Clonal Hematopoiesis and CV Risk in Patients Living with HIV

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Antiretroviral therapy (ART) has transformed HIV into a chronic disease, dramatically extending the lifespan of people living with HIV (PLWH). As such, the burden of cardiovascular disease (CVD) in PLWH is expected to increase significantly as the current generation ages. PLWH have been shown to be at increased risk for CVD, including sudden cardiac death, acute myocardial infarction, stroke, peripheral arterial disease, and heart failure. The mechanism of elevated risk of CVD in HIV remains unknown, but chronic inflammation is suspected to play a role. There is a unique alteration of the leukopoietic system in HIV, as despite effective ART, HIV production and perhaps low-level replication persist in leukopoietic and lymphoid tissues. Similarly, in the general population clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with a near doubling of risk of coronary heart disease. However, the frequency of somatic mutations in the hematopoietic system (CHIP) in HIV or the association of CHIP with either arterial inflammation or bone marrow activity have not been previously described. Thus, in the proposed study we seek to study the prevalence of CHIP mutations in PLWH with CVD or risk factors for CVD and the relationship of CHIP carrier status with arterial inflammation and bone marrow/spleen activity. We will leverage previously collected blood samples and FDG-PET/CT scans from the SCOPE cohort, including 81 HIV patients with history of CVD or CVD risk factors compared to 29 matched HIV-negative controls. We hypothesize that CHIP prevalence will be higher in the HIV population with CVD, and that CHIP carrier status will be associated with increased arterial inflammation and lymph node and bone marrow activity on FDG-PET/CT. These data will provide important mechanistic insight into how HIV may increase CV risk via the hematopoietic system.