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

The Pharmacogenomics Journal volume 8, pages 365–374 (2008)Cite this article

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.

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Acknowledgements

We thank Drs Simon Mallal and Elizabeth Phillips for their contributions, independent of and in collaboration with GSK, to the identification of PGx markers associated with ABC HSR. We also thank the following GSK staff who provided important contributions to this research: Stephen LaFon, Lynn Marks, Trevor Scott, Martha Anne Moore, Keith Nangle, Stephen Haneline, Clive Bowman, Rukmini Balu, Mark Shaefer, Jaime Hernandez, Helen Steel, David Gordon, Lloyd Curtis, Amy Cutrell, Dominic Paes, Gaile Renegar and Tom Laughery. Finally, we thank the patients and health-care providers who generously contributed to the clinical studies described in this paper.

Author information

Author notes

  1. S V Hetherington

    Present address: 6Current address: Icagen Inc., Durham, NC 27703, USA.,

  2. A D Roses

    Present address: 7Current address: Institute for Genome Sciences and Policy, Duke University Medical Center and Fuqua School of Business, Durham, NC 27708, USA.,

Authors and Affiliations

  1. GlaxoSmithKline Pharmacogenetics, Research Triangle Park, NC, USA

    A R Hughes, M Mosteller, L L Warren, E H Lai, A J Nelsen, D K Burns & A D Roses

  2. Infectious Diseases Medicines Development Centre, Research Triangle Park, NC, USA

    W R Spreen, C H Brothers, B Stancil & S V Hetherington

  3. GlaxoSmithKline Pharmacogenetics, Harlow, UK

    C Cox

  4. Infectious Diseases Medicines Development Centre, Greenford, UK

    S Hughes

  5. Pharmaceuticals Europe, Brentford, UK

    D E Thorborn

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  1. A R Hughes
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Corresponding author

Correspondence to A R Hughes.

Additional information

Duality of interest

The authors are all current or former employees of GlaxoSmithKline, the manufacturer of ABC-containing medicines.

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Hughes, A., Spreen, W., Mosteller, M. et al. Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility. Pharmacogenomics J 8, 365–374 (2008). https://doi.org/10.1038/tpj.2008.3

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