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

TitleGenome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.
Publication TypeJournal Article
Year of Publication2015
AuthorsLehmann DS, Ribaudo HJ, Daar ES, Gulick RM, Haubrich RH, Robbins GK, DE Bakker PIW, Haas DW, McLaren PJ
JournalPharmacogenet Genomics
Volume25
Issue2
Pagination51-9
Date Published2015 Feb
ISSN1744-6880
KeywordsAcquired Immunodeficiency Syndrome, Anti-HIV Agents, Benzoxazines, Dideoxynucleosides, Drug Therapy, Combination, Genome-Wide Association Study, HIV Infections, HIV-1, Humans, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Treatment Outcome
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.

DOI10.1097/FPC.0000000000000106
Alternate JournalPharmacogenet. Genomics
PubMed ID25461247
PubMed Central IDPMC4387236
Grant ListAI 064086 / AI / NIAID NIH HHS / United States
AI 36214 / AI / NIAID NIH HHS / United States
AI-025859 / AI / NIAID NIH HHS / United States
AI-025868 / AI / NIAID NIH HHS / United States
AI-027658 / AI / NIAID NIH HHS / United States
AI-027661 / AI / NIAID NIH HHS / United States
AI-027666 / AI / NIAID NIH HHS / United States
AI-027675 / AI / NIAID NIH HHS / United States
AI-032782 / AI / NIAID NIH HHS / United States
AI-034853 / AI / NIAID NIH HHS / United States
AI-038858 / AI / NIAID NIH HHS / United States
AI-045008 / AI / NIAID NIH HHS / United States
AI-046370 / AI / NIAID NIH HHS / United States
AI-046376 / AI / NIAID NIH HHS / United States
AI-050409 / AI / NIAID NIH HHS / United States
AI-050410 / AI / NIAID NIH HHS / United States
AI-058740 / AI / NIAID NIH HHS / United States
AI-068634 / AI / NIAID NIH HHS / United States
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AI-077505 / AI / NIAID NIH HHS / United States
AI-54999 / AI / NIAID NIH HHS / United States
R01 AI077505 / AI / NIAID NIH HHS / United States
RR-000046 / RR / NCRR NIH HHS / United States
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RR-023561 / RR / NCRR NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
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