Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women
- Registration Number
- NCT03282799
- Lead Sponsor
- Catherine Anne Chappell
- Brief Summary
This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected women on efavirenz (EFV)-based antiretroviral therapy (ART) using either a single etonogestrel (ENG) implant or two ENG implants for at least one year.
- Detailed Description
Due to drug-drug interactions between efavirenz (EFV) and progestins, HIV-infected women on EFV-based antiretroviral therapy (ART) and using the etonogestrel implant have significantly lower systemic ENG concentrations than HIV-infected women not on ART. This finding has raised concerns regarding the contraceptive efficacy of the ENG implant for women on EFV-based ART and clinical studies have an increased rate of pregnancies for women on EFV-based ART and using a contraceptive implant. This study a randomized, open-label, longitudinal pharmacodynamic study to compare frequency of ovulation between a control group of HIV-infected women on efavirenz-based antiretroviral therapy receiving standard dose etonogestrel (ENG) implant and a treatment group receiving increased dose ENG implant. The overall goal is to assess the pharmacodynamic significance of the known drug-drug interaction between EFV and ENG and to determine if the increased dose will overcome this interaction. Overall, this study will improve long-acting reversible contraceptive treatment options for women living with HIV and prevent unintended pregnancy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 72
- 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 40 years
- Diagnosed with HIV infection
- Medically eligible for the ENG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use20
- 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 IUD, if not previously medically sterilized.
- Participants must report regular menses (bleeding for 4-8 days at 21 to 35 day intervals) for the preceding 2 month
- 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.
- 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 ENG 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 table45 and the ENG implant product labeling15.
- Currently pregnant or postpartum <30 days at study entry.
- Breastfeeding women within 6 months of delivery.
- Use of hormonal contraception in the preceding 3 months prior to entry
- Participants determined to be ineligible for IUD placement by the WHO Medical Eligibility Criteria for Contraceptive Use46
- Patients with a history of hypersensitivity to ENG implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.
- Presence of any active clinically significant disease or life-threatening disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Increased Dose Etonogestrel Implant etonogestrel implant Two 68 mg (136 mg total) etonogestrel implants Standard Dose Etonogestrel Implant etonogestrel implant Single 68 mg etonogestrel implant
- Primary Outcome Measures
Name Time Method Proportion of Participants That Ovulate During Month 3 3 months Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
Proportion of Participants That Ovulate During Month 6 6 months Proportion of participants that experience at least one ovulation during month 6 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 6 (weeks 21-24). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
Proportion of Participants That Ovulate During Month 12 12 months Proportion of participants that experience at least one ovulation during month 12 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 12 (weeks 45-48). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
- Secondary Outcome Measures
Name Time Method Median Efavirenz Concentration at Enrollment Day 0 Median efavirenz concentrations measured in plasma samples collected at enrollment, prior to insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Proportion of Cervical Mucus Scores Greater Than 10 12 months The proportion of World Health Organization cervical mucus scores that are greater than 10 from weekly samples collected during months 3, 6 and 12 of etonogestrel implant use. A cervical mucus score greater than 10 indicates the mucus is favorable for sperm penetration or lack of contraceptive effect. The cervical mucus score ranges from 0 indicating least favorable for sperm penetration to 15 for most favorable for sperm penetration.
Median Efavirenz Concentration at Week 4 4 weeks Median efavirenz concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Median Efavirenz Concentration at Week 12 12 weeks Median efavirenz concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Median Efavirenz Concentration at Week 24 24 weeks Median efavirenz concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Median Efavirenz Concentration at Week 36 36 weeks Median efavirenz concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Median Efavirenz Concentration at Week 48 48 weeks Median efavirenz concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Median Etonogestrel Concentration at Week 1 1 week Median etonogestrel concentrations measured in plasma samples collected 1 week after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Median Etonogestrel Concentration at Week 4 4 weeks Median etonogestrel concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Median Etonogestrel Concentration at Week 12 12 weeks Median etonogestrel concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Median Etonogestrel Concentration at Week 24 24 weeks Median etonogestrel concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Median Etonogestrel Concentration at Week 36 36 weeks Median etonogestrel concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Median Etonogestrel Concentration at Week 48 48 weeks Median etonogestrel concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Trial Locations
- Locations (1)
Infectious Disease Institute
🇺🇬Kampala, Uganda