Cell-Type Specific Mechanisms of HIV Cardiomyopathy

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Project Summary By 2030, 73% of people with HIV will be ≥ 50 years of age and 78% will have cardiovascular disease. People with HIV have a 50% increased risk of acute myocardial infarction, a 61% higher risk of heart failure with reduced ejection fraction and > 4 fold higher rates of sudden cardiac death compared to the general population. In addition to traditional risk factors, HIV-associated features such as chronic inflammation and immune dysregulation in the setting of treated HIV infection are strong predictors of cardiovascular disease. However, studies elucidating the pathogenesis of heart failure in HIV have been largely descriptive and have thus provided limited insight into the underlying mechanisms of these disease processes. Thus, we propose to address the pathogenesis of heart failure in people with HIV through investigating the impact of HIV, immune activation and antiretroviral therapies on the broad range of cell types comprising the human heart. Overall, the proposed studies will illuminate underlying mechanisms of HIV cardiomyopathy, which may be translated to the creation of cell-type specific therapies for HIV-related cardiac diseases.