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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL092792-05
Application #
8319638
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Scott, Jane
Project Start
2008-09-02
Project End
2013-10-31
Budget Start
2012-08-01
Budget End
2013-10-31
Support Year
5
Fiscal Year
2012
Total Cost
$141,750
Indirect Cost
$10,500
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Lo, Janet; Lu, Michael T; Kim, Elli A et al. (2016) Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus. Open Forum Infect Dis 3:ofw062
Nou, Eric; Lu, Michael T; Looby, Sara E et al. (2016) Serum oxidized low-density lipoprotein decreases in response to statin therapy and relates independently to reductions in coronary plaque in patients with HIV. AIDS 30:583-90
Lo, Janet; Lu, Michael T; Ihenachor, Ezinne J et al. (2015) Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV 2:e52-63
Srinivasa, Suman; Fitch, Kathleen V; Lo, Janet et al. (2015) Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine. AIDS 29:443-52
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
Lo, Janet; Rosenberg, Eric S; Fitzgerald, Michael L et al. (2014) High-density lipoprotein-mediated cholesterol efflux capacity is improved by treatment with antiretroviral therapy in acute human immunodeficiency virus infection. Open Forum Infect Dis 1:ofu108
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
Nolte, Julia E H; Neumann, Till; Manne, Jennifer M et al. (2014) Cost-effectiveness analysis of coronary artery disease screening in HIV-infected men. Eur J Prev Cardiol 21:972-9
Zanni, Markella V; Kelesidis, Theodoros; Fitzgerald, Michael L et al. (2014) HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque. Antivir Ther 19:805-11
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

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