Evidence map›Paper›PMID 25461247›Full record

SynthesisPharmacogenetics and genomics2015

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

David S Lehmann, Heather J Ribaudo, Eric S Daar, Roy M Gulick, Richard H Haubrich, Gregory K Robbins, Paul I W de Bakker, David W Haas, Paul J McLaren

Open access · greenAbstract readMeta-Analysis

PubMed Full text at PMC Publisher

In one paragraph

Synthesis in Pharmacogenetics and genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it

0cells of the map it votes in

8citing papers in PubMed, 1 pooled it

1.4field-weighted citation impact, top 19% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

Meta-analysis of the associations of CYP2B6-516G>T polymorphisms with efavirenz-induced central nervous system side effects and virological outcome in HIV-infected adults.The pharmacogenomics journal · 2020
Pooled it
Comprehensive Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Evaluation of Once-Daily Efavirenz 400 and 600 mg in Treatment-Naïve HIV-Infected Patients at 96 Weeks: Results of the ENCORE1 Study.Clinical pharmacokinetics · 2016
Trial
Association ofPharmacogenomics and personalized medicine · 2021
Article
Minding the gap in HIV host genetics: opportunities and challenges.Human genetics · 2020
Review
Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants.Therapeutic drug monitoring · 2017
Article
Host genetic variation and HIV disease: from mapping to mechanism.Immunogenetics · 2017
Review
Brief Report: CYP2B6 516G>T Minor Allele Protective of Late Virologic Failure in Efavirenz-Treated HIV-Infected Patients in Botswana.Journal of acquired immune deficiency syndromes (1999) · 2017
Observational
Role of pharmacogenetics in public health and clinical health care: a SWOT analysis.European journal of human genetics : EJHG · 2016
Review

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 4 countries.

David S LehmannaBrandeis University, Waltham bCenter for Biostatistics in AIDS Research, Harvard School of Public Health cDepartment of Medicine, Harvard Medical School, Boston, Massachusetts dLos Angeles Biomed Research Institute at Harbor-UCLA Medical Center, Torrance eDepartment of Medicine and Center for AIDS Research, University of California San Diego, San Diego, California fWeill Cornell Medical College, New York, New York gDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA hDepartments of Medical Genetics and Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands iSchool of Life Sciences, The Swiss Institute of Technology jInstitute of Microbiology University Hospital, University of Lausanne, Lausanne, Switzerland.

Heather J Ribaudo

Eric S Daar

Roy M Gulick

Richard H Haubrich

Gregory K Robbins

Paul I W de Bakker

David W Haas

Paul J McLaren

PharmacoGenetics (China) · CNCornell University · USHarvard University · USSan Francisco AIDS Foundation · USSwiss School of Public Health · CHVanderbilt University · US

Funding

Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026

$246.6M

WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008

$157.5M

AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010

$147.1M

Disparities in COVID Disease Severity and Outcomes in New York CityUL1TR002384 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI JULIANNE L IMPERATO-MCGINLEY · 2017 to 2026

$86.2M

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026

$78.6M

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026

$78.4M

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026

$76.9M

ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011

$74.2M

Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026

$74.0M

Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010

$71.9M

University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026

$71.8M

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011

$61.3M

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6 · The paper itself

Abstract

backgroundEfavirenz 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

methodsVirologic 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.

resultsMeta-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.

conclusionNo 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.

Indexed as

Genome-Wide Association StudyAbacavirAcquired Immunodeficiency SyndromeAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesDideoxynucleosidesDrug Therapy, CombinationHIV-1HIV InfectionsHumansPolymorphism, Single NucleotideRandomized Controlled Trials as TopicTreatment OutcomeAbacavirAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesDideoxynucleosidesefavirenz

Identifiers

PMID25461247

DOI10.1097/FPC.0000000000000106

PMCPMC4387236

OpenAlexW2078373467

What OpenQuestion holds

Textmetadata

LicenceTDM

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.