{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:58:03Z","timestamp":1760230683962,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["R01 AI127219","UM1 AI164559"],"award-info":[{"award-number":["R01 AI127219","UM1 AI164559"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH HOPE Collaboratory","doi-asserted-by":"publisher","award":["R01 AI127219","UM1 AI164559"],"award-info":[{"award-number":["R01 AI127219","UM1 AI164559"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of California at San Francisco (UCSF) AIDS Research Institute Strategic Support Award","award":["R01 AI127219","UM1 AI164559"],"award-info":[{"award-number":["R01 AI127219","UM1 AI164559"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2014such as mucosal fibroblasts\u2014may be more effective than PrEP alone at preventing sexual transmission of HIV to women.<\/jats:p>","DOI":"10.3390\/v14081723","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T02:12:39Z","timestamp":1659665559000},"page":"1723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-5244","authenticated-orcid":false,"given":"Ashley F.","family":"George","sequence":"first","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-5063","authenticated-orcid":false,"given":"Matthew","family":"McGregor","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gingrich","sequence":"additional","affiliation":[{"name":"Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Neidleman","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca S.","family":"Marquez","sequence":"additional","affiliation":[{"name":"Women\u2019s Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyrlia C.","family":"Young","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaavya L.","family":"Thanigaivelan","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9896-8615","authenticated-orcid":false,"given":"Warner C.","family":"Greene","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Departments of Medicine and Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyllis C.","family":"Tien","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Veterans Affairs, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-463X","authenticated-orcid":false,"given":"Amelia N.","family":"Deitchman","sequence":"additional","affiliation":[{"name":"Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trimble L.","family":"Spitzer","sequence":"additional","affiliation":[{"name":"Lieutenant Colonel, United States Air Force, Medical Center, Women\u2019s Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5464-1976","authenticated-orcid":false,"given":"Nadia R.","family":"Roan","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"ref_1","unstructured":"(2022, July 21). 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