Refining the Maternal and Pediatric Research Agenda: 2020 and Beyond
By Diana W. Bianchi, M.D., NICHD Director, and Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases
As we refine the science-driven HIV clinical research enterprise, we find ourselves at a pivotal moment for the future of maternal and pediatric HIV/AIDS research. Last year, the NIH-supported IMPAACT Network presented research results demonstrating unequivocally that early antiretroviral treatment for women protects their health and prevents transmission of HIV to their babies in utero, during birth and while breastfeeding. This breakthrough sets the stage to tackle other pressing concerns for women and children.
Looking ahead to 2020 and beyond, the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have developed the following priorities for NIH's maternal and pediatric HIV research:
- Prevent sexual transmission in adolescents
- Evaluate HIV vaccines in pediatric populations
- License newer antiretroviral therapy (ART) during pregnancy, at birth, through childhood and adolescence
- Establish ART-free remission from infancy through adulthood
- License the newer tuberculosis (TB) medications during pregnancy, at birth, through childhood and adolescence
- Define new TB treatment and prevention strategies across the lifespan, including developing a vaccine
- Conduct limited studies of co-morbidities, specifically neurologic and cognitive issues
- Evaluate vaccines for other infectious diseases in HIV-exposed and HIV-positive children
Each of these priorities offers a chance to build on the current science while addressing remaining needs. To capitalize on these opportunities, the structure of the pediatric and maternal clinical research enterprise will need to evolve. In a new model, adolescent HIV prevention and vaccine research will be integrated into the proposed HIV prevention and vaccine research networks, with dedicated pediatric and adolescent medicine expertise to help lead the planning, conduct, and analysis of these clinical studies. These studies will also be conducted in collaboration with the NIH Adolescent Medicine Trials Network for HIV/AIDS Interventions to leverage adolescent medicine expertise and site capacity.
For pediatric HIV therapeutics, multiple, distinct research questions need to be addressed. NIAID and NICHD will support a re-focused maternal and pediatric therapeutics clinical research network that will work hand-in-hand with the broader therapeutics network and other groups as appropriate. This approach will foster collaboration and allow trials to move swiftly from planning to execution to publication. Speed is critical for these populations, as we must safely and rapidly connect lifechanging scientific advances with the women and children who need them, while still addressing the remaining therapeutics research questions for these populations. This network will have the laboratory, data center and clinical site capacity to successfully achieve these goals in partnership with the larger, overall therapeutics network and the other networks.
NIH will need to maintain or expand the capacity of current HIV clinical trial sites across prevention, vaccines, and therapeutics research in order to accommodate additional study participants in these key research areas.
Making the best medical care available to women during pregnancy and to infants is an urgent priority. With the IMPAACT 2010 clinical trial, which is expected to begin in the coming months, we aim to pursue licensure of safer, better antiretroviral drugs for use during pregnancy. We expect results from this study by 2020, setting the stage for future research to test therapies licensed for use in adults for new applications in pregnancy, at birth, and throughout childhood and adolescence.
We must develop safe, effective, and desirable HIV prevention methods that fit into the lives of adolescents and young adults. We need a range of tools that will be used consistently by youth at high risk – particularly young women in southern Africa and young gay men of color in the United States. Treatment as prevention is a cornerstone of the global HIV prevention strategy, and partnering with behavioral and social scientists will help improve its implementation among adolescents and young adults. Through implementation research, we can find ways to foster HIV testing for this population, quickly connect HIV-positive youth to treatment, and help ensure their adherence to therapy. This will not only protect the health of young, sexually active adults, but also will set the stage for greater use of protective antiretrovirals during pregnancy, birth and breastfeeding.
The highest priority HIV prevention tool for youths is a safe, effective and durable HIV vaccine. Two experimental HIV vaccine candidates are now in the later stages of testing in adults. As soon as feasible, immunogenicity studies in younger populations will begin on these vaccine candidates. If either demonstrates safety and efficacy, scientists will proceed with larger clinical studies involving adolescents and seek rapid testing and approval for use in even younger populations.
Scientists have reported a handful of cases in which early-treated children born with HIV maintained long-term control of the virus after discontinuing ART. These individuals give hope that we may be able to spare people born with HIV the burden of life-long therapy and the health consequences of long-term immune activation typically associated with HIV disease. Research collaborations across the HIV clinical trial networks will seek to establish ART-free remission – or a functional cure – in early-treated children that can last well into adulthood, and ultimately a lifetime.
TB represents an outsized burden on youth living with HIV and women of childbearing age. We need to identify the best regimens for treating and preventing TB, including a vaccine, and bring those products to licensure for use across the lifespan. Addressing TB supports a key tenet of NIH's HIV research priorities that we better understand and treat HIV-associated co-infections, comorbidities and complications. Two additional pediatric priorities include studies on HIV-associated neurologic and cognitive disorders, and evaluation of novel vaccines for other infectious diseases, such as respiratory syncytial virus and influenza, that can cause substantial morbidity in HIV-exposed and HIV-positive children.
This approach to maternal and pediatric HIV research, which prioritizes existing expertise while leveraging comprehensive knowledge across the NIH HIV/AIDS clinical trial networks, will deliver the tools and knowledge to dramatically reduce the burden of HIV disease among women and children. We welcome your feedback on this approach to the HIV maternal and pediatric research agenda. Please submit your comments and questions online by November 30, 2017.