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

HIV Infections Clinical Trial

Official title: An Observational Pharmacokinetic Study to Evaluate Drug-drug Interactions Between Doravirine-containing ART and Hormonal Contraceptives Among Women Living With HIV in South Africa.

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

While DOR-containing ART has been evaluated in two large clinical trials, only 16-17% of the study participants were women and only 6-10% of them were African. In an epidemic, where the gendered majority affected by the disease are women of reproductive age living in Africa, it is imperative to conduct a study evaluating reproductive health outcomes among and specific to African women. Further underscoring the issue is a notable data gap for DOR regarding DDIs with the most common leading hormonal contraceptives.

Our intention is to study potential DDIs between DOR and the most common contraceptive methods used by WLHIV in an African context, which generally include short- (e.g., OCPs/COCs), intermediate (e.g., injectable) or long-acting (e.g., implants or IUDs) methods. Since the drug maker of DOR has already conducted the industry standard PK study with DOR and a COC product, containing ethinyl estradiol and levonorgestrel, which did not demonstrate any bidirectional DDI, the investigators have chosen to exclude this method from the current study. Thus, the current EPIC study focuses on intermediate- and long-acting contraceptive methods, which have different PK profiles than daily administrated oral drugs and may be more susceptible to potential DDIs with DOR.

Participants who are interested in self-selecting and initiating one of the study contraceptive methods listed will be recruited for screening and eligibility assessments. If eligible and enrolled, there will be a 6-week lead-in period with daily use of oral DOR-containing ART followed by contraceptive method initiation of their choice. Study follow-up will take place every 2-4 weeks, at a minimum, for an additional 12 or 24 weeks for a total of 18 or 30 weeks of follow-up depending on the contraceptive method chosen.

The investigators will also enroll a dolutegravir (DTG) + IM DMPA group, who will be followed for 12 weeks, as the comparator group for the DOR + IM DMPA group.

The comparator group for the DOR + ETG implant group will be a historical control group from a similar PK study called PARVI (PK study of ARVs and Implants in Kenya) that is currently being conducted by Dr. Patel and colleagues in Kenya.

The five study groups are summarized below in Table 1.

Table 1: Study groups by ART regimen and contraceptive method choice

Group number N ART regimen and contraceptive method Group 1 21 DOR-containing ART + initiating ETG implant Group 2 21 DOR-containing ART + initiating IM DMPA Group 3 21 DOR-containing ART + initiating SC MPA Group 4 21 DOR-containing ART + initiating non-hormonal IUD Group 5 21 DTG-containing ART + initiating IM DMPA

The co-primary objectives are to evaluate any associations between doravirine (DOR), a newer antiretroviral agent for the treatment of HIV, exposure and hormonal contraceptive use in the four groups of DOR + 1) etonogestrel implant (ETG), 2) intramuscular depomedroxyprogesterone acetate (IM DMPA), 3) subcutaneous medroxyprogesterone acetate (SC MPA), or 4) non-hormonal IUD users by generating mean hormone concentrations at 12 weeks for IM and SC DMPA or 24 weeks for ETG implants and IUD groups; also to evaluate any bi-directional associations between hormonal contraceptive exposure and DOR use by generating mean DOR concentration at 24 hours.

The first hypotheses are: the mean implant hormone concentrations for DOR + ETG implant at 24 weeks after implant placement will be similar (i.e. geometric mean ratio [GMR] within 0.80 and 1.25) to the mean implant hormone concentrations for DTG + ETG implant (historical controls from Dr. Patel's current PARVI study in a similar population in Kenya). The mean MPA concentrations for DOR + IM DMPA or SC MPA at 12 weeks after DMPA/MPA administration will be similar (i.e. GMR within 0.8 and 1.25) to the mean DMPA concentrations for DTG + DMPA (contemporaneous study group). Also, the mean C24 hours of DOR in the ETG implant and MPA groups will be similar to the non-hormonal contraceptive method (i.e. the non-hormonal IUD) group.

The secondary objectives are to measure DOR-containing ART's efficacy, via HIV viral load <40 copies/mL, at 12-24 weeks after contraceptive initiation among women of reproductive age using hormonal and non-hormonal contraceptives.

The second hypothesis is that proportion of women suppressed (defined as HIV viral load <40 copies/mL) at 16-30 weeks after DOR-containing ART initiation will be similar to a contemporaneous or historical comparison of the proportion of women suppressed with non-DOR containing ART from the same study population/sample.

The exploratory objectives are to qualitatively explore decision-making around ART and contraceptive options, study experiences of ART switch, and use of the contraceptive method, including self-administration of SC MPA, and to describe self-reported experiences of social harms and social benefits related to study participation. Also, safety including side effects, satisfaction, and continuation rates of both the hormonal contraceptive method and ART will be assessed.

The third hypothesis is that the safety, satisfaction, and continuation rates of the various contraceptive methods will be similar to each other at 12-24 weeks after contraceptive initiation. The investigators will gain interesting insights into women's decision-making around ART and contraceptive method options and are uniquely positioned to describe experiences of self-administration of SC MPA. ;

Related Conditions & MeSH terms

• Contraception
• Drug-drug Interaction
• HIV Infections

• NCT number: NCT04669678
• Study type: Interventional
• Source: University of Alabama at Birmingham
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 17, 2021
• Completion date: December 2024