BACKGROUND: Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown.
METHODS: Fifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography-mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups.
RESULTS: 3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues.
CONCLUSIONS: We found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis.
CLINICAL TRIALS REGISTRATION: NCT03377608.
|Original language||English (US)|
|Number of pages||8|
|Journal||Clinical Infectious Diseases|
|State||Published - Apr 15 2020|
Bibliographical notePublisher Copyright:
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
- Lamivudine/analogs & derivatives
- Anti-HIV Agents/therapeutic use
- Medroxyprogesterone Acetate/therapeutic use
- Emtricitabine/therapeutic use
- HIV Infections/drug therapy
- Pre-Exposure Prophylaxis
- Adenine/analogs & derivatives
- Cytidine Triphosphate/analogs & derivatives
- Tenofovir/therapeutic use
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural