Phase 3 Trial to Assess Dapivirine Ring for Safety in Pregnant Women

Various alternatives to a daily pill for HIV pre-exposure prophylaxis (PrEP) have are being evaluated to ease the burden on patients and increase adherence to the regimen.

The National Institutes of Health (NIH) has launched the first clinical trial evaluating the safety of a monthly dapivirine ring among pregnant women in eastern and southern Africa. The NIH-funded trial will also assess the safety of daily oral emtricitabine/tenofovir disoproxil fumarate, to compare the acceptability and use of these 2 HIV prevention measures.

The vaginal ring works by slowly releasing the non-nucleoside reverse transcriptase inhibitor dapivirine, and is replaced every month.

In their press release about the new trial, NIH officials pointed to the unfortunate fact that for women of reproductive age, the risk of HIV acquisition ranges from 2 to 4 times greater than average during pregnancy and the 6 months following childbirth.

The trial, known as “DELIVER: A Phase 3b Safety Study of the Dapivirine Ring and PrEP in Pregnant Women,” will enroll 750 women who are not living with HIV between 18-40 years of age who have are currently pregnancy.

Enrolled participants will be randomly assigned to receive either the dapivirine vaginal ring or PrEP in a 2-to-1 ratio. Participants will use the regimen until the end of their pregnancy or 42 weeks gestation, depending on which time point occurs first.

Women will be enrolled in 4 stages, starting with 150 women in the latest stages of pregnancy, after which the study will be paused for safety analysis prior to the enrollment of the next group. Infants will be enrolled after birth for additional safety assessment.

If safety is found acceptable by an independent panel, the process will be repeated with 150 women at 30-35 weeks gestation, followed by 150 women at 20-29 weeks gestation, and will conclude with 300 women at 12-19 weeks gestation.

Women will be followed for 6 weeks after pregnancy, and newborns will be followed until they are about 1 year old.

The investigators will record any adverse events or deaths, as well as any birth defects that occur. Live births, premature births, and pregnancy losses will also be observed. The study team will also assess acceptability of the study products through questionnaires.

Previous study has suggested that both PrEP and the dapivirine ring are safe for women, but this is the first clinical trial addressing the matter directly and in pregnant women.

Previous phase 3 clinical trials pointed to the dapivirine ring being well-tolerated and approximately 30% effective at preventing HIV acquisition through vaginal sex. In one study, the dapivirine ring appeared to reduce HIV-risk in women by 54%.