Evidence map›Paper›PMID 29847509›Full record

Trial reportPharmacogenetics and genomics2018

Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events.

David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Paul E Sax, Eric S Daar, Gene D Morse and 2 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pharmacogenetics and genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Efavirenz Pharmacogenetics and Weight Gain Following Switch to Integrase Inhibitor-Containing Regimens.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
    Trial
  2. Trial
  3. Article
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

12 authors at 9 institutions in 1 country.

David W HaasDepartment of Medicine, Vanderbilt University School of Medicine.
Yuki BradfordDepartment of Genetics.
Anurag VermaDepartment of Genetics.
Shefali S VermaDepartment of Genetics.
Joseph J EronDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Roy M GulickDepartment of Medicine, Weill Cornell Medicine, New York City.
Sharon A RiddlerDepartment of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Paul E SaxDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Eric S DaarDavid Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute, Los Angeles, California.
Gene D MorseUniversity at Buffalo, SUNY, Buffalo, New York.
Edward P AcostaUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.
Marylyn D RitchieDepartment of Genetics.
University of Pennsylvania · USBrigham and Women's Hospital · USCornell University · USMeharry Medical College · USThe Lundquist Institute · USUniversity at Buffalo, State University of New York · USUniversity of Alabama at Birmingham · USUniversity of North Carolina at Chapel Hill · USUniversity of Pittsburgh · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
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
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
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
STATISTICAL AND DATA MANAGEMENT CENTERU01AI038855 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HUGHES, MICHAEL DAVID · 1996 to 2006
$78.1M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
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
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002243NCATS NIH HHS UL1 TR002384NCRR NIH HHS M01 RR000046NCRR NIH HHS M01 RR000051NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR024160NCRR NIH HHS UL1 RR024996NCRR NIH HHS UL1 RR025747NCRR NIH HHS UL1 RR025777NIAID NIH HHS P30 AI045008NIAID NIH HHS P30 AI050409NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI054907NIAID NIH HHS P30 AI073961NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI058740NIAID NIH HHS R01 AI077505NIAID NIH HHS U01 AI025859NIAID NIH HHS U01 AI027658NIAID NIH HHS U01 AI027661NIAID NIH HHS U01 AI027666NIAID NIH HHS U01 AI027675NIAID NIH HHS U01 AI032782NIAID NIH HHS U01 AI034853NIAID NIH HHS U01 AI038855NIAID NIH HHS U01 AI038858NIAID NIH HHS U01 AI046370NIAID NIH HHS U01 AI046376NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01 AI069415NIAID NIH HHS U01 AI069418NIAID NIH HHS U01 AI069419NIAID NIH HHS U01 AI069423NIAID NIH HHS U01 AI069424NIAID NIH HHS U01 AI069428NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069434NIAID NIH HHS U01 AI069439NIAID NIH HHS U01 AI069447NIAID NIH HHS U01 AI069450NIAID NIH HHS U01 AI069452NIAID NIH HHS U01 AI069465NIAID NIH HHS U01 AI069470NIAID NIH HHS U01 AI069471NIAID NIH HHS U01 AI069472NIAID NIH HHS U01 AI069474NIAID NIH HHS U01 AI069477NIAID NIH HHS U01 AI069484NIAID NIH HHS U01 AI069494NIAID NIH HHS U01 AI069495NIAID NIH HHS U01 AI069501NIAID NIH HHS U01 AI069502NIAID NIH HHS U01 AI069511NIAID NIH HHS U01 AI069513NIAID NIH HHS U01 AI069532NIAID NIH HHS U01 AI069556NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069415NIAID NIH HHS UM1 AI069418NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069428NIAID NIH HHS UM1 AI069432NIAID NIH HHS UM1 AI069434NIAID NIH HHS UM1 AI069439NIAID NIH HHS UM1 AI069447NIAID NIH HHS UM1 AI069450NIAID NIH HHS UM1 AI069452NIAID NIH HHS UM1 AI069465NIAID NIH HHS UM1 AI069470NIAID NIH HHS UM1 AI069471NIAID NIH HHS UM1 AI069472NIAID NIH HHS UM1 AI069474NIAID NIH HHS UM1 AI069477NIAID NIH HHS UM1 AI069484NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI069495NIAID NIH HHS UM1 AI069501NIAID NIH HHS UM1 AI069502NIAID NIH HHS UM1 AI069511NIAID NIH HHS UM1 AI069513NIAID NIH HHS UM1 AI069532NIAID NIH HHS UM1 AI069556NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

objectiveWe characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND

methodsFour clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry.

resultsAnalyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)).

conclusionEfavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics.

Indexed as

Polymorphism, Single NucleotideAdultAlkynesBenzoxazinesCentral Nervous System DiseasesCyclopropanesFemaleGenomicsGenotypeHIVHIV InfectionsHumansMaleMiddle AgedNeurotransmitter Transport ProteinsPharmacogenomic TestingAlkynesBenzoxazinesCyclopropanesefavirenzNeurotransmitter Transport ProteinsReceptors, NeurotransmitterReverse Transcriptase Inhibitors

Identifiers

PMID29847509
PMCPMC6010221
OpenAlexW2805554142

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.