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

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 + etonogestrel (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