Investigating interactions between efavirenz-based antiretroviral therapy and contraceptive implants

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 DESCRIPTION (provided by applicant): The overall goal of the proposed mentored career development award is to support Dr. Rena Patel's research training to develop as an independent, mixed methods researcher in HIV and women's health. Dr. Patel is currently an infectious diseases fellow at the University of California, San Francisco. Conducting the proposed studies in this application will facilitate her training goals of gaining a background in pharmacology, advancing her skills in epidemiology/biostatistics and qualitative research methods, and formalizing her experiences in implementation sciences. The proposal builds on the unique skills that she already has in the social sciences, qualitative research, and epidemiology while leveraging UCSF's world-class mentors, researchers, and facilities to ensure her success in becoming an independent investigator. The research objective of this proposal is to determine if interactions between efavirenz and contraceptive implants lead to contraceptive failures (i.e. unintended pregnancies). Unintended pregnancies among HIV-positive women impact HIV and maternal morbidity and vertical transmission of HIV. Optimizing contraception to avoid unintended pregnancies is imperative. Some pharmacokinetic data regarding drug-drug interactions between efavirenz and hormonal contraception have raised concerns for increased contraceptive failures. However, critical gaps exist in the literature and current HIV treatment guidelines with regard to concomitant use of efavirenz-based antiretroviral therapy (ART), now recommended as first-line ART in resource-limited settings, and contraceptive implants. In order to address the issue of potential interactions between efavirenz and implants comprehensively, we aim to conduct three distinct studies in western Kenya. For Aim 1, we will determine if implant etonogestrel concentrations decrease following initiation of efavirenz-based ART. For Aim 2, we will compare contraceptive failure or pregnancy rates among women using implants on efavirenz- vs. non-efavirenz based ART in a large clinic-based Kenyan cohort. Lastly, for Aim 3, we will determine how HIV-positive women, their partners, and providers reach decisions regarding concomitant ART and contraception initiation and choices, how potential data on interactions between ART and contraception would influence their choices, and to assess acceptability of alternative ART and/or contraceptive strategies. We hypothesize that implant etonogestrel concentrations will decrease following efavirenz-based ART initiation and pregnancy rates will be higher in implant users on efavirenz vs. non-efavirenz-based ART. The above aims will be among the first to comprehensively address the questions surrounding interactions between efavirenz-based ART and implants, and by the completion of this award, Dr. Patel will be in an excellent position to submit an R01 that furthers the research agenda in HIV and reproductive health.