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

    Arlene R Hughes

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Michael Mosteller

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Aruna T Bansal

    GlaxoSmithKline, New Frontiers Science Park (North), Third Avenue, Harlow, Essex, CM19 5AW, UK

    ,
    Kirstie Davies

    GlaxoSmithKline, New Frontiers Science Park (North), Third Avenue, Harlow, Essex, CM19 5AW, UK

    ,
    Stephen A Haneline

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Eric H Lai

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Keith Nangle

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Trevor Scott

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    William R Spreen

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Liling L Warren

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,
    Allen D Roses

    GlaxoSmithKline, 5 Moore Drive, RTP, NC 27709, USA

    ,

    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 × 10-18) and is also observed in White females (n = 56, p = 6.8 × 10-6) and Hispanics (n = 104, p = 2.1 × 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.