Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility.

Full Abstract

The hypersensitivity (HSR) to abacavir (ABC) pharmacogenetics (PGx) program represents the progression from an exploratory discovery to a validated biomarker. Within the program, two retrospective PGx studies were conducted to identify HIV-1 patients at increased risk for ABC HSR, a treatment-limiting and potentially life-threatening adverse event. A strong statistical association between the major histocompatibility complex allele, HLA-B*5701, and clinically diagnosed ABC HSR was identified but varied between racial populations. Subsequently, ABC skin patch testing was introduced as a research tool to supplement clinical case ascertainment. In a randomized, prospective study evaluating the clinical utility of HLA-B*5701 screening, avoidance of ABC in HLA-B*5701-positive patients significantly reduced clinically diagnosed ABC HSR and eliminated patch test-positive ABC HSR. Finally, a retrospective PGx study supports the generalizability of the association across races. Prospective HLA-B*5701 screening should greatly reduce the incidence of ABC HSR by identifying patients at high risk for ABC HSR before they are treated.

Author information

Author/s: Hughes, A R (AR); Spreen, W R (WR); Mosteller, M (M); Warren, L L (LL); Lai, E H (EH); Brothers, C H (CH); Cox, C (C); Nelsen, A J (AJ); Hughes, S (S); Thorborn, D E (DE); Stancil, B (B); Hetherington, S V (SV); Burns, D K (DK); Roses, A D (AD);

Affiliation: GlaxoSmithKline Pharmacogenetics, Research Triangle Park, NC 27709, USA. arlene.r.hughes(-atsign-)gsk.com

Journal and publication information

Publication Type: Journal Article; Review

Journal: The pharmacogenomics journal (Pharmacogenomics J), published in United States. (Language: eng)

Reference: 2008-Dec; vol 8 (issue 6) : pp 365-74

Dates: Created 2008/11/14; Completed 2009/01/07;

PMID: 18332899, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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