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      Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations.

      Pharmacogenetics
      African Continental Ancestry Group, genetics, Anti-HIV Agents, adverse effects, Case-Control Studies, Dideoxynucleosides, Drug Hypersensitivity, etiology, metabolism, European Continental Ancestry Group, Female, Genetic Markers, Genetic Variation, Genotype, HLA-B Antigens, Humans, Male, Polymorphism, Single Nucleotide, Retrospective Studies, Tumor Necrosis Factor-alpha

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          Abstract

          Abacavir is an effective antiretroviral drug used to treat HIV-1 infection. Approximately 5% of patients treated with abacavir develop a hypersensitivity reaction that requires discontinuation of the drug. In an initial pharmacogenetic study conducted in a predominantly White male population, multiple markers in the human leukocyte antigen (HLA)-B chromosomal region were associated with hypersensitivity to abacavir. The HLA-B*5701 association has now been confirmed in White males in a subsequent, larger study (n=293, p=4.7 x 10(-18)) and is also observed in White females (n=56, p=6.8 x 10(-6)) and Hispanics (n=104, p=2.1 x 10(-4)). HLA-B*5701 was not associated with hypersensitivity in Blacks (n=78, p=0.27). HLA-B*5701 alone lacks sufficient predictive value to identify patients at risk for hypersensitivity to abacavir across diverse patient populations. Efforts are ongoing to identify markers with sufficient sensitivity and specificity to be clinically useful. Even after a marker set is identified, appropriate clinical identification and management of hypersensitivity to abacavir must remain the cornerstone of clinical practice.

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