Effect of Dolutegravir on Etonogestrel Levels in HIV-infected Women in Botswana
Condition: Contraceptive Usage; HIV Infections; Drug Interaction
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      The primary aim is to assess if etonogestrel (ENG) implant users taking dolutegravir (DTG)
      have a 20% or greater change in their ENG plasma levels, compared to women taking no
      antiretroviral therapy (ART). A secondary aim is to assess whether ENG implant users taking
      dolutegravir have significantly higher ENG plasma levels than ENG implant users taking
      efavirenz.

      This is a cross-sectional, non-randomized evaluation to compare ENG levels between 3 and 12
      months post-implant insertion in three groups of women: 1) women using DTG-based ART (n=90),
      2) women using EFV-based ART (n=90), and 3) women using no ART (not HIV infected) (n=90).
      This study will be conducted in Botswana in Southern Africa among women using the ENG
      implant, and involves a one-time collection of blood and questionnaire.
    

Detailed description: 
      Efavirenz-based antiretroviral therapy is effective in treating HIV and had become standard
      in the World Health Organization (WHO) guidelines. However, despite its effectiveness in
      lowering viral load, there is also solid evidence that it decreases the effectiveness of
      etonogestrel-releasing implants. This presents a difficult clinical scenario in countries
      where the HIV burden is significant in reproductive age women.

      Following the SINGLE trial, dolutegravir has replaced efavirenz in many settings as
      first-line ART. In 2016, Botswana became the first country in Africa to adopt this as a
      guideline, however, the effect that dolutegravir has on hormonal contraceptives has not been
      widely studied. This project seeks to understand the interaction between etonogestrel levels
      in HIV-infected women who are using dolutegravir-based ART by directly measuring etonogestrel
      blood levels using liquid chromatography-mass spectrometry in HIV-negative and HIV-infected
      women using contraceptive implants.

      Because the implant is fairly new in Botswana, most participants will have had implants
      inserted 3-12 months prior to study. An HIV-infected, non-ART, comparison group is no longer
      permissible, practically or ethically, as countries across Africa, including Botswana, are
      moving to HIV "Test and Treat." This means that ART initiation is now occurring at time of
      HIV-diagnosis regardless of cluster of differentiation 4 (CD4) count or disease stage;
      therefore, in this study, the comparison group will be HIV-uninfected implant users. This
      comparison will answer the key question of whether the ENG implant when used simultaneously
      with DTG provides plasma ENG levels comparable to a group in which it has established
      contraceptive efficacy (i.e. HIV-uninfected, healthy women of reproductive age).
    

Intervention name(s): dolutegravir; ENG implant; Efavirenz
Intervention type(s): Drug; Device; Drug
Intervention description(s): HIV integrase strand transfer inhibitor used in combination ART; Reversible contraception implant; non-nucleoside reverse transcriptase inhibitor used in combination ART
Other intervention name(s): Tivicay; DTG; Nexplanon ®; Implanon NXT ®; single-rod, etonogestrel-releasing, subdermal implant; Sustiva; EFV
Intervention MeSH terms: Efavirenz; Dolutegravir; Etonogestrel
Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Reproductive-aged HIV-infected women using dolutegravir and using single-rod,
        etonogestrel-releasing subdermal implant.

        Reproductive-aged HIV-infected women using efavirenz and using single-rod,
        etonogestrel-releasing subdermal implant.

        Reproductive-aged HIV-unifected women using single-rod, etonogestrel-releasing subdermal
        implant.
      
Biospecimen description: 
      plasma
    
Keywords: DTG; Dolutegravir; Efavirenz; Etonogestrel