1. Cardiovascular Disease: Predicting Risk and Monitoring Outcomes Monica R. Shah, MD, FACC NHLBI AIDS Coordinator Conference on Retroviruses and Opportunistic Infections March 5, 2013

2.  HIV-Related Cardiovascular Disease (CVD)  NHLBI AIDS Working Group (WG) – Scientific Priorities  NHLBI AIDS Program – Future Initiatives Overview 2

3. AIDS – An Evolving Population AIDS Patients Face Downside of Living Longer January 2008  In the US ~1.2 million people living with HIV; 50,000 new infections each year  By 2015, HIV patients aged 50 and older will account for >50% of HIV/AIDS cases 1  Chronic, non-infectious diseases such as CVD increasing public health problem 1 www.cdc.gov; Slide courtesy P. Hsue

4. HIV-related CVD – Significant Mortality  1,876 deaths among 39,727 patients  Non-AIDS related deaths accounted for 50.5%  ~16% were due to CVD 13 HIV Cohorts 1996-2006 CVD 15.7% Non-AIDS infection 16.3% Non-AIDS Malignancy 23.5% Violence, Substance abuse 15.4% Liver-related 14.1% Other 9.0% Respiratory 3.1% Renal 3% Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:1387-1396 Slide courtesy JS Currier

5. Risk of CVD in HIV vs. Non-HIV Patients HIV – no ART RR 1.61 (1.43-1.81) p<0.001 HIV – on ART RR 2.0 (1.7-2.37) P<0.001 Islam, FM, et al. HIV Medicine; 2012; 13:453-68.

6.  Complex interplay between  Conventional risk factors -Higher rates of smoking, dyslipidemia, hypertension, diabetes -Obesity  Renal disease  Cardio-metabolic adverse effects of ART  HIV infection  Inflammation and Immune Activation HIV-Related CV Disease

7. Inflammation and Immune Activation Gut microbiome Hypercoagulability Aging HIV Infection Hsue, P et al. The Journal of Infectious Disease. 2012; 13: S375-82.

8.  Coronary artery disease  Arrhythmias and sudden cardiac death  Heart failure  Pulmonary hypertension  Hypertension/vascular disease HIV-Related CV Disease

9. 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

10. NHLBI AIDS WG: CV Scientific Priorities Epidemiology Scientific GapsApproaches to Gaps Incidence/prevalence of HIV-related CVD Utilize existing HIV and CV cohorts to examine questions about HIV-related CVD Interplay of HIV, inflammation, ART, co-infections, and traditional risk factors on development of HIV- related CVD Enrich HIV cohort studies with data on CV events/imaging and thrombotic events Enrich ongoing CVD studies with HIV patients

11. HIV/AIDS WG: CV Scientific Priorities Pathophysiology Scientific GapsApproaches to Gaps Mechanisms of the interplay of HIV, inflammation, ART, co-infections, and traditional risk factors Studies of these factors in the progression of atherosclerosis Studies of molecular pathways responsible for chronic inflammation Studies of microbial translocation, viral replication, and inflammation in altering lipid metabolism, endothelial function, immune senescence, and thrombosis Synergy of pathophysiological mechanisms with smoking Mechanistic and imaging studies that elucidate pathogenesis of HIV-related CVD

12. NHLBI AIDS WG: CV Scientific Priorities Prevention & Treatment Scientific GapsApproaches to Gaps Potential differences in the prevention and treatment of CAD Add CV outcomes to HIV trials, increase enrollment of HIV patients in CV trials Actual efficacy and effectiveness of evidence-based therapies in HIV patients Leverage existing CV databases, claims data, and EHR to evaluate CV patterns of care, variation in prevention, diagnosis, and treatment, post-event outcomes, and implementation of evidence-based care Appropriate targets for therapy in HIV patients Collaborate with HIV trial networks early during protocol development Novel therapies to address unique pathophysiology of CAD in HIV patients Conduct pilot trials of novel agents in HIV-related CVD

13.  Multi-disciplinary collaboration  Critical need for HIV and CV researchers to work together to advance field  Leverage existing research resources  Cross-institute collaboration  Training  Training programs that allow clinical and basic investigators to learn fundamentals of HIV & CVD research NHLBI AIDS WG: Research Strategies

14.  Focus on scientific gaps identified by WG  Broadly stimulate science  Promote multi-disciplinary collaboration  Encourage peer-review, investigator-initiated research  Educate scientific community that NHLBI is a primary Institute for AIDS research NHLBI Future Initiatives – Goal 2014

15. Conclusion  Increasing focus on HIV-related CVD  Progress in science  NHLBI uniquely poised to support research in this area