Topics: Adult; AIDS-Related Opportunistic Infections; Dideoxynucleosides; Eye Infections, Bacterial; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Lamivudine; Male; Neurosyphilis; Oxazines; Penicillin G; Piperazines; Pyridones; Syphilis; Syphilis Serodiagnosis; Treatment Outcome; Treponema pallidum; Uveitis; Visual Acuity

Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year-old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/μL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have poor drug concentration within CSF could be considered at risk for opportunistic infection of the brain. Further larger investigation needs to confirm this finding.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Darunavir; Dideoxynucleosides; Drug Substitution; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Rilpivirine; Ritonavir; Virus Replication

Topics: Abscess; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Axilla; Clarithromycin; Darunavir; Dideoxynucleosides; Enfuvirtide; Ethambutol; HIV Envelope Protein gp41; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Isoniazid; Lamivudine; Lymph Node Excision; Lymphadenitis; Male; Mycobacterium avium-intracellulare Infection; Peptide Fragments; Pyrazinamide; Rifampin; Ritonavir; Streptomycin; Sulfonamides

Adverse effects of combination antiretroviral therapy (CART) commonly result in treatment modification and poor adherence.. We investigated predictors of toxicity-related treatment modification during the first year of CART in 1318 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from the Swiss HIV Cohort Study who began treatment between January 1, 2005, and June 30, 2008.. The total rate of treatment modification was 41.5 (95% confidence interval [CI], 37.6-45.8) per 100 person-years. Of these, switches or discontinuations because of drug toxicity occurred at a rate of 22.4 (95% CI, 19.5-25.6) per 100 person-years. The most frequent toxic effects were gastrointestinal tract intolerance (28.9%), hypersensitivity (18.3%), central nervous system adverse events (17.3%), and hepatic events (11.5%). In the multivariate analysis, combined zidovudine and lamivudine (hazard ratio [HR], 2.71 [95% CI, 1.95-3.83]; P < .001), nevirapine (1.95 [1.01-3.81]; P = .050), comedication for an opportunistic infection (2.24 [1.19-4.21]; P = .01), advanced age (1.21 [1.03-1.40] per 10-year increase; P = .02), female sex (1.68 [1.14-2.48]; P = .009), nonwhite ethnicity (1.71 [1.18-2.47]; P = .005), higher baseline CD4 cell count (1.19 [1.10-1.28] per 100/microL increase; P < .001), and HIV-RNA of more than 5.0 log(10) copies/mL (1.47 [1.10-1.97]; P = .009) were associated with higher rates of treatment modification. Almost 90% of individuals with treatment-limiting toxic effects were switched to a new regimen, and 85% achieved virologic suppression to less than 50 copies/mL at 12 months compared with 87% of those continuing CART (P = .56).. Drug toxicity remains a frequent reason for treatment modification; however, it does not affect treatment success. Close monitoring and management of adverse effects and drug-drug interactions are crucial for the durability of CART.

Topics: Adenine; Adult; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Deoxycytidine; Dideoxynucleosides; Drug Therapy, Combination; Emtricitabine; Female; HIV Infections; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Nevirapine; Oligopeptides; Organophosphonates; Proportional Hazards Models; Prospective Studies; Pyridines; Pyrimidinones; Risk Factors; Switzerland; Tenofovir; Zidovudine

Cryptococcus neoformans is an opportunistic pathogen that can manifest in immunocompromised patients with acquired immune deficiency syndrome. Prevention of cryptococcosis and other opportunistic diseases is an objective in the management of human immunodeficiency virus (HIV)-infected patients. The goal of highly active antiretroviral therapy (HAART) is to reduce the viral loads and enhance CD4 counts in HIV-infected patients. These 2 mechanisms keep HIV-infected patients healthier and enhance their immune systems, thus reducing and often preventing opportunistic infections such as ocular cryptococcal infections. Discontinuation of HAART can lead to ocular opportunistic infections such as cryptococcal choroiditis.. Presented here is a case of a patient who was treated successfully with HAART of stavudine (D4T), abacavir (Ziagen), ritonavir (Norvir), and saquinavir (Invirase). His last CD4 count before HAART was discontinued was 131 cells/mm(3), and viral load was less than 50 copies/mL. He discontinued his HAART regimen for 2 years and presented to the emergency room with complaints of a severe headache with neck pain, lightheadedness, nausea, disorientation, and unsteady gait. Lumbar puncture results showed cryptococcal infection, and the patient was admitted for the treatment of cryptococcal meningitis with amphotericin B and 5-flucytosine. Cryptococcal choroiditis was diagnosed after treatment of the meningitis. After resolution, his resultant visual acuities were 10/350 in the right eye and 10/600 in the left eye. He is on a maintenance dose of antifungal therapy and has been reinitiated on HAART of abacavir/zidovudine/lamivudine (Trizivir) and lopinavir/ritonavir (Kaletra).. This case exemplifies the importance of HAART in the prevention of opportunistic infections, cryptococcal meningitis/choroiditis in particular. Eye care professionals can play a role in encouraging patients to comply with their HAART regimens.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Choroiditis; Cryptococcus neoformans; Dideoxynucleosides; Eye Infections, Fungal; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Ritonavir; Saquinavir; Stavudine

Influenza is a major cause of morbidity for people with significant underlying disease, but the impact of influenza on people infected with human immunodeficiency virus (HIV) remains unclear. We studied a population of HIV-infected adults during the 1998-1999 influenza season to see whether influenza had any adverse effects on the course of HIV infection. During 5 months of follow-up, we found no unique clinical manifestations or negative impact on CD4(+) cell count, virus load, or clinical progression of HIV disease. Although half of our cohort received antibiotic therapy, none received specific anti-influenza therapy and none required hospitalization. Acute influenza does not appear to be a risk for progression of HIV disease.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Dideoxynucleosides; Disease Outbreaks; Disease Progression; Female; Humans; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Reverse Transcriptase Inhibitors

HIV/AIDS was the subject of some of the presentations at the annual meeting of the Infectious Diseases Society of America (ISDA). The most significant presentation was by Dr. Anthony Fauci, who described the possibility of using IL-2 to purge latently-infected CD4 cells. Other presentations covered treatment of primary HIV infection, updates on developments of nucleoside inhibitors, an efavirenz (EFV) update, PCP prophylaxis, care delivery options, and co-infection with tuberculosis.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Benzoxazines; Colorado; Cyclopropanes; Dideoxynucleosides; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Interleukin-2; Oxazines; Pneumonia, Pneumocystis; Practice Patterns, Physicians'; Reverse Transcriptase Inhibitors; Tuberculosis; United States

The 5th Conference on Retroviruses and Opportunistic Infections included 837 abstracts and oral presentations on clinical and basic science aspects of HIV. A major theme of the conference was the effectiveness of newer anti-HIV therapies, and there were many sessions dealing with combination treatments, including six-drug treatments. Results of studies with several drugs, including abacavir, efavirenz, amprenavir, PMPA Prodrug, adefovir dipivoxil, hydroxyurea, and protease inhibitors in several combinations are summarized. Treatments for opportunistic infections, including MAC, CMV retinitis, herpesvirus, and tuberculosis, are also presented.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antiviral Agents; Benzoxazines; Carbamates; Chicago; Clinical Trials as Topic; Congresses as Topic; Cyclopropanes; Dideoxynucleosides; Drug Hypersensitivity; Drug Interactions; Drug Therapy, Combination; Drugs, Investigational; Furans; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxyurea; Oxazines; Reverse Transcriptase Inhibitors; Sulfonamides

Ron Baker of the San Francisco AIDS Foundation discusses the presentation highlights at the Fifth Conference on Retroviruses and Opportunistic Infections with Dr. Harvey Bartnoff of the AIDS Virus Education and Research Institute, Dr. Steven Deeks of the University of California, and Dr. Stephan Follansbee of the Institute for HIV Research and Treatment. The panel discusses trends in testing and treatment, drug interactions, and studies of several therapies, including amprenavir, hydroxyurea, and adefovir. Dr. Mellors described study results of abacavir used in combination with protease inhibitors. The panel of doctors emphasize that abacavir is very effective; however, it needs to be used carefully in case a reaction occurs. If the drug is restarted, the allergic reaction may result in death.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Benzoxazines; Carbamates; Clinical Trials as Topic; Congresses as Topic; Cyclopropanes; Dideoxynucleosides; Drug Resistance, Microbial; Drug Therapy, Combination; Drugs, Investigational; Furans; Genetic Techniques; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxyurea; Oxazines; Reverse Transcriptase Inhibitors; Sulfonamides; Viral Load

The 12th World AIDS Conference in Geneva brought together AIDS researchers, medical care providers, advocates, and people living with HIV to discuss implications related to providing global access to care. New drugs have decreased deaths and opportunistic infections in developed countries, but developing countries are becoming overwhelmed by the number of new patients. The World Health Organization estimates that the majority of the 30.6 million people infected with HIV/AIDS worldwide will die within a decade unless a cure is found or treatments are made accessible to them. Researchers are no longer optimistic about the feasibility of viral eradication, and instead are looking for strategies to overcome the virus that continues to live in latent reservoirs in the body. Descriptions are given of several new drugs currently being studied, including abacavir, amprenavir, efavirenz, ABT 378, and Hydroxyurea. Progress is also highlighted about dosing regimens, antiretroviral resistance, and reconstitution of the immune system.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Benzoxazines; Carbamates; CD4-Positive T-Lymphocytes; Clinical Trials as Topic; Congresses as Topic; Cyclopropanes; Dideoxynucleosides; Drug Resistance, Microbial; Drug Therapy, Combination; Enzyme Inhibitors; Furans; Health Services Accessibility; HIV Protease Inhibitors; Humans; Hydroxyurea; Lopinavir; Oxazines; Patient Care Planning; Pyrimidinones; Remission Induction; Reverse Transcriptase Inhibitors; Sulfonamides; Switzerland; Virus Replication