A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Antiretroviral Therapy

HIV Clinical Trial

Official title: A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-Infected Ugandan Women

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Contraception
• HIV

• NCT number: NCT02082652
• Study type: Interventional
• Source: University of Pittsburgh
• Status: Completed
• Phase: Phase 4
• Start date: October 2014
• Completion date: March 2016