No Dapivirine Ring Safety Concerns in Third Trimester of Pregnancy

A pregnant woman

(Adobe Stock, anon)

(This article first appeared on ContagionLive.com.)

A woman’s risk of acquiring HIV during pregnancy is estimated to be up to 3 times higher than during other periods. Following pregnancy, the risk is even more significant when many women breastfeed according to a study presented at the Conference on Retroviruses and Opportunistic Infections 2023 (CROI2023) held in February.

A vaginal ring containing the antiretroviral drug dapivirine posed no safety concerns when used in the third trimester of pregnancy, according to results from a study of use of the dapivirine ring during pregnancy. The study was one of only several regarding the use of an HIV prevention product in pregnant cisgender women.

The ongoing phase 3b study, known as MTN-042/DELIVER, was designed to evaluate the safety and acceptability of the monthly dapivirine vaginal ring, a new HIV prevention method approved in several African countries and recommended by the World Health Organization (WHO). Investigators also aimed to collect additional safety data on the use of emtricitabine/tenofovir disoproxil fumarate (Truvada) as daily oral pre-exposure prophylaxis (PrEP) during pregnancy. The study was also designed to be conducted in a stepwise fashion, enrolling 1 group at a time, beginning with women late in pregnancy when the potential risks from drug exposure are lowest, and only proceeding to the next group if an independent review of the data deemed it safe to do so.

“Safety data on the use of these HIV prevention products in this population is vitally important, which is why we designed DELIVER the way we did, enrolling 1 group at a time, to ensure the safety of both mothers and their babies and so that we would be able to report our results in a more timely fashion rather than waiting until completion of the study,” Katherine Bunge, MD, MPH, an assistant professor in the Department of obstetrics, Gynecology, and Reproductive Sciences at the University of Pittsburgh School of Medicine and a protocol chair of DELIVER, said in a statement.

Although animal studies of dapivirine indicate no concerns related to pregnancy or fetal development, before DELIVER, the only human data were from approximately 240 participants who became pregnant while using the dapivirine ring in the phase 3 trials ASPIRE (NCT01617096)and The Ring Study and stopped using the ring upon learning they were pregnant. Notably, there were no significant differences in pregnancy and infant outcomes between women assigned to use the dapivirine ring and those set to use a placebo who became pregnant, suggesting ring use during conception and early pregnancy is not harmful. DELIVER will provide information about the ring when used for extended periods and at different stages during pregnancy. Indeed, with the current results, the study has already contributed to a greater understanding of the ring’s safety in the third trimester of pregnancy.

Cohort 1 enrolled 150 women who were 36-plus weeks (8-9 months) pregnant, of whom 101 were randomly assigned to use the dapivirine ring and 49 to use emtricitabine/tenofovir as oral PrEP. Of the 157 participants in cohort 2, who were between 30 and 35 weeks’ gestation (7-8 months pregnant) when they joined the study, 106 used the ring, and 51 used oral PrEP.