Evidence map›Paper›PMID 37443365›Full record

ArticleNature communications2023

Impact of misclassified defective proviruses on HIV reservoir measurements.

Daniel B Reeves, Christian Gaebler, Thiago Y Oliveira, Michael J Peluso, Joshua T Schiffer, Lillian B Cohn, Steven G Deeks, Michel C Nussenzweig

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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

32 citing papers in PubMed.

  1. Article
  2. The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

8 authors.

Daniel B ReevesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. dreeves@fredhutch.org.ORCID 0000-0001-5684-9538
Christian GaeblerLaboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Thiago Y OliveiraLaboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-2654-0879
Michael J PelusoDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, UCSF, San Francisco, CA, USA.ORCID 0000-0003-0585-6230
Joshua T SchifferVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0002-2598-1621
Lillian B CohnVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Steven G DeeksDivision of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, UCSF, San Francisco, CA, USA.ORCID 0000-0001-6371-747X
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.ORCID 0000-0003-0592-8564

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6M
REACH: Research Enterprise to Advance a Cure for HIVUM1AI164565 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Marina Caskey, R. Brad Jones · 2021 to 2026
$32.9M
Delaney AIDS Research Enterprise to Cure HIVUM1AI164560 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS, Sharon Ruth Lewin · 2021 to 2026
$32.0M
Patient and Population Health Outcomes Research SWGP30AI124414 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Kathryn M. Anastos · 2017 to 2026
$28.3M
Delaney AIDS Research Enterprise to Cure HIVUM1AI126611 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT, PICKER, LOUIS J. · 2016 to 2020
$27.9M
Optimization of Fc effector activity of anti-HIV antibodies to target HIV reservoirR01AI129795 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C, RAVETCH, JEFFREY VICTOR · 2017 to 2021
$4.2M
Mathematical modeling of optimal therapeutic combinations for HIV cureR01AI150500 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SCHIFFER, JOSHUA TISDELL · 2020 to 2024
$2.3M
Characterizing the virologic and immunologic signatures of HIV exceptional controlK23AI157875 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PELUSO, MICHAEL JOSEPH · 2021 to 2025
$927k
Simulating persistence and elimination of the HIV reservoirK25AI155224 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI REEVES, DANIEL · 2020 to 2024
$581k
NCATS NIH HHS UL1 TR001866NIAID NIH HHS K23 AI157875NIAID NIH HHS K25 AI155224NIAID NIH HHS L30 AI147159NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI124414NIAID NIH HHS R01 AI129795NIAID NIH HHS R01 AI150500NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI126611NIAID NIH HHS UM1 AI144462NIAID NIH HHS UM1 AI164560NIAID NIH HHS UM1 AI164565
6 · The paper itself

Abstract

Most proviruses persisting in people living with HIV (PWH) on antiretroviral therapy (ART) are defective. However, rarer intact proviruses almost always reinitiate viral rebound if ART stops. Therefore, assessing therapies to prevent viral rebound hinges on specifically quantifying intact proviruses. We evaluated the same samples from 10 male PWH on ART using the two-probe intact proviral DNA assay (IPDA) and near full length (nfl) Q4PCR. Both assays admitted similar ratios of intact to total HIV DNA, but IPDA found ~40-fold more intact proviruses. Neither assay suggested defective proviruses decay over 10 years. However, the mean intact half-lives were different: 108 months for IPDA and 65 months for Q4PCR. To reconcile this difference, we modeled additional longitudinal IPDA data and showed that decelerating intact decay could arise from very long-lived intact proviruses and/or misclassified defective proviruses: slowly decaying defective proviruses that are intact in IPDA probe locations (estimated up to 5%, in agreement with sequence library based predictions). The model also demonstrates how misclassification can lead to underestimated efficacy of therapies that exclusively reduce intact proviruses. We conclude that sensitive multi-probe assays combined with specific nfl-verified assays would be optimal to document absolute and changing levels of intact HIV proviruses.

Indexed as

HIV-1HIV InfectionsCD4-Positive T-LymphocytesDNA, ViralHumansMaleProvirusesViral LoadDNA, Viral

Identifiers

PMID37443365
PMCPMC10345136

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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.