The effect of dolutegravir-based ART on serum etonogestrel levels in HIV-infected women using contraceptive implants in Botswana
Awarded 2016
Trainee Grants
Serena Liu, BS
Columbia University

The etonogestrel (ENG) implant is the most effective contraceptive method available. However, its use is complicated in high-HIV prevalence settings: data show reduced implant contraceptive efficacy during efavirenz-based antiretroviral therapy (ART), the first-line ART in resource-poor areas, due to drug-drug interactions. New, more effective strategies for concomitant ART-implant use need to be identified. Dolutegravir-based ART, first-line in many resource-rich countries, is being introduced in Africa. Dolutegravir will become more available in the future, replacing efavirenz-based ART, which has been found to reduce ENG levels by 70%. No data exist regarding the pharmacokinetic effects of dolutegravir-based ART on the ENG implant. Botswana, where more than 30% of women of reproductive age are HIV-infected, is the first African country to introduce dolutegravir. In the proposed pharmacokinetic study, we aim to understand if concomitant use of dolutegravir-ART threatens the implant’s contraceptive efficacy. This study will take place in Gaborone, Botswana and compare serum ENG levels in two groups of women with an ENG implant: women using dolutegravir-based ART versus women using no ART. With 30 women per group, we will have statistical power to detect 20% or greater decrease in ENG levels in the dolutegravir group compared to no treatment. This study will evaluate whether the dolutegravir- implant combination avoids drug-drug interactions that lead to unintended pregnancies with efavirenz. This question is of clinical importance for the whole of Africa as dolutegravir use is expanded, and the answer will enable the development of evidence-based guidance to optimize contraceptive care for HIV-infected women.