Evaluation of Pharmacokinetic Drug-drug Interactions Between Hormonal Contraceptives and Doravirine-containing ART Among Women Living With HIV in South Africa

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

The study investigators are conducting an observational, parallel group pharmacokinetic (PK) study among women living with HIV (WLHIV) already on 1st line antiretroviral therapy (ART) and virally suppressed, 18-45 years old (inclusive), to evaluate any bidirectional drug-drug interactions (DDIs) between doravirine (DOR)-containing ART and hormonal contraceptive methods. This PK study will enroll women in five distinct groups, each with 21 participants (total of 105 participants), and follow them for approximately 18-30 weeks.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborators: Merck Sharp & Dohme LLC; Wits Reproductive Health and HIV Institute
• Treatments: Etonogestrel; Medroxyprogesterone; Medroxyprogesterone Acetate

Criteria

Inclusion Criteria:

• HIV-positive

• Currently on 1st line ART (namely EFV- or DTG-containing ART),

• Have documented or confirmed viral suppression for HIV (defined as <40 copies/mL) within 3 months prior to study screening and after the start of the current ART regimen

• Contraception use:

a) Not currently on reliable contraception and intending to or willing to initiate use of study hormonal/non-hormonal contraceptive methods 6 weeks after DOR lead in period (and willing to continue use for subsequent 12 to 24 weeks),

• Able and willing to comply with all study procedural requirements,

• Able and willing to provide informed consent for study participation in either English or Zulu,

• Able and willing to provide adequate locator information, as defined in site SOPs,

• Negative pregnancy test at Screening and Enrollment, and

• At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation.

Exclusion Criteria:

• Currently on 2nd line, 3rd line, or salvage ART regimens,

• Currently pregnant or intending to become pregnant within the next 6 months,

• Currently breastfeeding or intending to breastfeed within the next 6 months,

• Use or anticipated use of drugs for the duration of the study period known to interact with hormonal implants, DMPA/MPA, or the respective ART regimen

• Current or planned concomitant use of other hormonal contraceptives,

• Currently obese (BMI≥30),

• Has any of the following laboratory abnormalities at Screening Visit:

1. Haemoglobin abnormality Grade 2 or higher

2. Calculated creatinine clearance less than 50 mL/min by the Schwartz Equation

• Per participant report at Screening and Enrollment, intends to do any of the following during her study participation period:

1. relocate away from the study site

2. travel away from the study site for a time period that would interfere with product resupply and study participation

• Per participant report and/or clinical evidence of any of the following:

1. Known adverse reaction to any of the study products (ever),

2. Participation in any other research study involving drugs, medical devices or vaccines within 60 days of enrollment,

3. At Enrollment, as determined by the PI/designee, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder, metabolic bone disease or infectious disease,

• We will test for hepatitis B and if participant has the infection, they will be excluded from the study. We also will test for hepatitis B immunity and the participant is not immune, we will offer the vaccination against hepatitis B infection.

• Has any other condition that, in the opinion of the PI/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.