Background:
Pregnancy represents a high-risk period for HIV acquisition. The monthly dapivirine vaginal ring (DVR) has been clinically shown to reduce HIV risk with no safety concerns in nonpregnant reproductive-aged cisgender women; however, data during pregnancy are limited. Here we report safety data from the first two cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (MTN-042/DELIVER, NCT03965923.)
Methods:
Eligible pregnant individuals aged 18 to 40 in Malawi, South Africa, Uganda, and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants in cohort 1 initiated product use between 36 0/7-37 6/7 weeks gestation; in cohort 2 product use was started at 30 0/7- 35 6/7 weeks gestation. All participants continued product use until delivery or 41 6/7 weeks gestation. Pregnancy outcomes and complications reported at the time of delivery were assessed and summarized using descriptive statistics and compared to local background rates obtained through a systematic chart review (MTN-042B).
Results:
One-hundred and fifty participants were enrolled into cohort 1 with 101 randomized to DVR and 49 to TDF/FTC. One-hundred and fifty-seven participants were enrolled into cohort 2 with 106 randomized to DVR and 51 to TDF/FTC. Demographic and clinical characteristics were similar by study arm for each cohort. In cohort 1, one stillbirth and one neonatal death occurred, both in the TDF/FTC arm. One stillbirth and one neonatal death occurred in cohort 2, both in the DVR arm. The prevalence of preterm delivery was 2% in cohort 1 and 6% in cohort 2. In both cohorts, pregnancy complications were rare, with hypertensive disorders being the most commonly reported, and generally similar to local background rates (Table 1). There were no cases of fever of unclear etiology or preterm premature rupture of membranes reported. In cohort 2, there was 1 (1%) case of chorioamnionitis in the DVR arm and 1 (1%) of endometritis in the TDF/FTC arm, and 2 (4%) of puerperal sepsis in the TDF/FTC arm.
Conclusions:
In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC were used in the third trimester of pregnancy and were similar to rates observed in the communities where the study is being conducted. These data support plans for subsequent investigation of DVR safety earlier in pregnancy.
Maternal pregnancy complications by study arm