A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Antiretroviral Therapy
Condition: HIV; Contraception
Study type: Interventional
Phase: Phase 4

Summary: 
      Antiretroviral therapy (medicines used to treat HIV) can interact with hormonal
      contraceptives which might decrease their effectiveness. The single-rod etonogestrel
      contraceptive implant is being more commonly used in low- and middle-income countries because
      if the ease of insertion and removal. Efavirenz and nevirapine are first-line HIV medicines
      in Sub-Saharan Africa and this study will help determine an effective way to use these
      medicines with the etonogestrel implant. The investigators hypothesize that women receiving
      nevirapine- or efavirenz-based antiretroviral therapy will have lower etonogestrel levels in
      their blood after six months of insertion as compared to women not taking antiretroviral
      therapy.
    

Detailed description: 
      Modern contraceptive use by HIV-infected women not only prevents pregnancy-related
      complications and economic disparity, but also prevents perinatal HIV transmission. Despite
      the clear benefits of highly effective modern contraceptives, there are significant
      unanswered questions about their safety in women infected with HIV, particularly women who
      are on anti-retroviral therapy (ART). Currently, non-nucleoside reverse transcriptase
      inhibitors (NNRTIs), such as nevirapine (NVP) and efavirenz (EFV), are the most widely
      prescribed HIV medications in sub-Saharan Africa and recently the WHO recommended the
      EFV-based ART be recommended as first-line therapy for HIV-1 infected adults, including women
      of reproductive age. Contraceptive implants are becoming increasingly available and popular
      in sub-Saharan Africa, and the etonogestrel (ENG) implant is a single rod, making insertion
      and removal easier than other contraceptive implants. The clinical data on concurrent use of
      NNRTIs and the ENG implant are limited to six case reports of contraceptive failures in the
      setting of EFV-based ART, highlighting the potential for a clinically significant drug-drug
      interaction. The investigators aim to perform a pharmacokinetic (PK) study evaluating the
      interaction between the ENG implant and NNRTI-based ART. The investigators propose a
      non-randomized, open-label, parallel, three-group, sparse-sampling PK study to compare ENG PK
      parameters between a control group (no ART) and two treatment groups (EFV- or NVP-based ART)
      in 60 HIV-1 infected women, 20 women in each group. The primary endpoint is the comparison of
      the mean ENG concentrations at month 6 between the control group and NNRTI treatment groups.
      The investigators hypothesize that women in the EFV-based and NVP-based ART group will have a
      significantly lower mean ENG concentration 6 months post-implant insertion, as compared to
      women in the control group. The investigators also aim to: 1) predict the disposition of ENG
      in women on NNRTI-based ART over the subsequent 2.5 years of intended use through PK modeling
      of ENG concentrations beyond 6 months of use in HIV-infected women, 2) estimate the long-term
      impact of chronic ENG exposure on EFV or NVP concentrations measured before and during 6
      months of combined use, and 3) compare side-effect frequencies of the ENG subdermal implant
      in women not on ART and on concomitant NNRTI-based ART. The results will guide clinicians
      caring for HIV-infected women on whether using NNRTI-based therapy together with the ENG
      implant will jeopardize contraceptive efficacy due to a reduction in ENG exposure.
    

Intervention name(s): Etonogestrel
Intervention type(s): Drug
Intervention description(s): Etonogestrel single-rod subdermal implant (68mg/rod) is placed upon enrollment (day 0) and remains in place until participant requests removal or for the duration of active drug (currently approved for 3 years of use).
Other intervention name(s): Implanon; Nexplanon
Intervention MeSH terms: Etonogestrel
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Etonogestrel; Efavirenz; Nevirapine; Pharmacokinetics