Evidence map›Paper›PMID 23503447›Full record

Trial reportTherapeutic drug monitoring2013

Discordant associations between SLCO1B1 521T→C and plasma levels of ritonavir-boosted protease inhibitors in AIDS clinical trials group study A5146.

Xinyan Zhang, Camlin Tierney, Mary Albrecht, Lisa M Demeter, Gene Morse, Robin DiFrancesco, Carrie Dykes, Hongyu Jiang, David W Haas

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Therapeutic drug monitoring, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Pharmacogenetics of drug-metabolizing enzymes in US Hispanics.Drug metabolism and personalized therapy · 2015
    Review
  7. 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 5 institutions in 1 country.

Xinyan ZhangCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.
Camlin Tierney
Mary Albrecht
Lisa M Demeter
Gene Morse
Robin DiFrancesco
Carrie Dykes
Hongyu Jiang
David W Haas
Cancer Research And Biostatistics · USUniversity at Buffalo, State University of New York · USUniversity of Rochester · USBeth Israel Deaconess Medical Center · USHarvard University · 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
LOC-IMPAACT Leadership GroupPharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the USUM1AI068632 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI Sharon A Nachman · 2011 to 2026
$278.1M
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
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
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
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
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitUM1AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TIMOTHY J. WILKIN · 2012 to 2026
$50.4M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024996 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2007 to 2011
$49.6M
NCATS NIH HHS TR000445NCATS NIH HHS UL1 TR000457NCRR NIH HHS M01 RR000044NCRR NIH HHS M01 RR000095NCRR NIH HHS RR00044NCRR NIH HHS RR024996NCRR NIH HHS RR025747NCRR NIH HHS UL1 RR024996NCRR NIH HHS UL1 RR025747NIAID NIH HHS AI050409NIAID NIH HHS AI050410NIAID NIH HHS AI062435NIAID NIH HHS AI069415NIAID NIH HHS AI069419NIAID NIH HHS AI069423NIAID NIH HHS AI069428NIAID NIH HHS AI069434NIAID NIH HHS AI069439NIAID NIH HHS AI069452NIAID NIH HHS AI069470NIAID NIH HHS AI069471NIAID NIH HHS AI069472NIAID NIH HHS AI069474NIAID NIH HHS AI069477NIAID NIH HHS AI069484NIAID NIH HHS AI069494NIAID NIH HHS AI069495NIAID NIH HHS AI069502NIAID NIH HHS AI069511NIAID NIH HHS AI069513NIAID NIH HHS AI069556NIAID NIH HHS AI073961NIAID NIH HHS AI077505NIAID NIH HHS AI25903NIAID NIH HHS AI27757NIAID NIH HHS AI38858NIAID NIH HHS AI46370NIAID NIH HHS AI51966NIAID NIH HHS AI54999NIAID NIH HHS AI68634NIAID NIH HHS AI69418NIAID NIH HHS AI69419NIAID NIH HHS AI69432NIAID NIH HHS AI69450NIAID NIH HHS AI69467NIAID NIH HHS AI69501NIAID NIH HHS K01 AI062435NIAID NIH HHS K24 AI051966NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI050409NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI054999NIAID NIH HHS P30 AI073961NIAID NIH HHS R01 AI077505NIAID NIH HHS U01 AI025903NIAID NIH HHS U01 AI027661NIAID NIH HHS U01 AI038858NIAID NIH HHS U01 AI046370NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01AI068636NIAID NIH HHS U01 AI069415NIAID NIH HHS U01 AI069418NIAID NIH HHS U01 AI069419NIAID NIH HHS U01 AI069423NIAID NIH HHS U01 AI069428NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069434NIAID NIH HHS U01 AI069439NIAID NIH HHS U01 AI069450NIAID NIH HHS U01 AI069452NIAID NIH HHS U01 AI069467NIAID 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 U01AI069511NIAID NIH HHS U01 AI069513NIAID NIH HHS U01 AI069556NIAID NIH HHS UM1 AI068632NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069415NIAID NIH HHS UM1 AI069418NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069428NIAID NIH HHS UM1 AI069432NIAID NIH HHS UM1 AI069434NIAID NIH HHS UM1 AI069439NIAID NIH HHS UM1 AI069450NIAID NIH HHS UM1 AI069452NIAID NIH HHS UM1 AI069467NIAID 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 AI069556NINDS NIH HHS NS32228NINDS NIH HHS R01 NS032228NINDS NIH HHS U01 NS032228PHS HHS A1069424PHS HHS A1069447PHS HHS AL069532PHS HHS AL27665PHS HHS BRS-ACURE-06-00140-T001
6 · The paper itself

Abstract

objectiveAmong HIV-positive patients prescribed ritonavir-boosted lopinavir, SLCO1B1 521T→C (rs4149056) is associated with increased plasma lopinavir exposure. Protease inhibitors (PIs) are also substrates for cytochrome P450 (CYP) 3A and ABCB1, which are induced by NR1I2. We characterized relationships between ABCB1, CYP3A4, CYP3A5, NR1I2, and SLCO1B1 polymorphisms and trough PI concentrations among AIDS Clinical Trials Group study A5146 participants.

methodsAt study entry, subjects with virologic failure on PI-containing regimens initiated new ritonavir-boosted PI regimens. We studied associations between week 2 PI plasma trough concentrations and 143 polymorphisms in these genes, including 4 targeted polymorphisms.

resultsAmong 275 subjects with both drug concentrations and genetic data, allelic frequencies of SLCO1B1 521T→C were 15%, 1%, and 8% in whites, blacks, and Hispanics, respectively. Further analyses were limited to 268 white, black, or Hispanic subjects who initiated ritonavir-boosted lopinavir (n = 98), fosamprenavir (n = 69), or saquinavir (n = 99). Of targeted polymorphisms, SLCO1B1 521T→C tended to be associated with higher lopinavir concentrations, with a 1.38-fold increase in the mean per C allele (95% confidence interval, 0.97-1.96; n = 98; P = 0.07). With fosamprenavir, SLCO1B1 521T→C was associated with lower amprenavir concentrations, with a 35% decrease in the mean per C allele (geometric mean ratio 0.65; 95% confidence interval, 0.44-0.94; n = 69; adjusted P = 0.02). There was no significant association with saquinavir concentrations, and none of the remaining 139 exploratory polymorphisms were statistically significant after correcting for multiple comparisons.

conclusionsWith ritonavir-boosted PIs, a SLCO1B1 polymorphism that predicts higher lopinavir trough concentrations seems to predict lower amprenavir trough concentrations. The mechanism underlying this discordant association is uncertain.

Indexed as

Acquired Immunodeficiency SyndromeAdultFemaleGenetic Association StudiesHIV Protease InhibitorsHumansLinkage DisequilibriumLiver-Specific Organic Anion Transporter 1MaleMiddle AgedOrganic Anion TransportersRitonavirHIV Protease InhibitorsLiver-Specific Organic Anion Transporter 1Organic Anion TransportersRitonavirSLCO1B1 protein, human

Identifiers

PMID23503447
PMCPMC3603284
OpenAlexW2321368561

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Registered trials

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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.