Among women who were provided the dapivirine monthly vaginal ring, the almost 90% who used it at least sometimes reduced their rates of HIV infection by 50% lower than expected without the ring. Women who used the ring all or most of the time reduced their risk of HIV infection by at least 56%, according to preliminary results from the HIV Open Label Extension (HOPE) study, presented at the Conference on Retroviruses and Opportunistic Infections, in Boston, MA.
The HOPE study is a follow-up to the phase 3 ASPIRE clinical trial, a National Institutes of Health (NIH)-funded study, which showed that a silicone ring capable of continuous-release of the anti-HIV drug dapivirine in the vagina could safely reduce the risk of HIV infection by 27%.
“The findings from the ASPIRE study told us how much protection the dapivirine ring afforded the study population as a whole, which included women who used the ring often, sometimes, or not at all,” explained National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, MD. “However, we know that HIV prevention tools work only if people use them. The findings of the exploratory analysis reported today give credence to the hypothesis that greater adherence to the dapivirine ring translates into a higher level of protection. The HOPE trial will provide additional data that either reinforce or refute this hypothesis.”
After the ASPIRE trial, researchers led by Elizabeth R. Brown, ScD, principal investigator, Statistical and Data Management Center of the NIH-funded Microbicide Trials Network (MTN), conducted this exploratory analysis of the HOPE study. Using data from ASPIRE, they sought to gather data on how women use the ring knowing it is safe and moderately effective, and assess the association between compliance to the dapivirine ring and protection from HIV infection.
“We did these new analyses to better understand the potential degree of protection the dapivirine ring could provide,” said Dr. Brown. “These results are encouraging, finding that protection could be significant with consistent use.”
For the HOPE study, all subjects were offered the dapivirine ring, to be used vaginally for up to 12 consecutive months. In the first 3 months, women attended monthly study visits where they got the ring. They returned for quarterly visits, where they can obtain three rings at a time, based on a schedule that more closely mimics how the ring would be distributed in a real-world setting.
The study will take place at all of the former ASPIRE study sites in Malawi, South Africa, Uganda, and Zimbabwe.
Setting up for HOPE
In the ASPIRE study, investigators measured the amount of dapivirine left in the rings returned by subjects at 1 year. After ASPIRE ended, Dr. Brown and colleagues used these measurements and data on HIV infection during the study to assess the relationship between adherence to the ring and the risk of HIV infection. They included almost 2,400 of the original women from the ASPIRE study.
As of October 2017, 89% of the rings returned have residual dapivirine levels that are consistent with some use in the previous month. This contrasts with findings from the ASPIRE trial, in which 77% of the returned rings had residual levels of dapivirine consistent with some use in the previous month.
These findings suggest that adherence in the HOPE trial is currently 16% higher than in the ASPIRE cohort. Researchers noted, however, that serum dapivirine levels were not included in this interim analysis.
HIV infections have occurred in HOPE subjects at a rate of 1.9 new infections per 100 person-years of follow-up.
Dr. Brown and colleagues found that adherence was associated with an at least 56% reduction in the risk of HIV infection, and that high adherence was associated with a risk reduction of potentially 75% or higher. Low adherence was not associated with significant protection from HIV infection.
Final results from the HOPE trial are expected in 2019.
“It would be ideal for women to have discreet HIV prevention tools that they want to use and can control by themselves,” said Carl W. Dieffenbach, PhD, director of the Division of AIDS, NIAID, which was the primary funder of the study. “Interim data from the HOPE open-label extension study appear to be sending a positive signal about the desirability of the anti-HIV vaginal ring in a setting more like the real world than previous trials. We look forward to the final results from this study, which should provide more definitive information.”
The HOPE study is sponsored by the International Partnership for Microbicides (IPM), which developed and provided the dapivirine vaginal ring.