Evidence map›Paper›PMID 26180834›Full record

ArticleOpen forum infectious diseases2015

Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia.

Saran Vardhanabhuti, Heather J Ribaudo, Raphael J Landovitz, Ighovwerha Ofotokun, Jeffrey L Lennox, Judith S Currier, Lana M Olson, David W Haas

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Open forum infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00851799 (Cardiovascular, Anthropometric, and Skeletal Effects of Antiretroviral Therapy), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 3% 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.

NCT00851799 completednot on this map

Cardiovascular, Anthropometric, and Skeletal Effects of Antiretroviral Therapy (ART) Initiation With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Plus Atazanavir/Ritonavir (ATV/r), Darunavir/Ritonavir (DRV/r), or Raltegravir (RAL): Metabolic Substudy of A5257

TypeobservationalSponsorAdvancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsRan2009 to 2013Enrolled334ConditionsHIV InfectionArmsEmtricitabine/tenofovir disoproxil fumarate, Ritonavir, Atazanavir, Raltegravir, Darunavir
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Guideline
  2. Trial
  3. Trial
  4. Genetic Testing in Clinical Settings.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2018
    Review
  5. Article
  6. Observational
  7. Review
  8. Article
  9. Observational
  10. 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

8 authors at 3 institutions in 1 country.

Saran VardhanabhutiStatistical Data Analysis Center , Harvard School of Public Health , Boston, Massachusetts.
Heather J RibaudoStatistical Data Analysis Center , Harvard School of Public Health , Boston, Massachusetts.
Raphael J LandovitzUCLA Center for Clinical AIDS Research and Education , Los Angeles, California.
Ighovwerha OfotokunEmory University School of Medicine , Atlanta, Georgia.
Jeffrey L LennoxEmory University School of Medicine , Atlanta, Georgia.
Judith S CurrierUCLA Center for Clinical AIDS Research and Education , Los Angeles, California.
Lana M OlsonVanderbilt University School of Medicine , Nashville, Tennessee.
David W HaasVanderbilt University School of Medicine , Nashville, Tennessee.
APLA Health · USEmory University · USVanderbilt 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
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
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
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 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 Carlos del Rio · 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 RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
NCATS NIH HHS UL1 TR000445NCRR 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 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 U01 AI069513NIAID NIH HHS U01 AI069532NIAID NIH HHS U01 AI069556NIAID 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 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 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 AI069532NIAID NIH HHS UM1 AI069556NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

Background.  Some patients are not prescribed atazanavir because of concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group Study A5257. Methods.  Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results.  Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals [CIs]) were 20% (CI, 9%-36%) in Black, 60% (CI, 32%-84%) in White, and 29% (CI, 8%-58%) in Hispanic participants; negative predictive values were 97% (CI, 93%-99%), 95% (CI, 90%-98%), and 97% (CI, 90%-100%), respectively. Conclusions.  Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race or ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race and ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat.

Indexed as

atazanavirHIVpharmacogenomicspharmacokineticsUGT1A1

Identifiers

PMID26180834
PMCPMC4498287
OpenAlexW2140028712

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.