Evidence map›Paper›PMID 23014521›Full record

ArticleAIDS (London, England)2012

Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.

Angela M Mexas, Erin H Graf, Matthew J Pace, Jianqing J Yu, Emmanouil Papasavvas, Livio Azzoni, Michael P Busch, Michele Di Mascio, Andrea S Foulkes, Stephen A Migueles and 2 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in AIDS (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02227277 (Towards Eradication), which is not on this map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.9field-weighted citation impact, top 4% 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.

NCT02227277 phase2unknown statusnot on this mapstarted 2015, after this paper: background citation

Towards Eradication: Reducing Proviral HIV DNA With Interferon-a Immunotherapy

TypeinterventionalSponsorThe Wistar InstituteRan2015 to 2018Enrolled54ConditionsHIV, HIV/AIDSArmsPeg-IFN-α2b
3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 95 citations in OpenAlex.

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4 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

12 authors at 4 institutions in 1 country.

Angela M MexasDivision of Transfusion Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Erin H Graf
Matthew J Pace
Jianqing J Yu
Emmanouil Papasavvas
Livio Azzoni
Michael P Busch
Michele Di Mascio
Andrea S Foulkes
Stephen A Migueles
Luis J Montaner
Una O'Doherty
University of Pennsylvania · USThe Wistar Institute · USUniversity of California, San Francisco · USUniversity of Massachusetts Amherst · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
Antiviral activity of Peg-IFN alpha in chronic HIV-1U01AI065279 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J · 2005 to 2009
$2.8M
Effect of Treg Cells on CD4+Th Immune Responses During Acute FIV InfectionK08AI073102 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI MEXAS, ANGELA M · 2007 to 2011
$647k
Ongoing replication may occur on HAARTR21AI087461 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI O'DOHERTY, UNA T · 2010 to 2011
$431k
HIV Restriction in CD4+ T cells: Host and Viral FactorsK02AI078766 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI O'DOHERTY, UNA T · 2008 to 2012
$405k
NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA10815NIAID NIH HHS 5K08AI073102NIAID NIH HHS K02 AI078766NIAID NIH HHS K02AI078766NIAID NIH HHS K08 AI073102NIAID NIH HHS P30 AI027763NIAID NIH HHS P30 AI 045008NIAID NIH HHS P30 AI045008NIAID NIH HHS R21 AI087461NIAID NIH HHS T32 AI007632NIAID NIH HHS U01 AI065279NIAID NIH HHS U01AI065279
6 · The paper itself

Abstract

objectivesInterest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials.

designTo determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir size and ongoing replication, these parameters were measured during the first year of ART, during long-term effective ART, and during a clinical trial aimed at targeting reservoirs.

methodsTotal and integrated HIV DNA were measured in patient samples using quantitative PCR techniques. CD4(+)T cell counts and plasma viremia were also monitored.

resultsUnintegrated HIV DNA became undetectable during the first year of ART. Total and integrated HIV DNA levels were generally equal in well controlled patients on ART, and low-level plasma viremia correlated best with integration measures. Finally, patients who controlled plasma viremia (<400 copies/ml) during interferon-α monotherapy exhibited a decrease in the level of integrated but not total HIV DNA and a rise in the ratio of total to integrated HIV DNA over time.

conclusionOur findings suggest that appearance of unintegrated HIV DNA reflects residual HIV expression and de-novo reverse transcription, providing insight into the mechanism by which interferon-α reduces the HIV reservoir. We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV.

Indexed as

AdultAnti-HIV AgentsBiomarkersCD4 Lymphocyte CountCD4-Positive T-LymphocytesClinical Trials as TopicDisease ReservoirsDNA, ViralFemaleHIV-1HIV InfectionsHumansInterferon-alphaMaleMiddle AgedPolymerase Chain ReactionAnti-HIV AgentsBiomarkersDNA, ViralInterferon-alpha

Identifiers

PMID23014521
PMCPMC4692807
OpenAlexW2072820915

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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.