Evidence map›Paper›PMID 40961226›Full record

Observational studyScience translational medicine2025

Sex differences in HIV-1 reservoir cell selection are linked to altered innate immune profiles.

Toong Seng Tan, Ce Gao, Alexander S Hochroth, Liliana Vela, Leah Carrere, Sruthi Kalavacherla, Seohyun Hong, Melanie Lancien, Chloe M Naasz, Aischa Niesar and 18 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. The HIV reservoir landscape in elite controllers.Current opinion in HIV and AIDS · 2026
    Review
  9. Review
  10. Article
  11. Review
  12. Review
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

28 authors.

Toong Seng TanRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-6751-5987
Ce GaoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-3775-790X
Alexander S HochrothRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-0394-2293
Liliana VelaRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0000-0445-7807
Leah CarrereRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0000-2481-5501
Sruthi KalavacherlaRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0004-4310-1511
Seohyun HongRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0004-3776-6330
Melanie LancienRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0003-3777-0271
Chloe M NaaszRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Aischa NiesarRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Samantha K MarziRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Isabelle C RosetoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0008-2976-0720
Benjamin BoneRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Xiaodong LianRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Yuko YukiBasic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.ORCID 0000-0003-1721-6003
Mathias ViardBasic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.ORCID 0000-0002-1737-8021
Rebecca HohDivision of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-5112-4220
Deborah K McMahonUniversity of Pittsburgh, Pittsburgh, PA 15260, USA.ORCID 0000-0002-4374-3539
Ronald J BoschCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Seble G KassayeDepartment of Medicine, Georgetown University Medical Center, Washington, DC 20057, USA.ORCID 0000-0002-7527-7384
Rajesh T GandhiInfectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA.
Mary CarringtonRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-2692-2180
Steven G DeeksDivision of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-6371-747X
Phyllis C TienDepartment of Medicine, University of California San Francisco and Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Michael J PelusoDivision of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-0585-6230
Jeffrey M JacobsonSchool of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.ORCID 0000-0003-0725-249X
Mathias LichterfeldRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0001-9865-8350
Xu G YuRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-8295-884X

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Maternal Morbidity and Mortality: Risk Factors, Early Detection and Personalized InterventionUL1TR001409 · NCATS · GEORGETOWN UNIVERSITY · PI GONDRE-LEWIS, MARJORIE C, MELLMAN, THOMAS A · 2015 to 2024
$37.8M
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
BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination ImmunotherapyUM1AI164570 · NIAID · WISTAR INSTITUTE · PI Luis J Montaner, James L. Riley · 2021 to 2026
$34.7M
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
ERASE HIV: Enterprise for Research and Advancements to Stop and Eradicate HIVUM1AI164562 · NIAID · EMORY UNIVERSITY · PI Deanna A Kulpa, Mirko Paiardini · 2021 to 2026
$30.0M
Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studiesU01HL146205 · NHLBI · GEORGETOWN UNIVERSITY · PI SEBLE G KASSAYE, DANIEL J MERENSTEIN · 2019 to 2026
$23.5M
Gates Foundation INV-002703NCATS NIH HHS KL2 TR001432NCATS NIH HHS TL1 TR001431NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR001409NHLBI NIH HHS U01 HL146193NHLBI NIH HHS U01 HL146205NHLBI NIH HHS U01 HL146242NIAID NIH HHS K23 AI157875NIAID NIH HHS K24 AI155233NIAID NIH HHS R01 AI152979NIAID NIH HHS R01 AI176579NIAID NIH HHS R01 AI184094NIAID NIH HHS R21 AI189231NIAID NIH HHS R37 AI155171NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIAID NIH HHS UM1 AI164560NIAID NIH HHS UM1 AI164562NIAID NIH HHS UM1 AI164566NIAID NIH HHS UM1 AI164570NIDA NIH HHS R33 DA047034NIDA NIH HHS R61 DA047034NIMH NIH HHS R01 MH134823
6 · The paper itself

Abstract

HIV-1 persistence despite suppressive antiretroviral therapy (ART) is primarily because of infected memory CD4 T cells, so-called viral reservoir cells, that harbor chromosomally integrated viral DNA as a "provirus" and resist clearance by the human immune system. Biological sex affects host immune responses and may influence selection and evolution of HIV-1 reservoir cells during long-term ART for HIV infection. We assessed more than 4073 individual proviruses through single-molecule amplification from 30 females and 35 males living with HIV-1 and treated with ART for a median of 20 years. We observed that the HIV-1 reservoir profile in females was characterized by lower proviral phylogenetic complexity, an increased proportion of clonally expanded intact proviruses, and a higher proportion of intact proviruses integrated into repressive heterochromatin locations of the human genome. The evolution of this distinct viral reservoir profile in females was associated with an improved signature of innate immune responses, specifically those of NK cells. On the contrary, signs of viral sequence adaptation to adaptive T cell immune responses were more pronounced in intact HIV-1 proviruses from males. Collectively, these data suggest a stronger ability of the female immune system to drive immune selection of HIV-1 reservoir cells during ART, putatively because of improved innate immune function.

Indexed as

HIV-1HIV InfectionsImmunity, InnateProvirusesAdultAgedAged, 80 and overAnti-HIV AgentsCD4-Positive T-LymphocytesCross-Sectional StudiesDNA, ViralFemaleHumansKiller Cells, NaturalMaleMiddle AgedAnti-HIV AgentsDNA, Viral

Identifiers

PMID40961226
PMCPMC12590489

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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.