This week, the National Institutes of Health (NIH) announced that it is funding the first clinical trial to test the safety and acceptability of both the dapivirine vaginal ring and oral pre-exposure prophylaxis (PrEP) for HIV prevention in pregnant cisgender women. The study, called DELIVER, plans to enroll 750 HIV-negative, pregnant women aged 18 to 40 in southern and eastern Africa. The women will either be given the monthly dapivirine vaginal ring or a daily oral tablet from enrollment through the end of their pregnancy.
As the NIH explained in its press release, research has found that in women of reproductive age, the risk of acquiring HIV is two to four times greater during pregnancy and the first six months after childbirth than at other times. This is particularly concerning in sub-Saharan Africa, where women have an average of 5.1 births, meaning they spend much of their reproductive years pregnant or postpartum.
Limited evidence from existing studies suggests that both oral PrEP and the dapivirine ring are safe for pregnant women and their fetuses; however, there has not yet been a study specifically designed to prove their safety during pregnancy.
HIV Prevention Methods
Oral PrEP is a tablet containing two anti-HIV drugs. Numerous studies have found that when taken daily, PrEP is the most effective tool at preventing sexually acquired HIV. The World Health Organization (WHO) originally recommended that PrEP be offered as a prevention choice to men who have sex with men in 2014 but expanded that definition the following year to cover all population groups at substantial risk of HIV infection. (Priority populations are defined as those with an HIV incidence of about 3 per 100 person-years or higher.) In some areas, this includes women.
The dapivirine ring is a newer method of HIV prevention made specifically for women. It’s a flexible silicone ring that releases the antiretroviral drug dapivirine locally, as a way to prevent infection during vaginal sex with minimal absorption of the drug elsewhere in the body. Women insert the ring into the vagina, and it works for a month before they need to replace it. The dapivirine ring is under regulatory review by the Food and Drug Administration (FDA) in the United States and also by the European Medicines Agency (EMA).
Three large clinical trials of the dapivirine ring—called the ASPIRE study, the HOPE study, and the DREAM study—suggest that the ring is accepted by women and fairly effective in preventing HIV. The ASPIRE study, which concluded in 2016, enrolled over 2,600 women in four sub-Saharan African countries. It found that the dapivirine vaginal ring reduced HIV by 27% among all women enrolled in the trial and by 61% among women ages 25 and older (younger women appeared to use the ring less consistently than other participants). Using statistical modeling, the DREAM study—which concluded in 2019—found that the overall HIV incidence rate among women using the ring was 63% lower than would be expected without it.
The New Study
The new DELIVER study will build on this research to determine if the dapivirine ring is safe during pregnancy and will also look at the safety and acceptability of oral PrEP. It is designed to complement another NIH-funded trial that is testing the safety, acceptability, and efficacy of oral PrEP during pregnancy and the first six months after birth in adolescents and young women aged 16 to 24. This study is also being conducted in southern and eastern Africa.
Women in the DELIVER study will be randomly assigned to receive either the ring or PrEP pills at some point in their pregnancy. They will continue to use their assigned method until the end of their pregnancy or 42 weeks, whichever comes first. The study team will record any medical problems or deaths among the women, as well as pregnancy losses, premature live births, and birth defects in infants. The babies born from women in the study will be studied until they are approximately one year old. The study will also look at the level of the drugs in infants and evaluate changes to women’s genital microenvironment. Researchers will also use questionnaires to determine the extent to which women accept and correctly use the product they are assigned.
According to the NIH: “The design of the DELIVER trial has been carefully reviewed and approved by the communities, national health authorities, ethicists and other key stakeholders where the study will take place.” As an extra precaution, women will be enrolled in phases, starting with those in the latest stages of pregnancy, when there would presumably be less risk to the developing fetus. Subsequent phases will enroll women earlier and earlier in pregnancy, but between each phase, an international panel of experts who are not affiliated with the trial will conduct a safety analysis to determine if the study can continue.
Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, said in the press release, “Women need reliable HIV prevention methods that they know are safe during pregnancy for themselves and their babies. This new clinical trial will provide important data on the safety of PrEP and the dapivirine ring during pregnancy and will help.”