Evidence map›Paper›PMID 38956017›Full record

ArticleNature communications2024

HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy.

Guinevere Q Lee, Pragya Khadka, Sarah N Gowanlock, Dennis C Copertino, Maggie C Duncan, F Harrison Omondi, Natalie N Kinloch, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

21 authors.

Guinevere Q LeeDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA. gul4001@med.cornell.edu.ORCID 0000-0002-9412-886X
Pragya KhadkaDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
Sarah N GowanlockDepartment of Microbiology and Immunology, Western University, London, ON, Canada.
Dennis C CopertinoDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0002-3217-4713
Maggie C DuncanFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
F Harrison OmondiFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.ORCID 0000-0003-0940-7512
Natalie N KinlochFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Jingo KasuleRakai Health Sciences Program, Kalisizo, Uganda.
Taddeo KityamuweesiRakai Health Sciences Program, Kalisizo, Uganda.
Paul BuuleRakai Health Sciences Program, Kalisizo, Uganda.
Samiri JamiruRakai Health Sciences Program, Kalisizo, Uganda.
Stephen TomusangeRakai Health Sciences Program, Kalisizo, Uganda.
Aggrey AnokRakai Health Sciences Program, Kalisizo, Uganda.
Zhengming ChenDepartment of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine, New York, NY, USA.
R Brad JonesDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0003-4470-1231
Ronald M GaliwangoRakai Health Sciences Program, Kalisizo, Uganda.
Steven J ReynoldsRakai Health Sciences Program, Kalisizo, Uganda.
Thomas C QuinnDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Zabrina L BrummeFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.ORCID 0000-0002-8157-1037
Andrew D Redd *Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jessica L Prodger *Department of Microbiology and Immunology, Western University, London, ON, Canada.

Funding

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
International Center for Excellence in Research (ICER) in Uganda: Impact of ARVsZIAAI001040 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI REYNOLDS, STEVEN · 2009 to 2025
$23.5M
International Studies of the Acquired Immune Deficiency Syndrome (AIDS)ZIAAI000361 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI REDD, ANDREW · 2009 to 2025
$15.8M
Characterization of Non-subtype B HIV-1 Reservoirs and its Association with Longitudinal Clinical OutcomesR01AI162221 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, GUINEVERE · 2021 to 2025
$2.1M
Insights into the dynamics of clonal expansion of genome-intact proviruses by examining longitudinal evolution of HIV proviral DNA compositionsR21AI150398 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, GUINEVERE · 2020 to 2021
$466k
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) NAGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) Canada Research Chairs ProgramGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) CGS-M awardsGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT-159625Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) Vanier Canada Graduate ScholarshipMichael Smith Foundation for Health Research (MSFHR) Scholar AwardNIAID NIH HHS R01 AI162221NIAID NIH HHS R21 AI150398NIAID NIH HHS UM1 AI164565U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI162221U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21AI150398U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) UM1AI164565Wellcome TrustWellcome Trust (Wellcome) 107752/Z/15/Z
6 · The paper itself

Abstract

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

Indexed as

CD4-Positive T-LymphocytesGenome, ViralHIV-1HIV InfectionsProvirusesAdultAnti-HIV AgentsDNA, ViralFemaleHumansMaleUgandaViral LoadAnti-HIV AgentsDNA, Viral

Identifiers

PMID38956017
PMCPMC11219899

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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.