The nonprofit International Partnership for Microbicides (IPM) announced today the start of the first clinical trial of vaginal rings designed to slowly release the antiretroviral (ARV) drug dapivirine over three months to prevent HIV in women. The development of a three-month ring builds on the promise of IPM's one-month dapivirine ring, which is now under regulatory review as the first discreet and long-acting method shown to reduce HIV risk among women.
A three-month ring would increase convenience and reduce annual costs. The results of the Phase 1 trial, known as MTN-036/IPM 047, will inform the design of future clinical studies and a possible regulatory strategy for this next-generation product.
"This study marks an important next step toward providing discreet, long-acting HIV prevention options that women can control themselves," said Dr. Zeda Rosenberg, founder and chief executive officer of IPM. "As long as HIV incidence continues to be alarmingly high among women, IPM will continue developing new and refining existing solutions women can use on their own terms to protect their sexual and reproductive health."
MTN-036/IPM 047 is being conducted by the US National Institutes of Health-funded Microbicide Trials Network (MTN) in collaboration with IPM. The primary objective of the study, being conducted in the United States, is to assess safety and pharmacokinetics (how the body processes the active drug). The study will also collect information on product acceptability and adherence among women in the study. In addition, researchers will monitor for changes in the vaginal microenvironment.
Dr. Annalene Nel, IPM's chief medical officer, said that this is a notable development for women in sub-Saharan Africa, who remain the population group with the highest risk of HIV infection worldwide. "The latest research builds on the findings of two large studies, IPM's Ring Study and the Microbicide Trials Network (MTN)'s ASPIRE, which in 2016 reported that the monthly ring safely helps reduce the risk of HIV infection among women who participated in these studies in Malawi, South Africa, Uganda and Zimbabwe."
Dr. Nel said that the continued research supports findings indicating women are interested in HIV prevention products that act over the course of one month or longer.
About the study
MTN-036/IPM 047 is taking place at two MTN-affiliated trial sites in the United States, the University of Alabama at Birmingham, and Bridge HIV, a San Francisco Department of Public Health site affiliated with the University of California, San Francisco. Both sites have begun screening and enrolling participants.
The Phase 1, randomized, three-arm study will assess the safety and pharmacokinetics of long-acting vaginal rings containing different amounts of dapivirine. Approximately 48 healthy, HIV-uninfected women ages 18-45 who are not pregnant will be randomly assigned to one of three groups: one group will use a vaginal ring designed for three-month use that contains 100 mg dapivirine; one group will use a ring also designed for three-month use that contains 200 mg dapivirine; and for comparison, one group will use the one-month ring containing 25 mg dapivirine.
Participants in the three-month ring groups will not know whether they are using the 100-mg or 200-mg ring, and will use their assigned ring continuously for 13 weeks. Participants in the comparison group know that they are receiving the 25-mg ring, which they insert upon enrollment and then replace at four and eight weeks. All women participating in the study will receive testing and counseling on how to reduce their risk of acquiring HIV and other sexually transmitted infections, and receive male condoms and other health services. Results are expected in late 2018.
Women and HIV
Women bear the brunt of the epidemic globally, making up more than half of all adults living with HIV/AIDS. Women are at especially high risk in sub-Saharan Africa, where young women are more than twice as likely to acquire HIV as young men. Currently available HIV prevention tools have not been sufficient to stem the epidemic among women, who urgently need more options.
In addition to the three-month dapivirine ring, IPM is advancing a pipeline of other products designed to help increase efficacy and meet women's varying needs, including a three-month dapivirine-contraceptive ring that recently completed its first Phase I study, led by MTN, with results expected in 2018. IPM is also developing combination products that leverage the potency of multiple ARVs.