Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding, or, in the case of pre-exposure prophylaxis, HIV prevention. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. However, despite widespread lamivudine use, lamivudine triphosphate (3TC-TP) exposure in FGT is unknown. Furthermore, to facilitate development of multipurpose prevention for contraception and HIV, a better understanding of exogenous hormone effect on FGT antiretroviral exposure is needed.
HIV-positive, virologically suppressed, non-pregnant women, receiving combination TDF/3TC as part of antiretroviral therapy, were recruited in Kampala, Uganda. Women receiving depot-medroxyprogesterone (DMPA group) or using non-hormonal contraception (non-HC group) participated in a single visit study . Cervical biopsies were obtained for quantification of TFV-DP, 3TC-TP, and endogenous dATP and dCTP using liquid chromatography with tandem mass spectrometry. Blood plasma was collected to assess medication adherence. Differences between groups were tested using multiple linear regression on log-transformed data and adjusted for age, weight, and plasma drug concentrations (for tissue) or time since last dose (for plasma).
Fifty women aged 21-34 years were enrolled between Nov 2017 and March 2018. One subject in the DMPA group and two in the non-HC group were excluded from antiretroviral quantification as plasma concentrations were indicative of non-adherence. One additional biopsy in DMPA group was excluded due to sample processing error. Unadjusted medians (25th, 75th percentile) are reported in attached table. Concentrations of 3TC-TP were significantly higher than TFV-DP in cervical tissues with a geometric mean ratio of 17.3. Cervical TFV-DP was 64% higher in DMPA users compared to non-HC users (p=0.02). No differences were found between groups for TFV or 3TC in plasma, or in 3TC-TP, dATP, dCTP in cervical tissues.
These data provide the first information on drug exposure of 3TC-TP in the FGT following oral dosing. Similar to reports of FTC-TP, 3TC-TP was significantly higher than TFV-DP in cervical tissue, suggesting it may be an option for prophylaxis. TFV-DP was significantly higher in DMPA users compared to women using non-hormonal contraception, suggesting prevention efficacy is unlikely to be compromised by injectable progestin contraceptive use.