By Carl W. Dieffenbach, Ph.D., Director, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health
May 12, 2017
Since the previous round of renewals for the NIH clinical trials networks, the approach to global HIV prevention has been marked by dramatic change. The ambitious scale-up of treatment and new options for prevention have transformed the HIV landscape both for those at risk of acquiring the disease and for researchers investigating new ways to prevent HIV infection.
In 2011, the primary finding from HPTN 052 was published, demonstrating that when antiretroviral therapy durably suppresses HIV to undetectable levels, the risk that the treated individual will sexually transmit the virus to an HIV-negative partner is negligible. The study later showed that this effect can be sustained, provided there is adherence to therapy. Recognizing that HIV treatment has the power not only to preserve and improve individual health but also to reduce HIV transmission, the Joint United Nations Program on HIV and AIDS (UNAIDS) in 2014 set a bold goal of meeting ambitious benchmarks for HIV diagnosis, treatment, and suppression. These “90-90-90” goals set targets for diagnosing 90 percent of all people living with HIV, delivering antiretroviral therapy to 90 percent of those diagnosed, and achieving viral suppression for 90 percent of those on treatment by 2020.
As we have seen, when implemented in communities, treatment as prevention can be remarkably successful at preventing the spread of HIV infection. Pre-exposure prophylaxis, or PrEP, is another relatively new but highly effective prevention strategy in which at-risk HIV-negative people take one pill a day to prevent acquisition of the virus. However, developing a safe and effective vaccine would be the ultimate game-changer because vaccines can be distributed to at-risk populations more cost effectively and do not present the user-adherence challenges as do certain other prevention tools. An HIV vaccine holds lifesaving potential and is the National Institute of Allergy and Infectious Diseases’ (NIAID) highest priority for HIV/AIDS research.
The pursuit of an HIV vaccine and other separate tools to prevent transmission traditionally have been siloed individually in discrete administrative organizations, both in HIV clinical research networks and within NIAID’s own organizational structure. Yet, research on a vaccine increasingly intersects with other prevention modalities. For example, today’s clinical trials investigating an HIV vaccine candidate must take into account the availability of PrEP as a practice occurring within the communities where trials are conducted.
These new and increasingly important intersections require thoughtful approaches for the future. Looking ahead to when universal treatment and PrEP are standard of care within communities participating in these trials, there will be creative ways of bringing together the research agendas in non-vaccine prevention with those of vaccine researchers. As we move to trial designs that offer PrEP as part of the control arm, adaptive designs or even open-label designs should be considered. Given these expected changes, we should plan to integrate vaccine research into a broader HIV prevention research context in 2020.
HIV vaccine researchers Lawrence Corey, MD, and Glenda E. Gray, MBBCH, FCPaed(SA), explored this concept in a recent commentary published in Proceedings of the National Academy of Science. They write, “…the unsolved biomedical research question for the global HIV epidemic is how to develop an effective system of primary HIV prevention. … Both test and treat interventions and vaccines of partial efficacy leave holes in our ability to contain the epidemic. Inadequate levels of diagnosis and viral suppression result in low rates of prevention, as does a partially effective vaccine of less than prolonged durability. Both approaches achieve the best effect when used together.”
To use and evaluate concepts together, we need to create new and improved prevention modalities and refine the ways in which current tools are implemented. Without the implementation of these tools, the virus will continue to spread. We need a combination of strategies to prevent new infections. An effective, durable HIV vaccine will be a key component of this prevention portfolio.
We are now determining the focus and priorities of the HIV clinical trials networks through 2027, and preparing to work within a new HIV prevention paradigm. Imagine that in 10 years we have long-acting prevention and treatment strategies effective for 6 months to a year. Imagine that we are closing in on an HIV vaccine that has an efficacy of at least 60 percent. In these scenarios, HIV prevention is a united concept. The products themselves may be discrete tools, but they work together in a holistic manner.
The 19-year-old woman in Durban who is considering what HIV prevention tool will work for her may decide to use a vaccine with a vaginal ring. A 19-year-old man in Kenya may opt for adult medical male circumcision and a vaccine. Here in the United States, a 30-year-old man sitting in an Atlanta clinic may consider a vaccination combined with a daily pill, or perhaps a long-acting injectable. A young woman in Oakland may opt for a vaccine and contraceptive implant, because prevention of pregnancy remains her top priority. Our goal is to develop the tools to offer people a variety of safe and effective choices that work well within their lives and provide sustained, systemic protection.
To prepare for the day when many more safe and effective choices await those who need them, we should prepare our HIV clinical trials networks to confront the realities of this changing prevention landscape. We need to identify those questions that will require discussion and collaboration across what is currently two distinct yet inextricable research disciplines. There are approaches where focused prevention networks could synergize to evaluate their novel concepts in integrated, large trials.
The advantages of combining HIV prevention and HIV vaccine clinical research in a single network structure have been demonstrated over the past year with the launch of the AMP studies of a broadly neutralizing antibody in two large-scale, multinational efficacy trials. However, a wider application of this structural model would need to account for the intensive, early-phase studies required for vaccine research, and may necessitate specialized support. Developing a combined network approach would require careful consideration of some existing programmatic segmentation.
It took many advances to reach the point in HIV research when such issues are even on the table. As we move into what we believe will be a prolific period of discovery, we must continue to position the science-driven HIV research enterprise to deliver the innovative, efficient results needed to turn the corner on the HIV/AIDS pandemic. We welcome your thoughts and comments. Please share your feedback at NIAIDnetworkrefinement@mail.nih.gov or use the comment form.