HIV Viral Reservoirs and Monocyte Activation in HIV-Associated Atherosclerosis

Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): United States


HIV-infected individuals doing well on therapy now face a higher than expected risk of non-AIDS conditions, including cardiovascular disease for reasons that are not clearly understood. This proposal will help to identify the mechanisms that are associated with this increased risk which can identify novel interventions to reduce risk of health conditions such as cardiovascular disease in HIV as well as other inflammatory conditions.

Dr. Hsue is one of the few cardiologists in the world with both extensive research and clinical expertise in HIV and has devoted the last ten years studying cardiovascular disease in the setting of HIV. The initial part of her career was spent 1) establishing a HIV Cardiology Clinic at San Francisco General Hospital (SFGH), 2) developing the infrastructure to perform POR research in the Cardiology Division at SFGH which has included development of a vascular laboratory for clinical research, and 3) performing studies that evaluate the mechanisms underlying HIV infection and cardiovascular disease (CVD). The findings from her work have shown that 1) HIV infection is independently associated with CVD, independent of traditional risk factors or HIV medication, and 2) chronic inflammation in the setting of effectively treated HIV infection underlies this increased CV risk, and 3) identifying therapies to reduce HIV-associated inflammation and CV risk. For her 5 year K24 award proposal, she plans to increase her time spent mentoring junior investigators in the fields of HIV infection, HIV-associated inflammation, and cardiovascular disease for the purpose of helping them to become successful independent researchers in the future. Her K24 proposal will extend upon her current R01 funded investigations by studying the underlying mechanism of HIV-associated atherosclerosis in the setting of treated HIV infection with the following two Specific Aims: 1) To characterize the role of monocyte/macrophage activation in atherosclerotic progression as assessed by carotid artery intima-media thickness (IMT), endothelial dysfunction as assessed by flow-mediated vasodilation of the brachial artery (FMD), and microvascular disease (measured by peak hyperemic velocity) in effectively treated HIV-infected individuals 2) To determine the role of HIV reservoir on atherosclerotic progression, endothelial function, and microvascular disease in effectively treated HIV-infected individuals. The K24 proposal will provide subject visits, vascular imaging, and clinical and laboratory data to support mentoring new investigators in patient-oriented translational research in the field of HIV-related cardiovascular disease.