Evidence map›Paper›PMID 40327405›Full record

ArticleJCI insight2025

Biological sex and age influence GS-9620 activity ex vivo.

Carissa S Holmberg, Callie Levinger, Adam R Ward, Alberto Bosque

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

4 authors.

Carissa S HolmbergDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Callie LevingerDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Adam R WardDivision of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.6.
Alberto BosqueDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.

Funding

SWG 2: Cure Research Scientific Working GroupP30AI117970 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI Italo Mocchetti · 2015 to 2026
$29.6M
Hormonal control of HIV latencyR01AI154518 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI BOSQUE, ALBERTO · 2020 to 2023
$1.6M
Training in HIV Persistence, Co-morbidities and TherapeuticsT32AI158105 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI BOSQUE, ALBERTO, MAGGIRWAR, SANJAY B. · 2021 to 2025
$909k
NIAID NIH HHS P30 AI117970NIAID NIH HHS R01 AI154518NIAID NIH HHS T32 AI158105
6 · The paper itself

Abstract

Toll-like receptors (TLRs) are being explored to enhance immunity in HIV cure strategies. The TLR7 agonist GS-9620 promotes immune activation, reactivates latent HIV, and delays viral rebound in some people with HIV. Previous work has shown that biological sex influences TLR7 signaling. This study examined the interplay between biological sex, age, and the sex hormones 17β-estradiol, progesterone, and testosterone on GS-9620's ability to promote cytokine secretion and activate CD4+ T, CD8+ T, and NK cells ex vivo. Interestingly, sex hormones had no effect on GS-9620-mediated immune activation or cytokine induction. However, we found that GS-9620 activity was influenced by age only in female donors. Further, we found that GS-9620-mediated CD4+ T cell activation was positively correlated with the induction of IFN-γ and IL-12, while CD4+ T cell activation and IL-12 production were negatively correlated with age. Additionally, CD8+ T cell activation was positively correlated with IFN-γ production. Mechanistically, IFN-γ was sufficient to promote higher immune activation of both CD4+ and CD8+ T cells in female versus male donors. In conclusion, biological sex and age, but not sex hormones, influence GS-9620-mediated immune activation. Understanding these factors will help in designing and evaluating future clinical trials using GS-9620 for an HIV cure.

Indexed as

HIV InfectionsToll-Like Receptor 7AdultAge FactorsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesEstradiolFemaleHumansInterferon-gammaKiller Cells, NaturalLymphocyte ActivationMaleMiddle AgedProgesteroneCytokinesEstradiolInterferon-gammaProgesteroneTestosteroneTLR7 protein, humanToll-Like Receptor 7AIDS/HIVInnate immunitySex hormonesTherapeutics

Identifiers

PMID40327405
PMCPMC12220944

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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.