Interim data from two studies of a dapivirine vaginal ring—DREAM and HOPE—lend further credence to the potential benefits of using the device for HIV prevention. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI), the results build on data presented at CROI 2016, which showed that the ring was well tolerated and reduced HIV risk by about 30% overall in two large Phase III clinical trials in Africa—The Ring Study and ASPIRE.
Interim analyses of DREAM, a Phase IIIb study, showed an increase in ring use over its parent Phase III study, up from 83% in the Ring Study to 96% in DREAM, with use varying from intermittent to consistent. The interim analyses also suggest that the overall HIV incidence rate among women in the DREAM study is 54% lower than would be expected without its use, based on statistical modeling. That finding is limited in that DREAM is an open-label study with no placebo group.
DREAM is being conducted by the International Partnership for Microbicides (IPM) at six former Ring Study sites in South Africa and Uganda and enrolled 940 women aged 20 to 50. The interim analysis was conducted on 900 women enrolled in the study as of September 2017. The risk reduction data were calculated using a bootstrap sample. That is, the observed HIV-1 incidence rate of 1.8% in the participants was compared to an incidence rate of 3.9% in a simulated placebo group with similar characteristics.
Results nearly identical to those from DREAM were reported at CROI for the HOPE trial, a parallel open-label Phase IIIb study being led by the US National Institutes of Health-funded Microbicide Trials Network (MTN). Dream is scheduled for completion in December and HOPE in October, with final results in 2019.
The dapivirine ring is flexible silicone and provides sustained release of the antiretroviral (ARV) drug locally to the site of potential infection during vaginal sex with minimal systemic absorption. Women insert the product themselves and replace it every month. IPM is also developing a version of the dapivirine-only ring that would be changed only once every 3 months and would offer increased convenience and lower annual costs, and a ring that combines the ARV drug with a contraceptive.
IPM is seeking a positive opinion about the dapivirine ring’s device’s safety, efficacy, and quality from the European Medicines Agency and the World Health Organization. Once that is received, the organization will submit applications for approval of the product to the South African Health Products Regularity Authority and the US Food and Drug Administration.