A Pharmacokinetic Evaluation of Levonorgestrel Implant and Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-infected Ugandan Women

0022-14-EP

The use of hormone contraception poses a significant challenge for the estimated 16 million HIV-infected women of childbearing age. This is due to known drug interactions with antiretroviral therapy (medicines used to treat HIV) that may jeopardize contraception effectiveness. By evaluating the impact of antiretroviral therapy on a levonorgestrel subdermal implant, the most widely available hormone implant in low and middle-income countries, this study will translate its findings into an evidence-based approach to co-manage these important medications. The investigators hypothesize that women receiving nevirapine or efavirenz-based antiretroviral therapy will have a significant decrease in the mean levonorgestrel plasma concentration measured six months after the implant's insertion as compared to those women who are not taking antiretroviral therapy. Although the implant's efficacy may be retained initially, the investigators propose that a decrease in levonorgestrel concentrations in women receiving antiretroviral therapy may jeopardize the implant's effectiveness near the end of its intended duration of use (5 years).

2014-03-04

2014-09-01

2015-03-04

Completed

Early phase I

60

Inclusion Criteria: * Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Women age 18 years or older * Diagnosed with HIV-1 infection * Desiring LNG subdermal implant as a contraceptive method * Subjects not yet eligible for ART (based on the Ugandan Treatment Guidelines); or subjects receiving nevirapine or efavirenz-based ART for a minimum of 1 month prior to screening Exclusion Criteria: * For patients currently on ART: HIV-1 RNA \> 400 copies/mL at screening visit * Serum hemoglobin \< 9.0 g/dl * Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal * Elevations in serum creatinine above 2.5 times the upper limit of normal * Use of drugs known to be contraindicated with levonorgestrel, nevirapine (NVP group only), or efavirenz (EFV group only) within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction tables or the AIDS Clinical Trials Group Drug Interactions Database. * Currently pregnant or postpartum \<30 days at study entry * No concurrent use of other hormonal contraception is allowed during the study period

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 60, 'type': 'ACTUAL'}}

2023-09-01