The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced today that it would move forward with an open-label extension study of an HIV prevention tool for women: a silicone ring that continuously releases the experimental antiretroviral drug dapivirine in the vagina. The new study builds on recently announced findings from the ASPIRE trial which found that the dapivirine ring safely provided a modest level of protection against HIV infection in sub-Saharan African women. The dapivirine ring reduced the risk of HIV infection by 27 percent in the study population overall and by 61 percent among women ages 25 years and older, but provided no statistically significant protection in women younger than 25 years. This product is one of several HIV prevention tools in development within NIAID’s portfolio of research that could be leveraged to reduce the high incidence of HIV infection among women in sub-Saharan Africa.
Although the data show only partial efficacy for the dapivirine ring, this signal is a welcome development given the rate of infection for women in sub-Saharan Africa. The dapivirine ring merits additional study to begin to answer the scientific questions that remain, and to see if this experimental product can offer increased protection against HIV in an open-label setting in which all participants are invited to use the dapivirine ring.
The new study, also known as the HIV Open-label Prevention Extension (HOPE) or MTN-025, is a multi-site, open-label, Phase 3b trial that will gather additional data on the safety of the dapivirine ring and study participants’ adherence. The study will be conducted by the NIH-funded Microbicide Trials Network which is funded by NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all part of NIH. Eligible volunteers from the ASPIRE study will be invited to participate in HOPE. HOPE participants will have already been informed of whether they received the dapivirine ring or a placebo in ASPIRE, and all will be offered active product and counseled on the efficacy results from the ASPIRE trial. The specific details of HOPE’s research protocol are currently being adjusted to optimize the collection of data on safety, adherence and acceptability of the dapivirine ring. Younger women enrolled in ASPIRE appeared to use the dapivirine ring less consistently than older participants, in whom efficacy was higher.
NIAID reached the decision to move forward with HOPE after consulting with a panel of outside experts including HIV and women’s health physicians, scientists, advocates, ethicists and statisticians at a meeting on March 9 in Bethesda, Maryland, where the results and implications of ASPIRE’s findings were discussed. Meeting participants were asked to discuss the merits and methods of moving forward with further study of the dapivirine ring, given that in ASPIRE it was only moderately effective overall and not effective among the youngest women in the study—those in most urgent need of HIV prevention tools.
Discussion of the ASPIRE trial’s results and firsthand accounts from women living in sub-Saharan African communities highlight the urgent need for discreet, long-acting, effective HIV prevention tools that women control and want to use. The ASPIRE study is the first clinical trial to show a sustained drug delivery product that slowly releases an antiretroviral drug over time can provide partial protection, but it is not expected to be the last.
NIAID currently funds a diverse portfolio of long-acting prevention research, with nine additional products under investigation. The next wave of innovation in HIV prevention could be driven by success from studies on other ring-based forms of protection with different active drugs including the use of tenofovir and Truvada; implants; and long-acting injectables using rilpivirine, cabotegravir, and tenofovir alafenamide. ASPIRE and other studies indicate that adherence to HIV prevention tools like daily oral PrEP can be challenging for some women, particularly young women. Long-acting injectables and implants, which would only require infrequent dosing, offer a potentially promising way to deliver HIV protection in a way that better fits into women’s lives.
Beyond long-acting antiretrovirals, other prevention tools may also hold promise for women. A multinational clinical trial of an intravenously delivered antibody for preventing HIV infection in women is planned to launch in sub-Saharan Africa this spring. The trial will test whether giving women a potent, broadly neutralizing HIV antibody called VRC01 as an intravenous infusion every 8 weeks is safe, tolerable and effective at preventing HIV, answering fundamental questions for the fields of HIV prevention and vaccine research.
In addition to ensuring that optimal HIV prevention products are available for women, additional studies are being planned in both clinical and laboratory settings to understand why the dapivirine ring did not protect the youngest women enrolled in ASPIRE. In the coming months, NIAID will announce awards and additional funding opportunities for researchers to further explore the critical gaps in scientific knowledge on female behavior and biology that have been identified as a result of the age-stratified results from ASPIRE. Together with ongoing studies investigating strategies to improve adherence in women to daily PrEP, this effort will enhance the scientific understanding of women’s unique needs, and help deliver the best evidence-based HIV prevention products for women.