Evidence map›Paper›PMID 25746435›Full record

ArticlePloS one2015

p21(WAF1/CIP1) RNA expression in highly HIV-1 exposed, uninfected individuals.

Joshua Herbeck, Suvankar Ghorai, Lennie Chen, Charles R Rinaldo, Joseph B Margolick, Roger Detels, Lisa Jacobson, Steven Wolinsky, James I Mullins

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. 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
0.3field-weighted citation impact, top 41% 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, 4 citations in OpenAlex.

  1. Review
  2. 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

9 authors at 5 institutions in 1 country.

Joshua HerbeckDepartment of Global Health, University of Washington, Seattle, Washington, United States of America.
Suvankar GhoraiDepartment of Microbiology, University of Washington, Seattle, Washington, United States of America.
Lennie ChenDepartment of Microbiology, University of Washington, Seattle, Washington, United States of America.
Charles R RinaldoUniversity of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Joseph B MargolickDepartment of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Roger DetelsDepartment of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America.
Lisa JacobsonDepartment of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Steven WolinskyDepartment of Medicine, Northwestern University, Chicago, Illinois, United States of America.
James I MullinsDepartment of Microbiology, University of Washington, Seattle, Washington, United States of America.
University of Washington · USJohns Hopkins University · USNorthwestern University · USUniversity of California, Los Angeles · USUniversity of Pittsburgh · US

Funding

NATURAL HISTORY OF AIDS IN HOMOSEXUAL MENU01AI035040 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DETELS, ROGER, MARTINEZ-MAZA, OTONIEL · 1993 to 2018
$75.2M
University of Pittsburgh Multicenter AIDS Cohort Study (MACS)U01AI035041 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARTINSON, JEREMY JAMES, RINALDO, CHARLES R · 1993 to 2018
$71.4M
MULTICENTER AIDS COHORT STUDYU01AI035039 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 1993 to 2018
$66.4M
Multicenter Aids Cohort Study- Part B (Baltimore Site)U01AI035042 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T, MARGOLICK, JOSEPH B. · 1993 to 2018
$61.5M
UCLA Rapid, Relevant, Rigorous Implementation Science HubP30MH058107 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAPHAEL J LANDOVITZ · 1997 to 2026
$53.5M
Center for the Analysis & Management of the Multicenter AIDS Cohort StudyUM1AI035043 · NIAID · JOHNS HOPKINS UNIVERSITY · PI D'SOUZA, GYPSYAMBER, JACOBSON, LISA P · 2012 to 2018
$20.7M
Viral Determinants of HIV-1 Transmission in African HeterosexualsP01AI057005 · NIAID · UNIVERSITY OF WASHINGTON · PI COREY, LAWRENCE · 2003 to 2014
$20.5M
NIAID NIH HHS P01 AI057005NIAID NIH HHS U01 AI035039NIAID NIH HHS U01 AI035040NIAID NIH HHS U01 AI035041NIAID NIH HHS U01 AI035042NIAID NIH HHS U01-AI35039NIAID NIH HHS U01-AI35040NIAID NIH HHS U01-AI35041NIAID NIH HHS U01-AI35042NIAID NIH HHS UM1 AI035043NIAID NIH HHS UM1-AI35043NIMH NIH HHS P30 MH058107PHS HHS R37-047734
6 · The paper itself

Abstract

Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21WAF1/CIP1 (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R2 = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1.

Indexed as

HIV SeronegativitySexual PartnersCyclin-Dependent Kinase Inhibitor p21HIV-1HIV InfectionsHumansRisk FactorsRNAUnsafe SexCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21RNA

Identifiers

PMID25746435
PMCPMC4352077
OpenAlexW2091351383

What OpenQuestion holds

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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.