Safety outcomes among infants whose mothers used the dapivirine vaginal ring or oral PrEP during pregnancy (MTN-042/DELIVER): a randomised phase 3b study

Abstract

Background: HIV acquisition risk during pregnancy remains high and additional data supporting pre-exposure prophylaxis (PrEP) in pregnancy are needed. The aim of the MTN-042/DELIVER study was to evaluate the dapivirine vaginal ring (DVR) and daily oral tenofovir disoproxil fumarate plus emtricitabine use as PrEP during pregnancy. We report infant outcomes following confirmed in-utero exposure.

Methods: This randomised, controlled, open-label, phase 3b study was conducted in four clinical research sites in Malawi, South Africa, Uganda, and Zimbabwe. Pregnant, HIV-negative, healthy women aged 18-40 years were enrolled at 36-37 weeks' (cohort 1), 30-35 weeks' (cohort 2), and 12-29 weeks' (cohort 3) gestation and randomly assigned 2:1 (cohorts 1 and 2) and 4:1 (cohort 3) to receive the DVR (dapivirine 25 mg) or oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg). All infants born to maternal participants were enrolled and included in the primary infant analysis to evaluate infant safety with in-utero exposure to study product. Infant visits were conducted at less than 2 weeks, 6 weeks, 6 months, and 12 months of age. The primary infant composite safety outcome included serious adverse events and grade 3 or higher adverse events. Birth outcomes (livebirth or stillbirth, prematurity), adverse events (including frequency between each study visit), and growth up to 12 months were evaluated and collected. This study is registered with ClinicalTrials.gov (NCT03965923). The trial is completed and the database closed.

Findings: The study was conducted between Feb 7, 2020, and May 13, 2024. In total, 545 infants were included: 147 in cohort 1, 154 in cohort 2, and 244 in cohort 3. Mean intrauterine exposure was 23·3, 59·7, and 113·8 days, respectively. Overall, 545 (99%) of 550 pregnancy outcomes were livebirths. Serious adverse events occurred in 66 (17%) of 398 infants in the DVR group and 15 (10%) of 147 in the oral PrEP group. Grade 3 or higher adverse events occurred in 95 (24%) of 398 and 29 (20%) of 147 infants, respectively, none related to product exposure. 41 (51%) of 81 new-onset serious adverse events occurred by age 6 weeks, and ten (91%) of 11 congenital anomalies were diagnosed by age 6 months. There were no maternal or infant HIV acquisitions.

Interpretation: Over 12 months of follow-up of infants, the DVR and oral PrEP were generally safe, with no composite adverse events related to study product. Together with available maternal safety data, this supports use of the DVR and oral PrEP by pregnant women to prevent HIV.

Funding: US National Institutes of Health.