abacavir and Hypersensitivity

Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

Topics: Adolescent; Africa; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Child; Child, Preschool; Dideoxynucleosides; Female; HIV Infections; Humans; Hypersensitivity; Incidence; Infant; Male

The HLA-B 5701 allele is predictive of hypersensitivity reaction to abacavir, a response herein termed "ABC-HSR." This study of 1,103 individuals infected with human immunodeficiency virus assessed the usefulness of genotyping a HCP5 single-nucleotide polymorphism (SNP), rs2395029, in relation to ABC-HSR. In populations with European ancestry, rs2395029 is in linkage disequilibrium with HLA-B 5701. The HCP5 SNP was present in all 98 HLA-B 5701-positive individuals and was absent in 999 of 1005 HLA-B 5701-negative individuals. rs2395029 was overrepresented in 25 individuals with clinically likely ABC-HSR, compared with its frequency in 175 ABC-tolerant individuals (80% vs. 2%, respectively; P < .0001). Therefore, HCP5 genotyping could serve as a simple screening tool for ABC-HSR, particularly in settings where sequence-based HLA typing is not available.

Topics: Anti-HIV Agents; Carrier State; Cohort Studies; Dideoxynucleosides; Genotype; HLA-B Antigens; Humans; Hypersensitivity; Major Histocompatibility Complex; Polymorphism, Single Nucleotide; Predictive Value of Tests; RNA, Long Noncoding; RNA, Untranslated

The association of human leukocyte antigen-B*5701 with abacavir hypersensitivity varies depending on ethnic origin. We confirmed the high specificity of B*5701 in the ethnically mixed French population and used a rapid and inexpensive polymerase chain reaction strategy to evaluate the predictiveness of B*5701 screening. The incidence of hypersensitivity decreased from 12% before screening to 0% after screening, and the rate of unwarranted interruptions of abacavir therapy decreased from 10.2% to 0.73%. We therefore recommend the implementation of this cost-effective screen before treatment with abacavir.

Topics: Anti-HIV Agents; Black People; Dideoxynucleosides; Female; France; Genetic Testing; HIV; HIV Infections; HLA-B Antigens; Humans; Hypersensitivity; Incidence; Male; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Suburban Population; Urban Population; White People

To analyze the safety and effectiveness of abacavir, lamivudine, and zidovudine (ABC/3TC/ZDV) in antiretroviral therapy (ART)-naive HIV-infected patients.. Retrospective observational cohort study.. We analyzed all consecutive ART-naive HIV-infected patients who initiated ABC/3TC/ZDV in 71 centers throughout Spain and had a clinical visit and laboratory data at least 16 weeks after initiating this regimen. We assessed safety, mortality, new AIDS-defining conditions (ADCs) and treatment failure, the latter defined by any of the following: (1) reduction in plasma HIV-1 viral load (pVL) <1 log during the first 12 weeks of ART, unless it was less than the lower limit of quantification (LOQ); (2) failure to achieve a pVL or = LOQ after achieving a pVL

Topics: Adult; Anti-HIV Agents; Cohort Studies; Dideoxynucleosides; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Hypersensitivity; Lamivudine; Male; Patient Compliance; Retrospective Studies; Spain; Treatment Failure; Zidovudine

The clinical treatment of patients with HIV and adverse drug events may be enhanced by an understanding of the underlying mechanisms. About 4% of patients with HIV receiving the potent antiretroviral drug abacavir develop a hypersensitivity reaction. This idiosyncratic reaction appears to have an immunologic component that has yet to be defined. Given that the T-cell type 2 cytokine IL-4 may be overproduced by patients with allergy or other immunologic dysregulation, an index cytokine profile could help elucidate the character of a drug-specific hypersensitivity reaction.. Quantitation of the production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma in patients with abacavir-related hypersensitivity.. Intracellular cytokines were enumerated in blood T cells by flow cytometry. Subjects were grouped for evaluation as patients with a hypersensitive response after abacavir treatment, patients initiating abacavir who also were evaluated again after 1 month on abacavir, patients on abacavir for 6 months without hypersensitivity, and HIV-naive control individuals.. There was a significant association between increased IL-4 production by CD4 and CD8 T lymphocytes and hypersensitivity reactions to abacavir. Lymphocytes from hypersensitive subjects expressed CD28 and the anti-HIV chemokine macrophage inflammatory protein 1beta with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional.. The expansion of type 0 and type 2 T cells phenotyped by IL-4 production may correlate with abacavir-associated hypersensitivity. The data suggest a cytokine bias that may facilitate B-cell differentiation and downregulate T-cell cytotoxic responses.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dideoxynucleosides; Drug Therapy, Combination; Flow Cytometry; HIV Infections; HIV-1; Humans; Hypersensitivity; Interferon-gamma; Interleukin-4; Leukocytes, Mononuclear; Lymphocyte Count

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Australia; Dideoxynucleosides; Ethnicity; Humans; Hypersensitivity; Immune System; Reverse Transcriptase Inhibitors