Darunavir and rilpivirine steady state trough plasma concentrations with and without progestin contraceptive implant and HIV virologic outcomes among Ugandan women living with HIV.

Abstract

Background Through sustained viral suppression and prevention of unintended pregnancies, effective antiretroviral drugs like rilpivirine (RPV) and darunavir (DRV), and contraceptives like the progestin implant, can significantly improve the overall health of women living with HIV (WLHIV). Rilpivirine and darunavir have been shown to have no clinically significant effect on the concentration of the etonogestrel (ENG) and levonorgestrel (LNG) contraceptive. However, no studies have evaluated the effect of progestin implant contraceptives on the concentrations of rilpivirine and darunavir. Objective To describe the effect of progestin implant contraceptive use on the trough plasma concentrations of darunavir and rilpivirine and HIV treatment outcomes among WLHIV attending the Infectious Diseases Clinic. Patients and methods This sub-study was a two-group pre-test post-test Quasi experimental study in which we reviewed secondary data from two clinical trials (the DRIVE studies) of adult females receiving care at an urban HIV specialized centre. The DRIVE studies were aimed at characterising the pharmacokinetics (PK) of ENG and LNG among WLHIV receiving either rilpivirine or darunavir based antiretroviral therapy (ART). Participants were switched to rilpivirine-based ART with a run-in period of six-weeks or darunavir-based ART with a run-in period of two weeks prior to implant insertion. Plasma was collected on day 0, and 4, 12, 24 36, and 48-weeks post implant-insertion. Rilpivirine and darunavir plasma trough samples were collected between 20 -28hours and 10-14 hours post dose respectively. Data on day 0 and week 24 rilpivirine and darunavir plasma trough concentrations were analysed for this study. Rilpivirine and darunavir plasma trough concentrations were summarized descriptively (median and inter-quartile range). Within group pre (day 0) and post- implant insertion (week 24) darunavir and rilpivirine plasma trough concentrations were compared using geometric mean ratios (GMR) and 90% confidence interval (CI). Data on virologic failure at week 24 were reported using frequencies and proportions. Results A total of 58 and 57 participants were included in the rilpivirine and darunavir groups respectively. Average age was 35 years and 38 years for the rilpivirine and darunavir group respectively. Day 0 and week 24 rilpivirine and darunavir plasma trough concentrations were similar [rilpivirine: 1.12 (0.88, 1.43); darunavir: 1.11 (0.79, 1.58)]. Concentrations remained similar when the data were stratified by type of progestin [rilpivirine and etonogestrel: 1.24 (0.88, 1.77); rilpivirine and levonorgestrel: 1.02 (0.72, 1.44); darunavir and etonogestrel: 1.04 (0.64, 1.69); darunavir and levonorgestrel: 1.20 (0.74, 1.96)]. All study participants (100%) had a viral load of less than 200copies/mL at weeks 12 and 24. Conclusion Over 24 weeks of combined use, progestin implant contraceptive use did not significantly change the steady state trough plasma concentrations of either rilpivirine or darunavir. Concomitant use of progestin implant contraceptives and rilpivirine or darunavir based ART resulted in sustained virologic suppression after 24 weeks of follow up. Rilpivirine and darunavir based ART could be considered for WLHIV who desire a progestin contraceptive implant as the preferred method of contraception.