Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Lehmann, David S.; Ribaudo, Heather J.; Daar, Eric S.; Gulick, Roy M.; Haubrich, Richard H.; Robbins, Gregory K.; de Bakker, Paul I.W.; Haas, David W.; McLaren, Paul J.
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 2(2015:Feb.)
• Publication Date: 2015-02
• Subjects: Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000106
• Languages: English
• ISSNs: 1744-6872

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols.</p> </sec> <sec> <title>Participants and methods</title> <p>Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (<italic>n</italic>=1596) or abacavir-containing (<italic>n</italic>=786) regimens in ACTG protocols 384, A5142, A5095, and A5202.</p> </sec> <sec> <title>Results</title> <p>Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (<italic>P</italic><5×10<sup>–8</sup>) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on <italic>CYP2B</italic> genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition.</p> </sec> <sec> <title>Conclusion</title> <p>No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.</p> </sec> </abstract>