FY 2015 National Institutes of Health TRANS-NIH PLAN FOR HIV-RELATED RESEARCH Prepared by the Office of AIDS Research Jack Whitescarver, Ph.D. NIH Associate Director for AIDS Research and Director, Office of AIDS Research Dedicated to the Memory of SPENCER COX 1968–2012 An AIDS pioneer, treatment activist, research advocate, and friend. Spencer brought a unique energy and commitment to help us build an AIDS research program that is responsive to the epidemic, based on the most promising science, and inclusive of the voices of the community. He advocated for the highest possible scientific standards for clinical trials to provide clear and useful information for the trial participants and for HIV-infected individuals who may benefit from the research in the future. His voice will be missed. FY 2015 Trans-NIH Plan for HIV-Related Research CONTENTS 1 Legislative Mandate INTRODUCTION 3 Overview 4 HIV/AIDS Pandemic 5 NIH AIDS Research Program 10 NIH Office of AIDS Research 11 Trans-NIH Strategic Plan 12 OAR Budget Development Process 13 Extraordinary Opportunities for FY 2015 19 Conclusion PRIORITY: Expanding Basic Discovery Research 21 Etiology and Pathogenesis PRIORITY: Reducing New Infections 30 Vaccines 45 Microbicides 52 Behavioral and Social Science 64 Treatment as Prevention PRIORITY: Improving Disease Outcomes for HIV-Infected Individuals 70 Drug Discovery, Development, and Treatment 87 Research Toward a Cure PRIORITY: Reducing HIV-Related Disparities 97 Racial and Ethnic Populations 105 Women and Girls 113 Research in International Settings 130 Training, Infrastructure, and Capacity Building PRIORITY: Translating Research From Bench to Bedside to Community 136 Natural History and Epidemiology 147 Information Dissemination APPENDICES 152 Planning Groups 183 NIH Institutes and Centers 184 List of Acronyms FY 2015 Trans-NIH Plan for HIV-Related Research Legislative Mandate Section 2353 of the Public Health Service Act requires that the Director of OAR shall: (1) establish a comprehensive plan for the conduct and support of all AIDS activities of the agencies of the NIH; (2) ensure that the Plan establishes priorities among the AIDS activities that such agencies are authorized to carry out; (3) ensure that the Plan establishes objectives regarding such activities; (4) ensure that all amounts appropriate for such activities are expended in accordance with the Plan; (5) review the Plan not less than annually, and revise the Plan as appropriate; and (6) ensure that the Plan serves as a broad, binding statement of policies regarding AIDS activities of the agencies, but does not remove the responsibility of the heads of the agencies for the approval of specific programs or projects, or for other details of the daily administration of such activities, in accordance with the Plan. The law also specifically requires that the Plan provide for basic research, applied research, research conducted by the NIH, research supported by the NIH, proposals developed pursuant to solicitations by the NIH and investigator-initiated proposals, and behavioral and social sciences research. In accordance with the law, the NIH Office of AIDS Research, a component of the NIH Office of the Director, has developed this document. FY 2015 Trans-NIH Plan for HIV-Related Research 1 FY 2015 Trans-NIH Plan for HIV-Related Research Introduction Overview HIV/AIDS Pandemic NIH AIDS Research Program NIH Office of AIDS Research Trans-NIH Strategic Plan OAR Budget Development Process Extraordinary Opportunities for FY 2015 Conclusion Overview In the three decades since AIDS was first reported, the National Institutes of Health (NIH) has been the global leader in research to understand, prevent, diagnose, and treat HIV and its many related conditions. Recent scientific advances resulting from NIH-funded research represent a turning point for AIDS research. New avenues for discovery have been identified, providing possibilities for the development of new strategies to prevent, treat, and potentially cure HIV. The NIH is leading global research efforts to capitalize on those advances, move science forward, and begin to turn the tide against this pandemic. NIH research has resulted in landmark advances that have led to: Co-discovery of HIV, the virus that causes AIDS; Demonstration of the first proof of concept for the feasibility of a microbicide gel capable of Development of the first blood test for the disease, preventing HIV transmission; which has allowed diagnosis of infection as well as ensured the safety of the blood supply; Demonstration that the use of therapy by infected individuals can dramatically reduce transmission The critical discovery of key targets to develop to an uninfected partner; antiretroviral therapy (ART) and multidrug regimens that have resulted in improved life Demonstration of the potential feasibility of expectancy for those with access to and who can pre-exposure prophylaxis (PrEP), that long-term tolerate these drugs; and the development of use of ART regimens by some groups of high-risk treatments for many HIV-associated coinfections, uninfected individuals can reduce risk of HIV comorbidities, malignancies, and clinical acquisition; manifestations, with benefits for patients also suffering from those other diseases; Discovery that genetic variants may play a role in protecting some individuals, known as “elite Groundbreaking strategies for the prevention of controllers,” who have been exposed to HIV over mother-to-child transmission, which have resulted an extended period, from developing symptoms in dramatic decreases in perinatal HIV in the and enabling them to control the infection United States and in low-income countries; without therapy; Demonstration that the use of medical male Critical basic science discoveries that continue to circumcision can reduce the risk of HIV acquisition; provide the foundation for novel research; and The first step inproving the concept that a vaccine Progress in both basic and treatment research to prevent HIV infection is feasible; and discovery efforts aimed at eliminating viral reservoirs in the of two potent human antibodies that can stop body, which is, for the first time, leading scientists more than 90 percent of known global HIV strains to design and conduct research aimed at a cure. from infecting human cells in the laboratory; NIH intramural and extramural researchers have produced two new exciting advances. NIH researchers published the results of studies utilizing potent human neutralizing antibodies that successfully suppressed a form of HIV in primates. This important research could potentially result in a new form of treatment for HIV that could be used as an adjunct to ART and could lead to opportunities for novel research to treat and potentially cure HIV. NIH-sponsored researchers also have made tremendous strides in producing and analyzing proteins that may provide an important new pathway in AIDS vaccine design. The NIH is leading global research efforts to capitalize on all of these advances, move science forward, and begin to turn the tide against this pandemic. FY 2015 Trans-NIH Plan for HIV-Related Research 3 HIV/AIDS Pandemic Despite this progress, the HIV/AIDS pandemic will remain the most serious global public health crisis of our time. The Joint United Nations Programme on HIV/AIDS (UNAIDS) reports that in 2013: More than 35 million people were estimated to be living with HIV/AIDS. About 2.1 million people became HIV-infected (about half of them women), or about 6,000 infected per day. 1.5 million people died of AIDS-related illnesses. In the United States, HIV/AIDS continues to be an unrelenting public health crisis, disproportionately affecting racial and ethnic populations, women of color, young adults, and men who have sex with men. The Centers for Disease Control and Prevention (CDC) estimates that: Approximately 1.1 million people are HIV-infected. Approximately 50,000 new infections occur each year. One in four people living with HIV infection in the United States is female. OFFICE OF THE DIRECTOR OFFICE OF AIDS RESEARCH National Institute Eunice Kennedy Shriver National Institute National Institute National Institute of Arthritis and National Cancer National Institute on Alcohol Abuse of Allergy and on Aging Musculoskeletal Institute of Child Health and and Alcoholism Infectious Diseases and Skin Diseases Human Development National Institute National Institute National Institute of National Institute on Deafness and National Institute on National Eye of Dental and Diabetes and Digestive of Environmental Other Communication Drug Abuse Institute Craniofacial Research and Kidney Diseases Health Sciences Disorders National Institute National Heart, National Human National Institute of National Institute National Institute of of General Medical Lung, and Blood Genome Research Neurological Disorders of Mental Health Nursing Research Sciences Institute Institute and Stroke National Center National Institute of Fogarty National Center National Institute on for Complementary National Library Biomedical Imaging International for Advancing Minority Health and and Alternative of Medicine and Bioengineering Center Translational Sciences Health Disparities Medicine Center for Center for NIH Clinical Information Scientific Center Technology Review FY 2015 Trans-NIH Plan for HIV-Related Research 4 NIH AIDS NIH AIDS RESEARCH PROGRAM Largest public investment in AIDS research Research Program in the world To address this pandemic, the NIH conducts and Encompasses