COMPARATIVE EFFECTIVENESS OF LEVONORGESTREL (LNG) IMPLANT AND DEPOT MEDROXYPROGESTERONE ACETATE (DMPA) INJECTABLE FOR PREGNANCY PREVENTION AMONG WOMEN LIVING WITH HIV ON EFAVIRENZ OR DOLUTEGRAVIR

In sub-Saharan Africa, and specifically Malawi, numerous women of reproductive age are living with HIV (WLHIV) on life-long antiretroviral treatment (ART). Effective family-planning (FP) methods prevent unintended pregnancy, and thus can reduce vertical HIV transmission and maternal mortality. However, drug-drug interactions exist between certain hormonal contraceptives and ART. This dissertation compares the effectiveness of two leading, reversible contraceptive methods in Malawi— the levonorgestrel (LNG) implant and depot medroxyprogesterone acetate (DMPA) injectable—for WLHIV on efavirenz (EFV) or dolutegravir (DTG)-containing ART. We analyzed a prospective cohort study that enrolled 1,359 WLHIV on ART who recently initiated either LNG implant or DMPA injectable. Incident pregnancies were measured by urine pregnancy testing and pregnancy diagnosis at study visits conducted every 24 weeks over 96 to 192 weeks of follow-up. Marginal structural models were applied to evaluate comparative effectiveness of LNG implant vs. DMPA injectable. Among WLHIV using EFV-based ART, estimated pregnancy incidence rates were 6.6/100 PY (95% CI: 5.0, 8.7) in the LNG implant group and 7.3/100 PY (95% CI: 5.5, 9.7) in the DMPA group (incidence rate difference [IRD]: -0.7/100 PY, 95% CI: -3.5 to 2.0), based on the contraception initiated at study enrollment and median follow-up of 1.1 years. Results were similar when restricted to the first incident pregnancy during continued, typical use of the enrollment contraceptive method (pregnancy incidence rates: 5.7/100 PY for both LNG implant and DMPA injectable, IRD: 0.0 (95% CI: -2.6, 2.7)). Under continued DTG-based ART use among the full FP-ART cohort, we estimated the 192-week probability of incident pregnancy was 2.6% with LNG implant and 16.1% with DMPA injectable, each under continued and typical contraceptive method use (probability difference: -13.5%, 95% CI: -20.1%, -7.5%). The LNG implant had effectiveness similar to provider-administrated DMPA injectable for WLHIV using EFV-based ART. In contrast, the LNG implant was highly effective for WLHIV on DTG-based ART, with substantially better typical-use effectiveness than DMPA. For WLHIV, their ART regimen is a key consideration when selecting a new contraceptive method. Providers should carefully counsel their clients on the effectiveness, efficacy, safety risks, and potential drug-drug interactions of each contraceptive method option.