Results reported at CROI showed that 2 cohorts of the ongoing, phase 3 DELIVER study that this form of PrEP modality posed no differences in pregnancy and infant outcomes.
A woman’s risk of acquiring HIV during pregnancy is estimated to be up to three times higher compared to other periods in her life, and following pregnancy, when many women are breastfeeding, the risk is even greater.
A vaginal ring containing the antiretroviral drug dapivirine posed no safety concerns when used in the third trimester of pregnancy, according to results from the first study of the dapivirine ring during pregnancy and one of only a few studies of an HIV prevention product in pregnant cisgender women.
The ongoing phase 3b study, known as 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), as well as to collect additional safety data on the use of Truvada as daily oral pre-exposure prophylaxis (PrEP) during pregnancy. It was also designed to be conducted in stepwise fashion, enrolling one 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 study data deems it is 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 one 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, MPH, MD, an assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and a protocol chair of the DELIVER study, said in a statement.
Though animal studies of dapivirine indicate no concerns related to pregnancy or fetal development, before DELIVER, the only human data was from about 240 participants who became pregnant while using the dapivirine ring in the Phase III trials (ASPIRE 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 assigned 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 it is used for longer periods and at different stages during pregnancy. Indeed, with today’s results, the study has already contributed 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 Truvada 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.