Prioritizing the evaluation of HIV prevention interventions in pregnancy: Interim results from a randomized, open-label safety trial of dapivirine vaginal ring and oral tenofovir disoproxil fumarate/emtricitabine use in late pregnancy


BACKGROUND: 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 lacking. Here we report interim safety data from the first cohort 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).
METHODS: Eligible women aged 18 to 40 in Malawi, South Africa, Uganda and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants initiated product use between 36 0/7-37 6/7 weeks' gestation and continued 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 with 101 randomized to DVR and 49 to TDF/FTC (Malawi n=27; South Africa n=42; Uganda n=44; Zimbabwe n=37). Demographic and clinical characteristics were similar by study arm. Median age was 25 years (interquartile range [IQR] 21-28) and median gestational age at enrollment was 36.3 weeks (IQR 36, 37). To date, pregnancy outcome data were available for 141 participants (Table). One stillbirth and one neonatal death occurred, both in the TDF/FTC arm. Pregnancy complications were rare, with hypertensive disorders being the most common complication reported (Table).

CONCLUSIONS: In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when the DVR and TDF/FTC were used in late pregnancy and were generally similar to rates observed in the communities where the study is being conducted. These data support plans for subsequent investigation of safety among pregnant women using DVR earlier in pregnancy.