PITTSBURGH, March 9, 2021 – If adopted, the monthly dapivirine vaginal ring is the first biochemical HIV prevention method designed specifically for cisgender women, as well as the first long-term method. Looking to the future, researchers from the National Institutes of Health Microbicide Testing Network are hopeful that a vaginal ring that could be used more than a month at a time could be available at some point.
In fact, a 90-day dapivirine ring has passed its first trial, with the results of a Phase I clinical trial reported today at a preliminary meeting of the Conference on Retroviruses and Equine Diseases (CROI) in support for further development.
The study, called MTN-036 / IPM 047, evaluated two ring formulations designed to slowly release the antiretroviral drug dapivirine over a 90-day course, one containing 100 mg of dapivirine and the other. another containing 200 mg. Both formulations were recovering well and delivering target levels of drugs through the three months of use, results that would indicate their potential to provide long-term and lasting HIV protection.
The Nonprofit International Partnership for Microbicides (IPM) is developing a three-month ring, building on its monthly dapivirine ring, which received a positive idea last year from the European Medicines Agency for its use among cisgender women aged 18 and older in developing countries, and shortly thereafter, it was added to the list of World Health Organization (WHO) pre-certified medicines. In January this year, the WHO recommended the ring as an additional HIV prevention option for women at high risk for HIV. IPM is seeking permission for the monthly dapivirine ring in east and south Africa first, and the first of those decisions is expected by mid-year. IPM is also seeking regulatory approval from the U.S. Food and Drug Administration.
“A regulatory permit for the menstrual ring would be a remarkable milestone for women, who have been battling HIV infection in much of the world and who need and deserve a range of safe and effective methods. Hopefully, a longer – lasting dapivirine ring that women can replace every three months may be an alternative available to women in the future, “said Albert Liu, MD , MPH, director of clinical research at the San Francisco Department of Public Health (SFDPH), whose protocol chaired the MTN-036 / IPM 047 study, presented his findings at CROI.
MTN-036 / IPM 047 was designed to evaluate the safety and pharmacokinetics (as the body takes the active drug) of the 100-mg and 200-mg 200-day rings, compared to the monthly dapivirine ring, in which contains 25 mg of active drug. .
The study enrolled 49 HIV-negative healthy women and gender-specified female-born individuals at birth at two MTN-related clinical study sites in the United States: the University of Alabama in Birmingham, and HIV Bridge, linked to both the SFDPH and the University of California, San Francisco.
Participants were randomly assigned to one of three groups: one group used the 100 mg dapivirine ring continuously for 13 weeks; a second group who used the 200 mg ring continuously for 13 weeks; and a third group used the monthly ring, replacing it every four weeks.
All three rings were well received by study participants with no safety concerns. Compared to the monthly ring, the two 90-day rings achieved higher dapivirine concentrations in blood plasma and vaginal fluid, with levels that were 1.3 to 1.9 times higher in plasma and 1.5 to 2.9 times higher in vaginal melancholy. Similarly, cervical tissue density was higher in both three-month cycles compared to the menstrual ring.
These results, along with the results of a bioavailability study that IPM is planning, will be considered in its decision on which of the two formulas to move forward for further development.
“We are thrilled to take the dapivirine ring three months to the next stage of development,” said Bríd Devlin, executive vice president of product development for IPM. “Offering women a range of prevention methods is critical to meeting their sexual and reproductive health needs, including options that work longer that they can use on their own terms.”
In addition to a 90-day dapivirine ring for HIV prevention, IPM is also developing a 90-day ring for both HIV prevention and contraception. In two Phase I studies conducted by the MTN, a dual-ring containing 200 mg dapivirine and 350 mg of the contraceptive hormone levonorgestrel was found to be well tolerated. The results of the latest study, MTN-044 / IPM 053 / CCN019, reported at the Virtual Research Conference for HIV Prevention (HIVR4P) earlier this year, found that the ring was delivering consistent levels of both dapivirine and levonorgestrel continuously for 90 days.
Globally, more than half of people currently living with HIV are cisgender women, and in sub-Saharan Africa, women make up nearly 60 percent of new infections among adults and teens age 15 and older, with unprotected vaginal sex as the main driver of the pandemic.
The MTN is funded by the National Institute for Allergies and Infectious Diseases with joint funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all of which are part of the NIH.
###
More information about the MTN-036 / IPM 047 review can be found at https: /
The MTN is supported by grants from the US National Institutes of Health UM1AI068633, UM1AI068615, UM1AI106707.
About the Microbicide Testing Network
The Microbicide Testing Network (MTN) is an HIV / AIDS clinical trial network established in 2006 by the National Institute of Infectious and Infectious Diseases with joint funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health . Health, all parts of the U.S. National Institutes of Health. Based at the Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international researchers and community and industry partners whose work aims to rigorously evaluate promising microorganisms – results inserted inside the vagina or rectum intended to suppress sex. HIV transmission – from the earliest stages of clinical study to large-scale trials that support the possible licensing of these products for widespread use. More information about the MTN is available at http: // www.
Disclaimer: AAAS and EurekAlert! they are not responsible for the accuracy of press releases posted to EurekAlert! by sending institutions or for using any information through the EurekAlert system.