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

• Published in: Viruses Vol. 14; no. 8; p. 1723
• Main Authors: George, Ashley F, McGregor, Matthew, Gingrich, David, Neidleman, Jason, Marquez, Rebecca S, Young, Kyrlia C, Thanigaivelan, Kaavya L, Greene, Warner C, Tien, Phyllis C, Deitchman, Amelia N, Spitzer, Trimble L, Roan, Nadia R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2022; MDPI
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiviral activity; Antiviral agents; CD4 antigen; Disease transmission; Drug dosages; Dysbacteriosis; Endometrium; Female; female reproductive tract; Fibroblasts; Flow cytometry; Health aspects; HIV; HIV infection; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV transmission; Homosexuality, Male; Human immunodeficiency virus; Humans; Infections; Lymphocytes; Lymphocytes T; Male; Mucosa; pre-exposure prophylaxis; Prevention; Prophylaxis; Reproductive organs, Female; Reproductive system; Sexual and Gender Minorities; Tenofovir; Vagina; Viruses; Women; United States; United States > US; fibroblasts; pre-exposure prophylaxis; HIV transmission; female reproductive tract
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14081723

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.