Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP Against HIV

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2022 Aug 26

PMID 36016345

Authors

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

Trimble L Spitzer

Nadia R Roan

Affiliations

Soon will be listed here.

Abstract

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.

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