Dapivirine Vaginal Ring, Oral PrEP Safe for HIV Prevention in Pregnancy

DENVER — The monthly dapivirine ring to reduce risk of HIV in women showed similar safety outcomes as oral pre-exposure prophylaxis (PrEP) when used throughout the second and third trimesters of pregnancy, according to a phase IIIb open-label trial in sub-Saharan Africa.

Premature births occurred in 4% of those with the ring, compared with 6% in the oral PrEP group and a local background rate of 12.7%. Two stillbirths unrelated to the study drug occurred in the dapivirine group, Felix Mhlanga, MBChB, MMed, of the University of Zimbabwe College of Health Sciences Clinical Trials Research Centre in Harare, reported here at the Conference on Retroviruses and Opportunistic Infections.

The findings, combined with those of two previous cohorts of this study, support the use of the dapivirine vaginal ring as an HIV prevention option in pregnant people at risk of HIV, Mhlanga said.

“It is probably common knowledge that pregnancy represents a period of heightened HIV acquisition for a variety of reasons, physiological and sociobiological,” Mhlanga told attendees. “As such, we need interventions to prevent a major catastrophe in maternal and infant outcomes.”

PrEP is one of the best available, but not everyone can use PrEP, he said, and it’s important to have a prevention menu of options for people. While 11 countries in Africa are already rolling out the dapivirine ring for HIV prevention, more evidence on its use in pregnancy is needed, Mhlanga said.

Prior research has established the ring’s safety in early pregnancy. In two previous cohorts of this study, safety was assessed in people 36 or more weeks pregnant who used the ring for 4-6 weeks and in people 30-35 weeks pregnant who used the ring for 7-12 weeks. This study, the third and final cohort of the MTN-042 DELIVER study, assessed the ring’s safety in people starting at 12-29 weeks pregnancy who used it for up to 30 weeks.

The study enrolled 251 adults, ages 18-40, with singleton pregnancies in Uganda, Malawi, Zimbabwe, and South Africa. All had ultrasound-confirmed gestational age and no history of pregnancy complications. The participants were a mean 25 years old, and two-thirds had had a prior pregnancy, with an average 1.6 prior full-term births.

The mean gestational age at enrollment was 23.3 weeks, with 26% at 12-19.9 weeks gestation and the rest at 20-29.9 weeks. Nearly all (97%) the expected maternal visits were completed. The mean gestational age at delivery was 39.6 weeks, with a mean time from enrollment to delivery of 16.4 weeks.

In the two previous cohorts of the DELIVER study, participants were randomized 2:1, but this cohort was randomized 4:1, with 202 participants assigned to use the monthly dapivirine ring and 49 participants using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP until delivery or 41 6/7 weeks gestation.

The stillbirth rate of 1% in the dapivirine group was lower than the 4% local background rate based on a review of 10,138 records. One miscarriage before 20 weeks occurred in the dapivirine group.

Any hypertensive disorder of pregnancy occurred in 9% of the dapivirine ring group and 14% of the oral PrEP group, compared to the background rate of 10.5%. No cases of severe eclampsia occurred in either group, and no infectious complications occurred in either group.

Peripartum/antepartum hemorrhage occurred in 3% of the dapivirine group, with no cases in the PrEP group (no background rate was available). Postpartum hemorrhage occurred in 1% of the dapivirine group, with no cases in the PrEP group and a background rate of 3.2%.

None of the mothers died or had HIV seroconversion. At least one adverse event occurred in 12% of the mothers and 16% of the infants in the dapivirine group and in 8% of the mothers and 4% of the infants in the PrEP group. Rate of congenital anomalies was 5% in the dapivirine group and 4% in the PrEP group.

The study was limited by its inclusion of only uncomplicated singleton pregnancies in urban or peri-urban areas and its lack of power to detect rare pregnancy complications.

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