Evidence map›Paper›PMID 24755434›Full record

ArticleThe Journal of infectious diseases2014

Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection.

Peter W Hunt, Elizabeth Sinclair, Benigno Rodriguez, Carey Shive, Brian Clagett, Nicholas Funderburg, Janet Robinson, Yong Huang, Lorrie Epling, Jeffrey N Martin and 5 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000168 (Studies of Ocular Complications of AIDS), which is not on this map. Cited by 339 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
339citing papers in PubMed, 1 pooled it
24.0field-weighted citation impact, top 1% 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.

NCT00000168 completednot on this map

Studies of Ocular Complications of AIDS (SOCA)

TypeobservationalSponsorJohns Hopkins Bloomberg School of Public HealthRan1998 to 2013Enrolled2,392ConditionsHIV Infections, Acquired Immunodeficiency Syndrome, Cytomegalovirus Retinitis
3 · Its place in the literature

Who cites it

339 citing papers in PubMed, 1 synthesis or guideline pooled it, 472 citations in OpenAlex.

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  7. Interleukin 6 Blockade With Tocilizumab Diminishes Indices of Inflammation That Are Linked to Mortality in Treated Human Immunodeficiency Virus Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
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  8. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
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  13. Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
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279 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 1 country.

Peter W HuntDepartment of Medicine, University of California San Francisco.
Elizabeth SinclairDepartment of Medicine, University of California San Francisco.
Benigno RodriguezDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio.
Carey ShiveDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio.
Brian ClagettDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio.
Nicholas FunderburgSchool of Health and Rehabilitation Sciences, Medical Laboratory Science Division, Ohio State University, Columbus.
Janet RobinsonDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio.
Yong HuangDepartment of Bioengineering and Therapeutic Sciences.
Lorrie EplingDepartment of Medicine, University of California San Francisco.
Jeffrey N MartinDepartment of Medicine, University of California San Francisco Department of Epidemiology and Biostatistics, University of California San Francisco.
Steven G DeeksDepartment of Medicine, University of California San Francisco.
Curtis L MeinertDepartment of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Mark L Van NattaDepartment of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Douglas A JabsDepartment of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland Departments of Ophthalmology and Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York.
Michael M LedermanDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio.
Case Western Reserve University · USUniversity of California, San Francisco · USJohns Hopkins University · USIcahn School of Medicine at Mount Sinai · USThe Ohio State 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
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
UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
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 STEVEN Grant DEEKS · 1988 to 2026
$93.6M
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
Ujima Mentoring ProgramP30MH062246 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Sheri Ann Lippman · 2001 to 2026
$57.4M
Specimen Acquisition and Distribution CoreP01AI076174 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI LANDAY, ALAN L · 2008 to 2012
$10.9M
Studies of Ocular Complications of AIDS - Chairman's OfficeU10EY008052 · NEI · JOHNS HOPKINS UNIVERSITY · PI JABS, DOUGLAS A · 1988 to 2012
$8.0M
Studies of Ocular Complications of AIDS - Reading CenterU10EY008067 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI DANIS, RONALD · 1988 to 2012
$3.2M
The impact of early antiretroviral therapy on HIV persistence and inflammationR01AI087145 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT · 2009 to 2010
$1.6M
NCATS NIH HHS UL1 TR000004NCRR NIH HHS UL1 RR024131NCRR NIH HHS UL1RR024131NEI NIH HHS U10 EY008052NEI NIH HHS U10EY008052NEI NIH HHS U10 EY008057NEI NIH HHS U10EY008057NEI NIH HHS U10 EY008067NEI NIH HHS U10EY008067NHLBI NIH HHS 1K99HL108743NHLBI NIH HHS K99 HL108743NHLBI NIH HHS R00 HL108743NIAID NIH HHS K24 AI069994NIAID NIH HHS K24AI069994NIAID NIH HHS P01 AI076174NIAID NIH HHS P01AI076174NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI087145NIAID NIH HHS R21 AI087035NIAID NIH HHS R24 AI067039NIAID NIH HHS R24AI067039NIAID NIH HHS R56 AI100765NIAID NIH HHS R56AI100765NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIMH NIH HHS P30 MH062246NIMH NIH HHS P30MH62246
6 · The paper itself

Abstract

backgroundWhile inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.

methodsWe assessed immunologic predictors of mortality in a case-control study within the Longitudinal Study of the Ocular Complications of AIDS (LSOCA), using conditional logistic regression. Sixty-four case patients who died within 12 months of treatment-mediated viral suppression were each matched to 2 control individuals (total number of controls, 128) by duration of antiretroviral therapy-mediated viral suppression, nadir CD4(+) T-cell count, age, sex, and prior cytomegalovirus (CMV) retinitis. A similar secondary analysis was conducted in the SCOPE cohort, which had participants with less advanced immunodeficiency.

resultsPlasma gut epithelial barrier integrity markers (intestinal fatty acid binding protein and zonulin-1 levels), soluble CD14 level, kynurenine/tryptophan ratio, soluble tumor necrosis factor receptor 1 level, high-sensitivity C-reactive protein level, and D-dimer level all strongly predicted mortality, even after adjustment for proximal CD4(+) T-cell count (all P ≤ .001). A higher percentage of CD38(+)HLA-DR(+) cells in the CD8(+) T-cell population was a predictor of mortality before (P = .031) but not after (P = .10) adjustment for proximal CD4(+) T-cell count. Frequencies of senescent (defined as CD28(-)CD57(+) cells), exhausted (defined as PD1(+) cells), naive, and CMV-specific T cells did not predict mortality.

conclusionsGut epithelial barrier dysfunction, innate immune activation, inflammation, and coagulation-but not T-cell activation, senescence, and exhaustion-independently predict mortality in individuals with treated HIV infection with a history of AIDS and are viable targets for interventions.

Indexed as

AdultBlood CoagulationCase-Control StudiesFemaleHIV InfectionsHumansImmunity, InnateInflammationIntestinal MucosaLymphocyte ActivationMaleMiddle AgedT-Lymphocytesantiretroviral therapyCD28CD38CD57cytomegalovirusD-dimergut epithelial cell barrierHIVHLA-DRhsCRPIL-6immune activationintestinal fatty acid binding protein (I-FABP)mortalitysCD14T-cell activationzonulin-1

Identifiers

PMID24755434
PMCPMC4192038
OpenAlexW2098836196

What OpenQuestion holds

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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.