Prospective Cohort Evaluating Pregnancy Rates, PK Interactions Among HIV+ Women on EFV Initiating LNG Implant or DMPA
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      The purpose of this study is to compare the pregnancy rates among women who are using the HIV
      drug Efavirenz and either the birth control injection or implant.
    

Detailed description: 
      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.

      The investigators plan to enroll 25 of the 710 EFV users from their prospective cohort in
      Objective 1 who are initiating the LNG implant into the pharmacokinetic sub-study. All 25 of
      these women will be enrolled from 1 health facility, Area 18 Health Centre, and all women
      will be taking EFV 400 mg daily, which is the standard dose that Malawi will be implementing
      this year due to its equivalent efficacy but decreased cost and side effects when compared to
      EFV 600 mg daily. Follow-up visits for women in the sub-study will be conducted at 4, 12, 24,
      36, and 48 weeks post-implant initiation. Since these women would already be attending visits
      at 4, 24, and 48 weeks post-implant initiation, there will only be 2 extra study visits for
      these sub-study participants at 12 weeks post-implant initiation (Visit 1a) and 36 weeks
      post-implant initiation (Visit 2a). During the extra Visits 1a and 2a, urine, blood, and hair
      specimens will be obtained so that pregnancy testing can be performed and blood and hair can
      be stored for VL, EFV, and LNG testing.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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
      
Keywords: Pregnancy rates; pharmacokinetic interactions; Women on efavirenz; initiating the Levonorgestrel Implant; initiating the Depot Medroxyprogesterone Acetate Injectable