Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV
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 reprodu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/8/1723 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ashley F. George |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:48:24Z |
| format | Article |
| id | doaj.art-f55403f065a443fe8877ab39b32d77fa |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T09:48:24Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f55403f065a443fe8877ab39b32d77fa2023-12-02T00:26:35ZengMDPI AGViruses1999-49152022-08-01148172310.3390/v14081723Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIVAshley F. George0Matthew McGregor1David Gingrich2Jason Neidleman3Rebecca S. Marquez4Kyrlia C. Young5Kaavya L. Thanigaivelan6Warner C. Greene7Phyllis C. Tien8Amelia N. Deitchman9Trimble L. Spitzer10Nadia R. Roan11Gladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USADrug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USAWomen’s Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USADepartments of Medicine and Veterans Affairs, University of California at San Francisco, San Francisco, CA 94143, USADrug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USALieutenant Colonel, United States Air Force, Medical Center, Women’s Health Clinic, Naval Medical Center, Portsmouth, VA 23708, USAGladstone Institute of Virology, University of California at San Francisco, San Francisco, CA 94158, USAThe 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.https://www.mdpi.com/1999-4915/14/8/1723HIV transmissionfemale reproductive tractpre-exposure prophylaxisfibroblasts |
| spellingShingle | 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 Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV Viruses HIV transmission female reproductive tract pre-exposure prophylaxis fibroblasts |
| title | Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV |
| title_full | Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV |
| title_fullStr | Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV |
| title_full_unstemmed | Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV |
| title_short | Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV |
| title_sort | female genital fibroblasts diminish the in vitro efficacy of prep against hiv |
| topic | HIV transmission female reproductive tract pre-exposure prophylaxis fibroblasts |
| url | https://www.mdpi.com/1999-4915/14/8/1723 |
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