Evidence map›Paper›PMID 40987290›Full record

ArticleCell systems2025

Mild HIV-specific selective forces overlaying natural CD4+ T cell dynamics explain the clonality and decay dynamics of HIV reservoir cells.

Daniel B Reeves, Danielle N Rigau, Arianna Romero, Hao Zhang, Francesco R Simonetti, Joseph Varriale, Rebecca Hoh, Li Zhang, Kellie N Smith, Luis J Montaner and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Daniel B ReevesVaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA 98144, USA; Department of Global Health, University of Washington, Seattle, WA 98144, USA. Electronic address: dreeves@fredhutch.org.
Danielle N RigauSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Arianna RomeroSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Hao ZhangDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Francesco R SimonettiSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Joseph VarrialeSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Rebecca HohSchool of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Li ZhangBloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21205, USA.
Kellie N SmithBloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21205, USA.
Luis J MontanerThe Wistar Institute, Philadelphia, PA 19104, USA.
Leah H RubinSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Stephen J GangeSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Nadia R RoanSchool of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
Phyllis C TienSchool of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Joseph B MargolickDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Michael J PelusoSchool of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Steven G DeeksSchool of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Joshua T SchifferVaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA 98144, USA; Department of Medicine, University of Washington, Seattle, WA 98144, USA.
Janet D SilicianoSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Robert F SilicianoSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Baltimore, MD, USA.
Annukka A R AntarSchool of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: aantar1@jhmi.edu.

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI CONNIE L CELUM · 1988 to 2026
$104.9M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Anna Palmer Durbin · 2012 to 2026
$67.0M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
SF Bay Area MACS/WIHS Combined Cohort StudyU01HL146242 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Bradley E Aouizerat, Jennifer Cohen Price · 2019 to 2026
$36.3M
Sex differences in the role of multi-omicsin HIV-associated carotid artery atherosclerosisU01HL146193 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Stephen J Gange, Elizabeth Topper · 2019 to 2026
$35.8M
Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney CollaboratoryUM1AI164566 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Ann M Chahroudi, Deborah Persaud · 2021 to 2026
$35.5M
Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center - Admin Supplement: Vision and dual sensory loss in HIV-infected older adultsU01HL146201 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI TODD T BROWN, Joseph B. Margolick · 2019 to 2026
$33.7M
First-in-human study of two anti-SARS CoV-2 antibodies in health volunteersUM1AI126620 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J, RILEY, JAMES L. · 2016 to 2021
$24.5M
Kidney Transplantation from Donors with HIV: Impact on Rejection and Long-term OutcomesU01AI177211 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Christine Marie Durand, DORRY L. SEGEV · 2023 to 2026
$6.9M
Phylodynamic mechanisms of HIV reservoir seeding and maintenanceR01AI186721 · NIAID · FRED HUTCHINSON CANCER CENTER · PI Daniel Reeves · 2024 to 2026
$2.6M
Mathematical modeling of optimal therapeutic combinations for HIV cureR01AI150500 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SCHIFFER, JOSHUA TISDELL · 2020 to 2024
$2.3M
NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR003098NHLBI NIH HHS U01 HL146193NHLBI NIH HHS U01 HL146201NHLBI NIH HHS U01 HL146242NIAID NIH HHS K08 AI143391NIAID NIH HHS K23 AI157875NIAID NIH HHS K25 AI155224NIAID NIH HHS L30 AI126550NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI094189NIAID NIH HHS R01 AI150500NIAID NIH HHS R01 AI186721NIAID NIH HHS R21 AI186783NIAID NIH HHS U01 AI177211NIAID NIH HHS UM1 AI126620NIAID NIH HHS UM1 AI164566NIH HHS DP5 OD031834
6 · The paper itself

Abstract

To determine whether HIV persistence arises from the natural dynamics of memory (m)CD4+ T cells, we compare clonal dynamics of HIV proviruses and mCD4+ T cells from the same people living with HIV (PWH) on antiretroviral therapy and from matched HIV-seronegative people (N = 51). HIV proviruses are more clonal than mCD4+ T cells but similarly clonal to antigen-specific cells. Increasing reservoir clonality over time and differential decay of intact and defective proviruses are not explained by mCD4+ T cell kinetics alone. We develop and validate a stochastic model trained on 10 quantitative data metrics, which shows that negative selection against HIV-infected cells is necessary to explain all metrics. We estimate the strength of negative selection, finding that death of cells harboring intact and defective proviruses is infrequently (∼6% and ∼2% on average) due to HIV-specific factors. Thus, our data indicate that HIV persistence is mostly, but not entirely, driven by natural mCD4+ kinetics.

Indexed as

CD4-Positive T-LymphocytesHIV-1HIV InfectionsFemaleHumansMaleProvirusesViral Loadantigen-specificCD4+ T cellsclonalecologyHIV cureHIV reservoirlatent reservoirmathematical modelingreservoir decayTCR

Identifiers

PMID40987290
PMCPMC12694735

What OpenQuestion holds

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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.