By Carl W. Dieffenbach, Ph.D., Director, Division of AIDS, National Institute of Allergy and Infectious Diseases
Microbicides have been viewed as an important and potentially revolutionary way to protect women and men from sexual acquisition of HIV. Investigational preventive microbicides contain anti-HIV drugs, and are applied to the vagina via sponges, gels, creams, rings or suppositories, and the rectum via douches, gels or creams. These types of delivery mechanisms allow for the active ingredient to bathe the area, conceivably providing protection.
Microbicides can be discreet, and they are applied by the user – important concepts for those who lack agency in relationships or face stigma for choosing to protect themselves. Because of these potential advantages, microbicides remain a promising, possible component of an HIV prevention toolkit, alongside existing options like condoms, voluntary medical male circumcision, pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and viral suppression.
In particular, microbicides are thought to offer advantages for women, should a modality reach regulatory approval. Developing safe, effective and desirable prevention tools for women has been a longstanding goal for the National Institutes of Health, and is a top priority for the next iteration of the clinical research enterprise.
In 2016, one such microbicide delivery method demonstrated safety and a degree of efficacy. Two large clinical trials in southern Africa found that a silicone ring that continuously releases the antiretroviral drug dapivirine in the vagina safely provided a modest level of protection against HIV infection in women. The ASPIRE study, conducted by the Microbicide Trials Network, found that the ring reduced the risk of HIV infection by 27 percent in the study population overall and by 61 percent among women ages 25 years and older, who used the ring most consistently.
Later exploratory analyses indicated that effectiveness may be significantly higher when the ring is used as directed. In consultation with the research community, NIAID launched the HOPE Trial, an open-label extension study to see if this experimental product can offer increased protection against HIV in an open-label setting in which all participants are invited to use the dapivirine ring, and to understand why the ring provided no statistically significant protection in women younger than 25 years. The product is now under regulatory review, and may become available to women outside of research settings soon.
As NIH works to refine the HIV clinical trial networks during a competitive renewal process, all approaches to HIV prevention must be evaluated to determine how they can best contribute to ending the pandemic. As a biomedical research funding agency, NIH’s goal is to facilitate the development of prevention products that can conceivably fully protect an individual from acquiring HIV. By proving that a prevention concept can work for a population, NIH’s research investment enables a company or other organization to develop a product at scale. To move the needle on the pandemic, new HIV prevention tools must be acceptable to the user, and must offer benefits that outweigh adherence challenges. Developing an array of safe and effective choices that suit individuals – people in diverse settings, of all genders, with unique needs – is critical.
While microbicides offer promise, and we are pleased to see the ring progress to regulatory review, the remaining microbicide research field faces substantial barriers to developing successful products. The candidate microbicides currently in the research pipeline have limited proven efficacy, and it has not been demonstrated that the most vulnerable users would choose or adhere to these products. Coitally dependent products, including condoms, require use with each sex act, creating a major adherence challenge. For women, microbicide products designed for vaginal use do not protect during anal sex. Further, topical agents deliver a concentrated level of protection to a targeted tissue, but if that tissue tears, or the virus moves through the layer of protection, HIV infection can occur. It is essential that the microbicide field complete ongoing studies to assess the feasibility of success for these modalities and continue to innovate new delivery methods that clear these obstacles.
Despite the challenges that microbicides must overcome, we remain interested in and supportive of a preclinical agenda for concept discovery that focuses on improving desirability, adherence and efficacy. Microbicide research began in earnest in the early 1990s and has evolved significantly over the years. It is now time for the next generation of solutions to be designed and tested. This will require creativity and innovation beyond what is already in clinical studies. If novel approaches that are likely to offer effective, acceptable protection are proposed, they will be evaluated to determine how these could fit into NIH’s broader HIV prevention research program.
Microbicide researchers have been trailblazers in conceiving and developing tools intended to protect women from HIV. Understanding a woman’s unique biology and developing optimal interventions for women has been a blind spot for medical research throughout history. Microbicide researchers stepped in early on to fill that gap in HIV research, and history proves their prescience as the pandemic has evolved to now disproportionately affect young women in southern Africa. In 2016, new infections among young women between ages 15-24 were 44 percent higher than they were among men in the same age group. Developing prevention tools to protect young women is inarguably one of the highest priorities for NIH HIV research and will continue to be paramount as the research agenda through 2027 is developed.
Since beginning this conversation in January, I have heard from many who feel microbicide research has an important role to play in the future. I agree that it can, and we need to make sure that we honor the lives of women and men by developing easy-to-use, effective prevention tools. Innovative ideas have been a hallmark of HIV research, and I look forward to working with the community to create the next generation of prevention tools, building on our substantial investments in this field.
As always, I welcome and encourage your feedback as we develop NIH’s refinement plans. Submit comments and questions by November 30, 2017, online.