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

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-B5701 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-B5701 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.
Authors	Arlene R Hughes, Michael Mosteller, Aruna T Bansal, Kirstie Davies, Stephen A Haneline, Eric H Lai, Keith Nangle, Trevor Scott, William R Spreen, Liling L Warren, Allen D Roses, CNA30027 Study Team, CNA30032 Study Team
Journal	Pharmacogenomics (Pharmacogenomics) Vol. 5 Issue 2 Pg. 203-11 (Mar 2004) ISSN: 1462-2416 [Print] England
PMID	15016610 (Publication Type: Comparative Study, Journal Article, Multicenter Study)
Chemical References	Anti-HIV Agents Dideoxynucleosides Genetic Markers HLA-B Antigens Tumor Necrosis Factor-alpha abacavir
Topics	Anti-HIV Agents (adverse effects) Black People (genetics) Case-Control Studies Dideoxynucleosides (adverse effects) Drug Hypersensitivity (etiology, metabolism) Female Genetic Markers Genetic Variation Genotype HLA-B Antigens (genetics) Humans Male Polymorphism, Single Nucleotide Retrospective Studies Tumor Necrosis Factor-alpha (genetics) White People (genetics)

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