Evidence map›Paper›PMID 34729853›Full record

ArticlePharmacoepidemiology and drug safety2022

Do contemporary antiretrovirals increase the risk of end-stage liver disease? Signals from patients starting therapy in the North American AIDS Cohort Collaboration on Research and Design.

Jim Young, Vincent Lo Re, H Nina Kim, Timothy R Sterling, Keri N Althoff, Kelly A Gebo, M John Gill, Michael A Horberg, Angel M Mayor, Richard D Moore and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacoepidemiology and drug safety, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

13 authors at 8 institutions in 3 countries.

Jim YoungDivision of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, Quebec, Canada.ORCID 0000-0002-4314-3007
Vincent Lo ReDivision of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
H Nina KimDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Timothy R SterlingDivision of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Keri N AlthoffDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Kelly A GeboDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
M John GillDepartment of Medicine, University of Calgary, Calgary, Alberta, Canada.
Michael A HorbergKaiser Permanente Mid-Atlantic States, Mid-Atlantic Permanente Research Institute, Rockville, Maryland, USA.
Angel M MayorRetrovirus Research Center, Internal Medicine Department, School of Medicine, Universidad Central del Caribe, Bayamón, Puerto Rico, USA.
Richard D MooreDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Michael J SilverbergDivision of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Marina B KleinDivision of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, Quebec, Canada.
North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA
Johns Hopkins University · USKaiser Permanente · USMcGill University Health Centre · CACentral University of the Caribbean · PRUniversity of Calgary · CAUniversity of Pennsylvania · USUniversity of Washington · USVanderbilt University Medical Center · US

Funding

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
UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Unsolicited R24 for the CFAR-Network of Integrated Clinical Sciences, CNICSR24AI067039 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Michael S. Saag · 2006 to 2026
$99.4M
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALLORY O JOHNSON · 1988 to 2026
$93.6M
Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Latesha Ellen Elopre · 1988 to 2026
$84.1M
STATISTICAL AND DATA MANAGEMENT CENTERU01AI038855 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HUGHES, MICHAEL DAVID · 1996 to 2006
$78.1M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Studies of Ocular Complications of AIDS - Coordinating CenterU10EY008057 · NEI · JOHNS HOPKINS UNIVERSITY · PI VAN NATTA, MARK L · 1988 to 2012
$78.0M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Intramural NIH HHS Z01 CP010176NCATS NIH HHS KL2 TR000421NCATS NIH HHS KL2 TR002317NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR000083NCATS NIH HHS UL1 TR002378NCI NIH HHS N01 CP001004NCI NIH HHS N02 CP055504NCRR NIH HHS UL1 RR024131NEI NIH HHS K23 EY013707NEI NIH HHS U10 EY008052NEI NIH HHS U10 EY008057NEI NIH HHS U10 EY008067NHLBI NIH HHS U01 HL146192NHLBI NIH HHS U01 HL146193NHLBI NIH HHS U01 HL146194NHLBI NIH HHS U01 HL146201NHLBI NIH HHS U01 HL146202NHLBI NIH HHS U01 HL146203NHLBI NIH HHS U01 HL146204NHLBI NIH HHS U01 HL146205NHLBI NIH HHS U01 HL146208NHLBI NIH HHS U01 HL146240NHLBI NIH HHS U01 HL146241NHLBI NIH HHS U01 HL146242NHLBI NIH HHS U01 HL146245NHLBI NIH HHS U01 HL146333NIAAA NIH HHS R01 AA016893NIAAA NIH HHS U01 AA013566NIAAA NIH HHS U01 AA020790NIAAA NIH HHS U24 AA020794NIAID NIH HHS F31 AI124794NIAID NIH HHS K01 AI093197NIAID NIH HHS K01 AI131895NIAID NIH HHS K24 AI065298NIAID NIH HHS K24 AI118591NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI027763NIAID NIH HHS P30 AI027767NIAID NIH HHS P30 AI036219NIAID NIH HHS P30 AI050409NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI094189NIAID NIH HHS P30 AI110527NIAID NIH HHS R24 AI067039NIAID NIH HHS U01 AI038855NIAID NIH HHS U01 AI038858NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069434NIAID NIH HHS U01 AI069918NIA NIH HHS R01 AG053100NIDA NIH HHS F31 DA037788NIDA NIH HHS K24 DA000432NIDA NIH HHS R01 DA011602NIDA NIH HHS R01 DA012568NIDA NIH HHS R34 DA045592NIDA NIH HHS U01 DA036935NIGMS NIH HHS U54 GM133807NIMHD NIH HHS G12 MD007583NIMH NIH HHS P30 MH062246
6 · The paper itself

Abstract

purposeDespite effective antiretroviral therapy, rates of end-stage liver disease (ESLD) remain high. It is not clear whether contemporary antiretrovirals contribute to the risk of ESLD.

methodsWe included patients from cohorts with validated ESLD data in the North American AIDS Cohort Collaboration on Research and Design. Patients had to initiate antiretroviral therapy after 1 January 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a contemporary third (anchor) drug. Patients were followed until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow-up or 31 December 2015. We estimated associations between cumulative exposure to each drug and ESLD using a hierarchical Bayesian survival model with weakly informative prior distributions.

resultsAmong 10 564 patients included from 12 cohorts, 62 had an ESLD event. Of the nine anchor drugs, boosted protease inhibitors atazanavir and darunavir had the strongest signals for ESLD, with increasing hazard ratios (HR) and narrowing credible intervals (CrI), from a prior HR of 1.5 (95% CrI 0.32-7.1) per 5 year's exposure to posterior HRs respectively of 1.8 (95% CrI 0.82-3.9) and 2.0 (95% CrI 0.86-4.7). Both backbones and efavirenz showed no signal. Hepatitis C coinfection was the most important covariate risk factor (HR 4.4, 95% CrI 2.6-7.0).

conclusionsWhile contemporary antiretrovirals pose less risk for ESLD than hepatitis coinfection, atazanavir and darunavir had a toxicity signal. We show how hierarchical Bayesian modelling can be used to detect toxicity signals in cohort event monitoring data even with complex treatments and few events.

Indexed as

Acquired Immunodeficiency SyndromeEnd Stage Liver DiseaseHIV InfectionsBayes TheoremHumansNorth Americaadverse eventsBayesian statistical methodsend-stage liver diseasehepatocellular carcinomaHIVpharmacovigilance

Identifiers

PMID34729853
PMCPMC9089458
OpenAlexW3209378758

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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.