ArticleViruses2022
Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV.
Ashley F George, Matthew McGregor, David Gingrich, Jason Neidleman, Rebecca S Marquez, Kyrlia C Young, Kaavya L Thanigaivelan, Warner C Greene, Phyllis C Tien, Amelia N Deitchman and 2 more
Open access · goldAbstract read
In one paragraphArticle in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 57% of its field
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 registryThe 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 literatureWho cites it
0 citing papers in PubMed, 1 citations in OpenAlex.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
12 authors at 4 institutions in 1 country.
Ashley F GeorgeGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-1482-5244 Matthew McGregorGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-1547-5063 David GingrichDrug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA.
Jason NeidlemanGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.
Rebecca S MarquezWomen's Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USA.
Kyrlia C YoungGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.
Kaavya L ThanigaivelanGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.
Warner C GreeneGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-9896-8615 Phyllis C TienDepartments of Medicine and Veterans Affairs, University of California at San Francisco, San Francisco, CA 94143, USA.
Amelia N DeitchmanDrug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA.
Trimble L SpitzerLieutenant Colonel, United States Air Force, Medical Center, Women's Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USA.
Nadia R RoanGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-5464-1976 Gladstone Institutes · USNaval Medical Center Portsmouth · USUniversity of California, San Francisco · USSan Francisco VA Medical Center · US
Funding
HOPE - HIV Obstruction by Programmed EpigeneticsUM1AI164559 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Lishomwa C Ndhlovu, Melanie Maria Ott · 2021 to 2026
$32.2MCollaboratory of AIDS Researchers for Eradication (CARE)UM1AI164567 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2021 to 2026
$31.6MMOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0MElucidating the mechanism of progesterone-induced permissivity in the upperfemale reproductive tractR01AI127219 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROAN, NADIA R · 2016 to 2020
$2.1MEffects of PrEP Drugs on Female Genital HIV Infection and Women's Reproductive HealthK99HD110319 · NICHD · J. DAVID GLADSTONE INSTITUTES · PI GEORGE, ASHLEY F · 2022 to 2023
$253kNIAID NIH HHS R01 AI127219NIAID NIH HHS T32 AI007334NIAID NIH HHS UM1 AI164559NIAID NIH HHS UM1 AI164567NICHD NIH HHS K99 HD110319NIH HHS R01 AI127219NIH HHS UM1 AI164559
6 · The paper itselfAbstract
The efficacy of HIV pre-exposure prophylaxis (PrEP) is high in men who have sex with men, but much more variable in women, in a manner largely attributed to low adherence. This reduced efficacy, however, could also reflect biological factors. Transmission to women is typically via the female reproductive tract (FRT), and vaginal dysbiosis, genital inflammation, and other factors specific to the FRT mucosa can all increase transmission risk. We have demonstrated that mucosal fibroblasts from the lower and upper FRT can markedly enhance HIV infection of CD4+ T cells. Given the current testing of tenofovir disoproxil fumarate, cabotegravir, and dapivirine regimens as candidate PrEP agents for women, we set out to determine using in vitro assays whether endometrial stromal fibroblasts (eSF) isolated from the FRT can affect the anti-HIV activity of these PrEP drugs. We found that PrEP drugs exhibit significantly reduced antiviral efficacy in the presence of eSFs, not because of decreased PrEP drug availability, but rather of eSF-mediated enhancement of HIV infection. These findings suggest that drug combinations that target both the virus and infection-promoting factors in the FRT-such as mucosal fibroblasts-may be more effective than PrEP alone at preventing sexual transmission of HIV to women.
Indexed as
Anti-HIV AgentsHIV InfectionsSexual and Gender MinoritiesFemaleFibroblastsHomosexuality, MaleHumansMaleVaginaAnti-HIV Agentsfemale reproductive tractfibroblastsHIV transmissionpre-exposure prophylaxis
Identifiers
PMID36016345
PMCPMC9413545
OpenAlexW4289860877
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390