Evidence map›Paper›PMID 23175380›Full record

ArticleJournal of virology2013

An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral treatment suggests proliferation of HIV-infected cells.

Thor A Wagner, Jen L McKernan, Nicole H Tobin, Ken A Tapia, James I Mullins, Lisa M Frenkel

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

74 citing papers in PubMed, 97 citations in OpenAlex.

  1. HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014
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  16. Substantial uneven proliferation of CD4Journal of virus eradication · 2022
    Article
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  19. Article
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14 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

6 authors at 1 institution in 1 country.

Thor A WagnerSeattle Children's Research Institute, Seattle, Washington, USA. thor.wagner@seattlechildrens.org
Jen L McKernan
Nicole H Tobin
Ken A Tapia
James I Mullins
Lisa M Frenkel
University of Washington · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
ZIPRASIDONE IN NORMAL HEPATIC FUNCTION SUBJECTS &IN HEPATIC DYSFUCTIN SUBJECTSM01RR000037 · NCRR · UNIVERSITY OF WASHINGTON · PI MCDONALD, RUTH C · 1985 to 2007
$33.8M
Viral Determinants of HIV-1 Transmission in African HeterosexualsP01AI057005 · NIAID · UNIVERSITY OF WASHINGTON · PI COREY, LAWRENCE · 2003 to 2014
$20.5M
ACADEMIC PEDIATRIC INFECTIOUS DISEASET32HD007233 · NICHD · SEATTLE CHILDREN'S HOSPITAL · PI KEVIN B URDAHL · 1985 to 2026
$6.7M
HIV-1 evolution in the female genital tract and trafficking to the bloodR01AI091550 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2011 to 2015
$1.9M
Persistent HIV-1 Replication in the Respiratory Tract Despite ARTK23AI077357 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI WAGNER, THOR ANDREW · 2008 to 2012
$647k
Reservoirs of drug-resistant HIV-1R21AI058723 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2004 to 2004
$229k
Persistent Replication of HIV-1 in ChildrenK23AI058683 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI TOBIN, NICOLE H · 2004 to 2005
$173k
NCRR NIH HHS M01 RR000037NCRR NIH HHS M01RR-00037NIAID NIH HHS K23 AI058683NIAID NIH HHS K23 AI077357NIAID NIH HHS P01 AI057005NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI27757NIAID NIH HHS R01 AI091550NIAID NIH HHS R21 AI058723NICHD NIH HHS T32 HD007233
6 · The paper itself

Abstract

Understanding how HIV-1 persists during effective antiretroviral therapy (ART) should inform strategies to cure HIV-1 infection. We hypothesize that proliferation of HIV-1-infected cells contributes to persistence of HIV-1 infection during suppressive ART. This predicts that identical or monotypic HIV-1 DNA sequences will increase over time during ART. We analyzed 1,656 env and pol sequences generated following single-genome amplification from the blood and sputum of six individuals during long-term suppressive ART. The median proportion of monotypic sequences increased from 25.0% prior to ART to 43.2% after a median of 9.8 years of suppressive ART. The proportion of monotypic sequences was estimated to increase 3.3% per year (95% confidence interval, 2.3 to 4.4%; P < 0.001). Drug resistance mutations were not more common in the monotypic sequences, arguing against viral replication during times with lower antiretroviral concentrations. Bioinformatic analysis found equivalent genetic distances of monotypic and nonmonotypic sequences from the predicted founder virus sequence, suggesting that the relative increase in monotypic variants over time is not due to selective survival of cells with viruses from the time of acute infection or from just prior to ART initiation. Furthermore, while the total HIV-1 DNA load decreased during ART, the calculated concentration of monotypic sequences was stable in children, despite growth over nearly a decade of observation, consistent with proliferation of infected CD4(+) T cells and slower decay of monotypic sequences. Our findings suggest that proliferation of cells with proviruses is a likely mechanism of HIV-1 DNA persistence, which should be considered when designing strategies to eradicate HIV-1 infection.

Indexed as

AdolescentAnti-Retroviral AgentsBloodCell ProliferationChildCluster AnalysisDNA, Viralenv Gene Products, Human Immunodeficiency VirusGenotypeHIV-1HIV InfectionsHumansMolecular Sequence Datapol Gene Products, Human Immunodeficiency VirusProspective StudiesSequence Analysis, DNAAnti-Retroviral AgentsDNA, Viralenv Gene Products, Human Immunodeficiency Viruspol Gene Products, Human Immunodeficiency Virus

Identifiers

PMID23175380
PMCPMC3554159
OpenAlexW2072164469

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.