MTN-042

Primary Objectives

• To describe the maternal and infant safety profile associated with study product exposure during pregnancy
• To describe the pregnancy outcomes associated with study product exposure during pregnancy

Study Summary
MTN-042 is a Phase 3b, open-label, multi-site, randomized (2:1 in Cohorts 1-2 and 4:1 in Cohort 3) trial designed to assess the safety, adherence, and acceptability profiles of the dapivirine VR and FTC/TDF oral tablet when used during pregnancy. Approximately 550 healthy, HIV-uninfected women who are 18-45 years of age, pregnant with a single child, and willing to use study product during pregnancy will be enrolled in MTN-042 along with their newborn infants. Participants will be enrolled into one of three cohorts, with onset of dosing period for each cohort to occur within the following gestational age (GA) ranges:

• Cohort 1: 36 0/7 weeks – 37 6/7 weeks 150 women
• Cohort 2: 30 0/7 weeks – 35 6/7 weeks 150 women
• Cohort 3: 12 0/7 weeks – 29 6/7 weeks  250 women

The cohorts will be enrolled sequentially, with pauses between cohorts to review interim safety data. Enrolled maternal participants will be on study product for up to 30 weeks and followed up for up to 36 weeks, depending on GA at enrollment and timing of pregnancy outcome. Enrolled newborn participants will be followed up for approximately 1 year.

The first clinical research site was activated on January 9, 2020. Accrual of Cohort 1 was completed on April 13, 2021. The interim primary results of Cohort 1 were presented at the at the 11th International AIDS Society (IAS) Conference on HIV Science held virtually on July 18-21, 2021. Primary manuscript of Cohort 1 is in development. Cohort 2 was completed to accrual on March 4, 2022. Cohort 3 accrual started in July 2022.

Interim Primary Results from Cohort 1
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. 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. 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.