As we begin to discuss the restructuring of NIAID's clinical trials networks, let us first focus on the Institute's HIV prevention research agenda. Developing new biomedical tools that can safely and effectively prevent HIV acquisition and transmission is critical to addressing the global HIV/AIDS pandemic. Currently, we are exploring several promising HIV prevention strategies that, if proven successful, could have a significant impact on reducing the incidence of new infections. These strategies include microbicides — gels, foams, creams, and other formulations designed to prevent sexual transmission of HIV — and pre-exposure prophylaxis (PrEP), attempting to block HIV infection by providing antiretroviral medicines to people who are not infected with HIV but who are at high risk for infection. HIV vaccines are also a major focus of our prevention research efforts, but we will discuss that area specifically in an upcoming blog post.
Vaginally or rectally applied microbicides could potentially provide women and men with a means of protecting themselves against sexually transmitted HIV infection. Non-human primate studies have shown that antiretroviral-based microbicides protect against HIV infection, and these types of products are now being tested in people. Nearly a dozen clinical studies are currently evaluating different microbicide candidates and delivery methods, such as the VOICE trial, which is comparing oral antiretroviral medicines to an antiretroviral-based topical gel for HIV prevention. That study is being conducted by the NIAID-supported Microbicide Trials Network. Future microbicide research efforts will focus on evaluating new products, formulations and routes of administration with the goal of finding a safe and effective microbicide that is reliably used by its intended population.
Using antimicrobial drugs prophylactically has been shown to be effective in preventing other infectious diseases, such as malaria, and lends hope that a similar strategy using antiretroviral medicines could do the same for preventing HIV acquisition. The strategy also has been shown to block HIV transmission from infected mothers to their infants and currently is being explored further in the multinational clinical trial known as the PROMISE study. That trial, which is being conducted by the NIAID-supported International Maternal Pediatric Adolescent AIDS Clinical Trials network, is examining how antiretroviral regimens may best reduce the risk of HIV transmission from infected pregnant women to their babies during pregnancy and breastfeeding while preserving the health of the children and mothers.
In addition to the PROMISE study, several other studies are underway that are evaluating PrEP among different populations with some results expected later this year or early into 2011.
Moving forward in designing and evaluating microbicides and PrEP, questions related to adherence and behavior must be considered. These prevention tools will only be effective if they are used properly and consistently, and we need to be sure that benefits of the interventions are not obviated by increased risky behavior.
- Have we considered the most important scientific priority areas for HIV prevention? If not, what are we missing?
- Among the priority areas that we have identified, what is the appropriate balance to pursue (e.g., should we devote the majority of our attention to one area in particular)?
- How will a “test and treat” research agenda be affected if it is discovered that expanded HIV testing and linkage to care and antiretroviral treatment provides both a clinical benefit to the individual infected with HIV and a reduction in HIV transmission to the larger population?
- Are there remaining research issues associated with preventing mother-to- child HIV transmission?
- What are the emerging opportunities in combination prevention? What threshold of reduced HIV incidence in animal models should be sufficient to initiate a clinical trial?
- What other HIV prevention-related questions should be considered as important scientific priorities?
In addition to microbicides and PrEP, there is a range of other possible approaches to preventing HIV acquisition and transmission that could be evaluated, including strategies designed to increase utilization of HIV testing, behavioral interventions aimed at reducing HIV risk, and approaches to reducing alcohol or drug use, which contribute to increased risk for HIV infection. Additionally, structural interventions – those focused on at-risk communities groups as compared to individuals – could be evaluated as well.
Integrating proven HIV prevention strategies is another important area of exploration. As the number of validated prevention approaches increases, we need to determine optimal combinations in terms of impact and cost-effectiveness. Given that we are unlikely to find a prevention strategy that is fully effective for everyone, a multi-pronged approach tailored to different communities is the best way to end the global HIV/AIDS pandemic. This will require strong partnerships with the Centers for Disease Control and Prevention (CDC), the President's Emergency Plan for AIDS Relief, and other NIH institutes and centers. For example, NIAID and CDC are preparing to launch the HIV Prevention Trials Network (HPTN) 065 study, or TLC+, a feasibility study that will involve expanded HIV testing, better linking of those who test HIV positive to medical care and treatment, and improving adherence to HIV treatment.
I hope that you will give some thought to these questions and provide us with your feedback. In the next blog entry, I’ll discuss NIAID's therapeutic research priorities.