Pharmacokinetic and Clinical Associations Between Doravirine-Containing Antiretroviral Therapy and Injectable and Implantable Hormonal Contraceptive Methods Among Women Living With Human Immunodeficiency Virus in South Africa.

Abstract

Drug resistance and intolerance of dolutegravir-containing antiretroviral therapy (ART) are rising in low- and middle-income countries, resulting in a potentially increased use of doravirine-containing ART use. There are knowledge gaps regarding doravirine and hormonal contraceptive drug-drug interactions among women living with human immunodeficiency virus (HIV). We conducted a 5-parallel-group, prospective pharmacokinetic study among women living with HIV aged 18-45 years in Johannesburg, South Africa, between November 2021 and February 2024. We included a sixth, historical comparator group from a Kenyan study. After a ≥6-week lead-in period with doravirine-containing ART, participants initiated injectable medroxyprogesterone acetate (MPA), implantable etonogestrel (ENG), or nonhormonal intrauterine device contraception and were observed every 2-4 weeks for an additional 12 or 24 weeks. We analyzed serum MPA and ENG and plasma doravirine or dolutegravir concentrations per visit, using validated liquid chromatography-mass spectrometry assays. We assessed log-transformed concentrations of each drug with geometric mean ratios (90% confidence intervals) and a multivariate model adjusted for age and body mass index. We described safety, tolerability, and effectiveness (HIV RNA <40 copies/mL) of doravirine-containing ART. A total of 128 participants are included in this analysis. There were no significant reductions in the MPA, ENG, or doravirine concentrations. A total of 8 (3%) adverse events grade ≥2 were considered attributable to doravirine-containing ART and 22 (8%) to the contraceptive method. ART satisfaction was 100%, and viral suppression at study exit ranged from 86% to 96%. We found no detrimental bidirectional drug-drug interactions and few adverse events between doravirine and hormonal contraceptives.