Survival of HIV-infected patients worldwide has remarkably improved with the use of anti-retroviral therapy. Metabolic and cardiovascular complications associated with HIV infection and its treatment are becoming more evident as this patient population ages with chronic viral infection. Metabolic and inflammatory changes in HIV-infected patients including dyslipidemia, insulin resistance, fat redistribution with abnormal adipocytokine secretion, alterations in monocyte subsets, and T-cell activation may increase the risk of atherosclerotic disease.
The aims of the proposed grant are: 1) to determine the prevalence and degree of subclinical coronary atherosclerosis using CT angiography in patients with HIV compared to agematched control subjects without HIV infection, 2) to examine risk factors for coronary atherosclerosis in HIV patients, specifically evaluating the potential roles of adipocytokines, monocyte subsets, and T cell activation in atherosclerosis development, and 3) to perform a randomized, placebo-controlled, physiologic study in HIV patients with subclinical coronary atherosclerosis comparing the effects of statin therapy vs. placebo on plaque inflammation (as determined by 18F-fluorodeoxyglucose positron emission tomography), inhibition of plaque progression (as determined by coronary CT angiography), monocyte subsets and T cell response. Characterization of the atherosclerotic disease burden as well as identification of risk factors associated with atherosclerotic disease in HIV will be instrumental to guide the future design of appropriate prevention and treatment strategies for the HIV patient population. To achieve these aims, the candidate will be mentored by internationally recognized experts from several relevant disciplines in patient-oriented and translational research, endocrinology, cardiology, inflammation biology, HIV medicine, cardiac imaging, and biostatistics. Their mentorship and the strength of the candidate's institutional support will provide a well-suited academic environment to conduct this research and to nurture the candidate's career development. This K23 career development award will help the candidate to acquire the additional research skills to achieve her goal of becoming an independent patientoriented translational investigator.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Scott, Jane
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Massachusetts General Hospital
United States
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Srinivasa, Suman; Fitch, Kathleen V; Petrow, Eva et al. (2014) Soluble CD163 is associated with shortened telomere length in HIV-infected patients. J Acquir Immune Defic Syndr 67:414-8
Zanni, Markella V; Fitch, Kathleen V; Feldpausch, Meghan et al. (2014) 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque. AIDS 28:2061-70
Tawakol, Ahmed; Lo, Janet; Zanni, Markella V et al. (2014) Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients. J Acquir Immune Defic Syndr 66:164-71
Fitch, Kathleen V; Srinivasa, Suman; Abbara, Suhny et al. (2013) Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 208:1737-46
Zanni, Markella V; Abbara, Suhny; Lo, Janet et al. (2013) Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS 27:1263-72
Lo, Janet (2011) Dyslipidemia and lipid management in HIV-infected patients. Curr Opin Endocrinol Diabetes Obes 18:144-7
Burdo, Tricia H; Lo, Janet; Abbara, Suhny et al. (2011) Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 204:1227-36
Lo, Janet; Abbara, Suhny; Shturman, Leon et al. (2010) Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 24:243-53
Lo, Janet; You, Sung Min; Liebau, James et al. (2010) Effects of low-dose growth hormone withdrawal in patients with HIV. JAMA 304:272-4
Lo, Janet; Abbara, Suhny; Rocha-Filho, Jose A et al. (2010) Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AIDS 24:2127-30

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