Dapivirine Ring Shown to Reduce HIV-Risk in Women by 54%

In 2016, results from a clinical trial which tested a new monthly vaginal ring to protect against HIV found that the ring was safe and ultimately reduced a woman’s risk of acquiring the virus by about 27%. ASPIRE (A Study to Prevent Infection with a Ring for Extended Use (MTN-020)) had enrolled 2629 women ages 18-45 from Malawi, Uganda, South Africa, and Zimbabwe, areas in which the risk of a woman acquiring HIV are highest in the world. When woman consistently used the ring, which contains the anti-HIV medication, dapivirine, their protection rose to about 56%. With near perfect use, they saw a reduction in risk of upward of 75%.

At the completion of the trial, women who participated in ASPIRE were given the opportunity to participate in HOPE (HIV Open-label Prevention Extension (MTN-025)), an open-label study of the dapivirine ring. (Women who participated in a sister study, The Ring Study, were given the opportunity to enroll in the DREAM study.) The HOPE trial began in August 2016 and a total of 1407 former ASPIRE participants enrolled. The preliminary results have revealed that the reduction in the risk of HIV infection is even better in the HOPE trial than the other 2 trials, and women’s use of this new form of HIV protection is even higher.

These positive interim results, and more on the HOPE trial, were recently presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI).

Contagion^® spoke with Jared Baeten, MD, PhD, professor of global health, medicine and epidemiology at the University of Washington in Seattle, Washington, who shared with us the differences between ASPIRE, The Ring Study, and HOPE (see video).

Women were able to enroll in the HOPE trial without using the ring, yet according to a statement from International Partnership for Microbicides (IPM), the developers of the dapivirine ring, 92% of the women who joined the trial said they would use the ring. In addition, 89% of the returned rings had residual drug levels that indicated the ring had been used “at least some of the time within the last month,” according to the study authors. Conversely, in the ASPIRE trial, these numbers came in around 77%.

These adherence results mirror those seen in open-label extension studies that occurred after phase 3 trials of the oral pre-exposure prophylaxis (PrEP) pill Truvada. In the studies, adherence to Truvada was improved when compared to the original studies, according to the IPM statement.

The interim results also indicate that the rate of new HIV infections seen in the HOPE trial is 1.9; lower than was seen in the ASPIRE trial. In addition, those women who adhere to the ring in the HOPE trial have seen a 54% reduction in their risk of acquiring HIV.

Dr. Baeten spoke about the implications of these positive interim results (see video).

To determine the HIV incidence at this interim stage, the investigators used statistical modeling and bootstrapping. These results, while promising, should be viewed with caution, according to the study investigators, as they are not the final results of the study. Women in both the HOPE and the parent ASPIRE trial received counseling on HIV prevention, access to condoms, and further services during their participation on the trial. Therefore, we questioned whether or not the use of condoms could have had an impact on the HIV incidence rates reported in the interim results. Dr. Baeten discussed the potential impact of condoms, as well as the limitations of the study in his interview. (see video).

If it gets approved, the dapivirine ring “would be the first biomedical HIV prevention product developed specifically for women—and the first long-acting method,” according to the IPM statement. And, women in the United States and Europe may soon be able to use the ring. Dr. Baeten remarked on the future of the dapivirine ring in his interview (see video).

The approval of the dapivirine would also bring a much-needed choice into the methods patients can take PrEP, according to Sharon L. Hillier, PhD, professor and vice chair of the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and principal investigator of the MTN who shared in a statement that, “Women have told us that they want to have options, and that the ring is appealing to them because it is an HIV prevention option that is more like a reproductive health product than a medicine. So, the take-home message from these 2 open-label studies of the ring couldn't be more clear, and that is that monthly use of the dapivirine ring could provide a new way for women to reduce their risk of HIV.”

IPM is currently seeking regulatory approval of the dapivirine ring based on results of ASPIRE and The Ring Study, and several supporting studies.

Additional studies of the 1-month dapivirine ring, include:

• REACH (MTN-034/IPM 045), to evaluate the ring and oral PrEP among adolescent girls and young women; and
• (MTN-041, MTN-042, MTN-043), studies of the 1-month ring in breastfeeding and pregnant women.

Next-generation dapivirine ring studies include:

• (MTN-036/IPM 047), study of a 3-month ring; and
• (MTN-030/IPM 041, MTN-044), studies of a ring that also contains a contraceptive.