Washington, DC—Two large trials are now under way in Africa to test whether a vaginal ring containing a potent antiretroviral drug will prevent HIV infection in women, researchers announced here at the International AIDS Conference.
The ring, a silicone matrix containing the antiretroviral drug dapivirine, is designed to remain in place for a month while it continuously releases the drug to the surrounding vaginal tissue.
The option of a discreet and long-acting HIV prevention method would be especially welcome in sub-Saharan Africa, where the ring is being tested. About half of the more than 34 million people living with HIV worldwide are women; in sub-Saharan Africa, nearly 60% of HIV-infected adults are women. Most acquire the infection through unprotected sex; many have few options to protect themselves when a sexual partner refuses to use a condom.
The randomized, placebo-controlled studies are the first phase 3 efficacy trials to assess a microbicide ring for HIV prevention. The trials will be conducted at sites in Malawi, Rwanda, South Africa, Uganda, Zambia, and Zimbabwe.
One trial, called The Ring Study, conducted by the nonprofit International Partnerships for Microbicide (IPM), which developed the ring, will enroll about 1650 HIV-uninfected women aged 18 to 45 years, 1100 of whom will be randomly assigned to receive rings containing dapivirine and 550 of whom will receive rings without the drug. The second trial, ASPIRE (A Study to Prevent Infection with a Ring for Extended Use), funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Mental Health, is being conducted by the Microbicide Trials Network (MTN) and will involve nearly 3500 women in the same age range.
Preclinical and early clinical studies have found “no toxicity signals,” even with higher doses, said Zeda F. Rosenberg, ScD, IPM’s chief executive officer.
Trial participants will be tested during monthly visits for HIV, other sexually transmitted infections, and pregnancy and receive condoms and counseling on how to reduce risk of infection with HIV and other sexually transmitted pathogens. Use of the ring will be discontinued in women who become pregnant or infected with HIV during the study. Women will receive a new ring every month for a year.
Previous studies using antiretroviral drugs delivered in a pill or vaginal gel indicated that the approach can offer women partial protection against acquiring HIV infection, but adherence is a challenge. A vaginal ring placed once a month that offers sustained release of an antiretroviral drug in the vagina could help overcome this problem, said Sharon Hillier, PhD, of the University of Pittsburgh School of Medicine and the MTN’s principal investigator. “If proven effective, I think this will really revolutionize prevention for women.”
Women already participating in The Ring Study, which began enrolling women in April, say the vaginal ring is a better product because of its ease of use, said Saidi Kapiga, MD, ScD, MPH, protocol chair for the study.
Both new trials were designed to detect a 60% decrease in the risk of HIV infection associated with use of the ring, said Jared Baeten, MD, PhD, of the University of Washington in Seattle, the ASPIRE trial’s protocol chair. But the investigators hope the ring will provide higher efficacy than other products because it bypasses the need to remember to use it, he said.