Pharmacologic Strategies to Use the Levonorgestrel Implant in HIV-infected Women

University of Nebraska

Status and phase

Completed

Phase 2

Conditions

Contraception

HIV

Treatments

Drug: Levonorgestrel

Drug: Efavirenz

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02722421

1R01HD085887-01A1 (U.S. NIH Grant/Contract)

0234-16-FB

Details and patient eligibility

About

The purpose of this study is to determine whether increasing the dose of the levonorgestrel subdermal contraceptive implant will overcome a detrimental drug-drug interaction with efavirenz based antiretroviral therapy.

Full description

The investigators research team recently demonstrated that combined use of efavirenz (EFV) based antiretroviral therapy (ART), the only preferred first-line ART regimen in low and middle income countries, with a levonorgestrel (LNG)-releasing implant for one year reduced LNG plasma concentrations by approximately 50% compared to women not on ART. Importantly, the investigators also observed three unintended pregnancies (15%) in the investigators study group of women on EFV-based ART plus the LNG implant, in contrast to the <1% expected failure rate of the implant for women without drug interactions.

This study will determine if increasing the dose of the LNG-releasing subdermal implant effectively overcomes the known pharmacokinetic interaction with EFV- based ART. LNG pharmacokinetic results from the participants enrolled in this dose escalation study (n=28) will be compared to HIV-infected Ugandan women on standard dose LNG without concomitant EFV-based ART.

Enrollment

28 patients

Sex

Female

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Women age 18 years to 45 years
Diagnosed with HIV infection
Desiring LNG subdermal implant as a contraceptive method
Receiving EFV-based ART for a minimum of 3 months prior to screening
Must agree to have concurrent highly effective non-hormonal contraception with a copper intrauterine device (IUD), if not previously medically sterilized.
Participants must have a negative urine pregnancy test at entry and report no unprotected sex since the last menstrual period or in the last two weeks.

Exclusion criteria

HIV RNA > 50 copies/mL at screening visit
Serum hemoglobin < 10.0 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 LNG or EFV within 30 days of study entry. Due to the dynamic nature of drug interactions related to ART, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table.
Currently pregnant or postpartum <30 days at study entry
Concurrent use of other hormonal contraception (Note: use of other forms of hormonal contraception is permissible until time of study enrollment/insertion of LNG implant. Transition from other forms of hormonal contraception to LNG subdermal implant will be accommodated according to LNG product labeling)
For the EFV group, participants determined to be ineligible for IUD placement by the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use
If participation in the study puts the participant at unacceptable risk based on the judgment of the study staff