Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing

MA Martin,¹ TE Klein,² BJ Dong,³ M Pirmohamed,⁴ DW Haas,^5–7 and DL Kroetz¹

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Abstract

Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ∼6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype.

The purpose of this guideline is to provide information that will allow the interpretation of clinical HLA-B genotype tests so that the results can be used to guide the use of abacavir for the treatment of HIV. Detailed guidelines regarding selection of appropriate antiretroviral therapy based on patient demographics and clinical measurements, viral resistance testing, and cost-effectiveness analyses, are beyond the scope of this article but are available at http://aidsinfo.nih.gov. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on http://www.pharmgkb.org to reflect new developments in the field.

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FOCUSED LITERATURE REVIEW

A systematic search of the literature focused on HLA-B genotype and abacavir use (see Supplementary Data online); reviews– were relied on to summarize much of the earlier literature.