A Prospective Cohort Evaluating the Pregnancy Rates and Pharmacokinetic Interactions Among HIV-infected Malawian Women on Efavirenz Initiating the Levonorgestrel Implant or the Depot Medroxyprogesterone Acetate Injectable

Objective 1: To compare the typical-use pregnancy rates of 710 HIV+ DMPA-users on EFV with 710 HIV+ LNG implant users on EFV through a prospective observational cohort.

The investigators will enroll 710 HIV-infected women on EFV who are initiating the LNG implant and 710 HIV-infected women on EFV who are initiating the DMPA injectable and follow them 1 month after contraceptive initiation and then every 6 months until the end of the 4-year study time period. The investigators will recruit and enroll over a period of 2 years; those who are enrolled at the beginning of the enrollment period may complete up to 4 years of follow-up, whereas those who are enrolled at the end of the 2-year enrollment period will complete 2 years of follow-up. Women will have urine, blood, and hair specimens obtained at each study visit. The primary outcome will be incident pregnancy, evaluated by urine pregnancy testing. The secondary outcome will be contraceptive continuation, evaluated by palpation (for LNG implant) and review of the woman's medical record and study forms (for DMPA). A marginal structural Poisson model will be used to estimate the effect of implant compared to DMPA upon pregnancy incidence. The investigators will adjust for key potential confounders, including frequency of intercourse, age, and body mass index (BMI).

Objective 2: To assess whether greater EFV exposure (measured by hair concentrations) is associated with contraceptive failure in LNG implant users in a 2:1 nested case-control study of 240 LNG implant users.

The investigators estimate that a maximum of 120 pregnancies will occur among LNG implant users in the cohort in Objective 1. From this cohort, the investigators will compare 80 pregnant women who were using the LNG implant at the time of conception and 160 controls who had intercourse during the previous 3 months and were not pregnant after a similar period of LNG implant use. A conditional logistic regression model will be used to assess the association between EFV hair concentrations and contraceptive failure; key potential confounders the investigators will adjust for in the analysis include frequency of intercourse, age, weight, and length of time on EFV. The data for this Objective's exposure, outcome, and confounders will be derived from the Data Collection Forms and study specimens obtained in Objective 1.

Objective 3: To evaluate the effect of EFV 400 mg daily on LNG concentrations among a subset of 25 women enrolled in the prospective cohort study who initiated the LNG implant.