November 23, 2011
In the first clinical trial of a vaginal ring combining two antiretroviral (ARV) drugs, researchers from the Microbicide Trials Network (MTN) are collaborating with the International Partnership for Microbicides (IPM) to evaluate whether the ring is safe for use in women. If the ring does prove to be safe, it could be considered for further testing, and eventually be evaluated for its effectiveness as a microbicide for protecting women against HIV infection through vaginal sex.
The trial, which is funded by the National Institutes of Health and goes by the name MTN-013/IPM 026, is evaluating a ring that contains dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) and the entry inhibitor Selzentry (maraviroc). The dapivirine-maraviroc ring is the first combination microbicide to enter clinical trials. It is also the first vaginal microbicide containing an entry inhibitor. The belief is that combining the two drugs, which act at different points in the HIV life cycle, may provide greater protection against HIV than a single drug alone.
The ring was developed by IPM, a non-profit product development partnership headquartered in Silver Spring, Maryland, in collaboration with Queens University Belfast (Belfast, Northern Ireland).
Globally, women comprise half of the 34 million people living with HIV. In most cases, women acquire HIV through unprotected heterosexual sex with an infected partner. Because the use of condoms is often not an option, there is an urgent need for effective prevention strategies that women can control themselves. To that end, vaginal microbicides in the form of a gel or a ring are being developed to provide women with new tools to protect themselves against HIV.
MTN-013/IPM 026, which is now screening potential participants, will enroll 48 healthy, HIV-negative women ages 18-40 at the University of Pittsburgh, Fenway Institute in Boston and the University of Alabama at Birmingham. Researchers will evaluate the ring's safety and how well women like or are willing to use the ring. In addition, different tests will be performed to help determine how much of each drug is taken up by the cells usually targeted by HIV and whether drug levels are sustained throughout the four weeks the ring is worn. Women will wear their assigned ring for 28 days. Different tests and procedures will be conducted during this time as well as during a 24-day follow-up period.
"IPM has been a pioneer in developing vaginal rings for delivery of antiretrovirals. Our collaboration marks an important juncture for the field as we begin to explore drugs with different mechanisms of action and methods that we hope will give women new, easy-to-use options for preventing HIV," remarked MTN Principal Investigator Sharon Hillier, PhD, who is professor and vice chair for faculty affairs, and director of reproductive infectious disease research in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh School of Medicine.
"Our partnership with MTN on the first combination microbicide to enter clinical trials is an important milestone for the HIV prevention field," said Zeda F. Rosenberg, ScD, IPM chief executive officer. "With extensive pre-clinical data on both drugs to support the combination ring's development, we hope this product will one day expand women's HIV prevention options and open the door to developing other combination HIV prevention methods."
Next year, the MTN will launch a Phase 3 effectiveness trial of the dapivirine-only ring. The study, called ASPIRE -- A Study to Prevent Infection with a Ring for Extended Use -- will enroll approximately 3,475 women at sites in five African countries.
As part of IPM's strategy to license the dapivirine ring, IPM will conduct The Ring Study (IPM 027), which will be done in parallel with ASPIRE, and collect long-term safety and efficacy data about the ring among approximately 1,650 women at multiple research centers in Africa.