AIDS Research at the NHLBI: A Program in Evolution NHLBI AIDS Team June 7, 2013

AIDS Research at the NHLBI  Changing Profile of AIDS  NHLBI AIDS Program -Key Actions in  NHLBI AIDS Program -The Future

Adults and Adolescents Living with an AIDS Diagnosis, by Sex, – United States and 6 U.S. Dependent Areas

AIDS – An Evolving Population AIDS Patients Face Downside of Living Longer, January 2008 The number of people 50 and older living with HIV in U.S. has increased 77% from 2001 to By the year 2015, HIV patients aged 50 and older will account for half of all HIV/AIDS cases in the U.S. 1 Chronic disease conditions such as cardiovascular disease are an increasing important health issue in this population. 1

Many Age-Associated Diseases More Common in Treated HIV Disease Than in Age-Matched Controls Multiple factors likely explain this increased risk, including co-morbid conditions and antiretroviral drug toxicity Cardiovascular disease COPD Anemia Liver failure Kidney failure Cognitive decline Frailty Immune system Cancer (non-AIDS) Bone fractures/osteopenia Chronic inflammation may underlie many of these conditions

NHLBI Is the Third Largest NIH Institute NIH Institute Budgets NCI$5 B NIAID$4.7 B NHLBI$3 B NIGMS$2 B NIDDK$1.8 B

National Heart, Lung, and Blood Institute Mission: Provide global leadership for research, training, and education programs to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives.

 Independent Budget  2013 – $64 million  Separate Payline  2013 – Comparable to Early Stage Investigator  AIDS Specific Receipt Dates  AIDS Specific Review  AIDS Study Sections  Clinical trials reviewed in CLTR 8 NHLBI AIDS Program: Key Facts

 Team  Mission Statement  Working Group  Initiatives  Website  Professional Meetings  Key Large Projects Key Actions in

Key Action: NHLBI AIDS Program Organized Team

NameNHLBI AIDS Team Role Monica Shah, MDNHLBI AIDS Coordinator Renee Wong, PhDCV Team Leader Hannah Peavy, MDLung Team Leader Sandra Colombini-Hatch, MDLung Team Leader Simone Glynn, MDBlood Team Leader Shimian Zou, PhDBlood Team Leader Myron Waclawiw, PhDStatistics Tony Creazzo, PhDReview Kristin Burns, MDPediatrics/CV Team Anu Rao, MDCV Team Ryan LombardiGrants Management Lis Caler, PhDLung Team NHLBI AIDS Team: Organization

Key Action: NHLBI AIDS Program Developed Mission Statement

The NHLBI AIDS Program provides global leadership for research, training, and education programs to promote the prevention and treatment of HIV-related cardiovascular, pulmonary, and hematologic disease. The NHLBI AIDS Program believes that critical research in this area will result in discovery that enhances the survival and quality of life of patients with HIV, and may also lead to knowledge that benefits all patients with heart, lung, and blood disease. NHLBI AIDS Program – Mission Statement

Key Action: NHLBI AIDS Program Conducted Working Group

AIDS WG: Recommendations Scientific GapsApproaches to Gaps Epidemiology Incidence/prevalence of HIV-related HLB disease Utilize existing cohorts to examine questions about HIV-related HLB disease Enrich ongoing HLB studies with HIV patients Pathophysiology Mechanisms of the interplay of HIV/inflammation, ART, co-infections, microbiome, and traditional risk factors in development and progression of HIV- related HLB disease Conduct fundamental studies that elucidate pathogenesis of HIV-related HLB Treatment & Prevention Efficacy and effectiveness of evidence- based therapies in HIV patients Novel therapies to address unique pathophysiology of HIV-related HLB disease Add HLB outcomes to HIV trials to understand the effects of HIV therapies on end-organ complications Increase enrollment of HIV patients into HLB trials Collaborate with HIV trial networks early during protocol development

AIDS WG: Recommendations Research Strategy Themes ApproachDetails CommunicationProfessional HLB societies Other Institutes Collaboration and TeamworkCollaborate with other IC to understand how to best leverage resources and develop new programs Develop inter-disciplinary investigator teams Leveraging ResourcesUtilize existing HIV cohorts and studies and enrich with HLB endpoints, increase enrollment of HIV patients into HLB trials Utilize infrastructure of HIV networks to develop HLB focused trials

Key Action: NHLBI AIDS Program Developed New Initiatives

 Disseminate goals of NHLBI AIDS Program  Recognize NHLBI as a primary funding Institute for AIDS research  Focus on scientific gaps identified at workshop  Broadly stimulate science  Promote multi-disciplinary collaboration  Encourage peer-review  Timeline  NIH Guide Fall 2013  January 2014 receipt date AIDS Initiatives: Guiding Principles

Initiative Number of Awards Number of Years Total Budget RFA (R01, R21) Basic HIV-Related HLB Research FY14 325$72 million RFA (R01) Clinical HIV-Related HLB Research FY14 225$67 million RFA (U19) Beyond HAART: Innovative Approaches to Cure HIV FY15 35$28 million Planned AIDS Initiatives

Key Action: NHLBI AIDS Program Developed AIDS Website

NHLBI AIDS Website

Key Action: NHLBI AIDS Program National Presentations

 2013 – Conference on Retroviruses and Opportunistic Infections  2013 – American Heart Association  2013 – American Thoracic Society National Presentations

Key Action: NHLBI AIDS Program Publications and Activities

Key AIDS Programs: Heart Key Publications HIV Infection and the Risk of Acute Myocardial Infarction Freiberg, M, JAMA Internal Medicine, 2013 HIV infection associated with 50% increased risk of AMI beyond that explained by recognized risk factors. Arterial Inflammation in Patients with HIV Grinspoon, JAMA, 2012 Increased arterial wall inflammation by PET in HIV pts. vs. non-HIV controls with similar cardiac risk factors; associated increased markers of monocyte & macrophage activation. Project Officer (PO): Cheryl McDonald, MD

Key Large AIDS Programs: Lung ProgramKey Publications Longitudinal Studies of HIV- Associated Lung Infections and Complications PO: Hannah Peavy, MD Contributors to diffusion impairment in HIV-infected persons Gingo, MR, Eur Respir J, 2013 Lung HIV Microbiome Project PO: Sandra Colombini-Hatch, MD Widespread Colonization of the Lung by T. whipplei in HIV Infection Lozupone, C, Am J Respir Crit Care Med, 2013 ProgramGoals Mechanisms of HIV-Associated Lung Disease PO: Hannah Peavy, MD Investigate cellular and molecular events underlying HIV- associated lung disease Identify disease sub-phenotypes, biomarkers to predict risk and molecular targets to design therapeutic

Key AIDS Programs: Blood ProgramKey Study REDS-III South Africa Obstetric Hemorrhage and HIV Brazilian Sickle Cell Disease and HIV HIV molecular surveillance in the US, Brazil, China and South Africa Cell Therapy Engraftment and in vivo selection of HIV-protected stem cells (5R01HL116217) Allogeneic Transplant in HIV Patients (NCT ; BMT CTN 0903) Test Develop ment HIV Selectest (REDS-II) ProgramKey Publication REDS-II Genetic diversity of recently acquired and prevalent HIV infections in US blood donors Delwart, J Infect Dis HIV genotypes and primary drug resistance among HIV seropositive blood donors in Brazil, Sabino, J Acquir Immune Defic Syndr, PO: Simone Glynn, MD Shimian Zou, PhD

 Increasing burden of HIV-related HLB disease  NHLBI uniquely poised to support research in this area  NHLBI AIDS Program – Long Term Plan  Develop NHLBI AIDS portfolio  Enhance communication and collaboration  Cultivate HIV-HLB scientific community  Results  Research that improves outcomes for HIV patients – and all patients with HLB disease NHLBI AIDS Program: The Future