DSW is a strong advocate of the need for innovation to respond to the health challenges facing the young men and women that we work with in eastern Africa. To acknowledge the achievements made in women’s health, we wanted to give the floor to those who are working at the forefront of innovation in health, we spoke to Zeda F. Rosenberg, CEO of the International Partnership for Microbicides (IPM), shortly after the announcement of results of clinical trial results for the dapivirine ring, the first long-acting HIV prevention method designed for women that has been shown to safely help offer protection against the virus.
DSW: What is the dapirivine Ring? What is it intended to do?
Zeda Rosenberg: The dapivirine ring, which IPM developed over the past decade, is the first long-acting HIV prevention method designed for women that has been shown to safely help offer protection against the virus. The novel product adapts a medical technology commonly used to deliver hormones— the vaginal ring — to instead deliver an ARV drug to prevent HIV over the course of a month. The flexible ring is easy for a woman to insert herself and provides sustained-release of dapivirine locally to the site of potential infection during vaginal sex. Because currently available prevention methods have not done enough to stop the alarming rates of infection among women, particularly in sub-Saharan Africa, the dapivirine ring could be an important new prevention method.
Our readers not being scientific experts, could you walk us through the key results of the trial announced by IPM in February?
Absolutely. Two large-scale clinical trials assessed whether the monthly dapivirine ring could help prevent HIV infection in women and would be safe for long-term use. These two “sister” studies — The Ring Study, led by IPM, and ASPIRE, led by our clinical trial partner the Microbicide Trials Network (MTN) — involved more than 4,500 women across four African countries where women at high risk of infection. In February, both studies found that the monthly ring is safe and did help prevent HIV in women, by approximately 30 percent overall. This means that nearly one-third of women who would have been infected were not. This is the first time that two large Phase III trials have confirmed that a microbicide can safely and effectively offer women protection against HIV.
Importantly, we saw differences in the results by age and level of product use, or adherence. Women over age 21 had higher levels of protection – by up to 56 percent. Conversely, women ages 18-21 saw little to no protection, which we are now working to fully understand. The two studies also saw a strong trend toward higher levels of protection with higher adherence. We anticipate that knowledge of the ring’s safety and efficacy, matched with additional support to help women use the ring more consistently, could increase protection.
What is the ring’s potential impact on women’s health in sub-Saharan Africa?
We believe the ring could have an important impact, because when women can stay free of HIV, not only will they have a better chance for a healthy and productive future but their families and communities will, too. The shockingly high HIV incidence rates we saw in women of all ages in both ring studies paint a stark picture of the great risk women in sub-Saharan Africa face every day — and the urgent need to find a range of new options they can use to protect their health. We are very encouraged that both studies showed a clear trend toward higher efficacy for the ring with consistent use. This means that we could likely achieve much higher protection with stronger adherence to the ring. We are planning an open-label extension (OLE) study that will give former Ring Study participants access to the ring and help us understand how women will use it now that they are aware it can safely help offer protection. That will give us a better gauge of the ring‘s true potential impact. We hope to see increased adherence and efficacy in the OLE study, as seen in recent PrEP OLEs.
One of the interesting results was the efficacy of the Ring for young women under 21 – a group we work with a lot in East Africa. Is there already understanding within the trial as to why the Ring was less effective with them than women a few years older?
It is an important question that is a top priority for us to understand. We know from both studies that the youngest women aged 18-21 saw little to no protection, and that in ASPIRE, they also used the ring the least consistently. This suggests that adherence played a factor in the results, although we cannot rule out that biological or other factors may have had a role. To further understand these results, IPM is conducting additional analyses of data from The Ring Study, which reported results early, and MTN is planning follow-on sociobehavioral research. In addition, our planned OLE study would help us fully understand what factors discourage adherence, and just as importantly, what motivates it. That information will be vital to supporting women, including the youngest women, to use the product consistently in the OLE study so they can get the greatest benefit from it.
We work a lot with young people who are trying to protect themselves not only from HIV but also from other STIs and from unintended pregnancy. Does the Dapivirine Ring have a role to play as a method of contraception?
We believe the ring serves as an exciting platform technology for a new generation of HIV prevention products that also offer contraception to help meet women’s sexual and reproductive health needs, including those of young women. IPM is now advancing a 90-day vaginal ring that combines dapivirine with a contraceptive hormone so that women could benefit from HIV prevention and contraception in a single product. The ring is expected to enter a Phase I safety trial later this year.
With the results that you have now, what are the next steps? When do you think we are likely to see the Ring commercially available for use?
IPM is pursuing two parallel pathways to advance this potential new prevention method for women. First, we plan to apply for regulatory approval for the ring in early 2017, and are hopeful that the first approvals could be received as soon as late 2018 in some African countries. Second, we are taking steps along a public health pathway, starting with the planned OLE study mentioned earlier that would provide former Ring Study participants access to the dapivirine ring while it is under regulatory review. This open-label study would also help provide critical insight into how women integrate the ring into their daily lives when they are aware of its safety and efficacy. Third, we are also working with governments and other partners to determine how the dapivirine could best fit into HIV prevention programs, and coordinate and finance potential access to an approved and affordable ring.
And finally, a question for the longer-term – is there anything in particular, given the experience of the Ring Trial, that IPM would ask of policymakers or donor governments to help accelerate the process of getting potentially life-saving products like the Ring into the hands of women that need them?
The dapivirine ring is a testament to what partnerships can achieve. Multisectoral, multi-country collaborations were essential to getting us to this point, where we may be able to offer women a comprehensive HIV prevention toolkit that includes innovative, self-initiated products like the monthly dapivirine ring and daily oral PrEP. This is a tremendous opportunity, and succeeding will require political will, financial resources, private sector know-how and civil society and community perspectives. The bottom line is: we need everyone to get involved, because women who face the threat of HIV infection every day need access to new prevention options as soon as possible.
Zeda F. Rosenberg, ScD
Dr. Zeda Rosenberg is CEO of the International Partnership for Microbicides (IPM), a nonprofit organization working to develop new HIV prevention products and other sexual and reproductive health technologies for women. Previously, Dr. Rosenberg served as scientific director for the HIV Prevention Trials Network at Family Health International, and as senior scientist for the U.S. National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health. She received her master’s degree in epidemiology and a doctoral degree (ScD) in microbiology from the Harvard School of Public Health.
IPM is a nonprofit organization dedicated to developing new HIV prevention tools and other sexual and reproductive health technologies for women, and making them available in developing countries. Our partnerships with public, private and civil society bring scientific ingenuity, political will and financial resources to bear on developing and delivering products designed to have significant public health impact. IPM has offices in the United States and South Africa. Visit www.IPMglobal.org and follow us on Twitter @IPMicrobicides.