Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

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Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.
Journal
Pharmacogenetics and Genomics
Author(s)
Lehmann D.S., Ribaudo H.J., Daar E.S., Gulick R.M., Haubrich R.H., Robbins G.K., de Bakker P.I., Haas D.W., McLaren P.J.
ISSN
1744-6880 (Electronic)
ISSN-L
1744-6872
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
25
Number
2
Pages
51-59
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
BACKGROUND: 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.
PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202.
RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) 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 CYP2B 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.
CONCLUSION: 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.
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07/02/2015 13:56
Last modification date
20/08/2019 16:01
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