The overall goal of this research proposal is to prospectively examine the impact of three modern antiretroviral therapy (ART) treatment strategies on the progression of atherosclerosis in treatment-na?ve individuals with human immunodeficiency virus (HIV) infection. The studies proposed will examine and quantify the contributions of ART, cardiovascular disease (CVD) risk factors, immune activation and inflammation on arterial injury and atherosclerosis progression in HIV-infected individuals. The co-principal investigators are an infectious disease specialist and a cardiologist with expertise in the investigation of CVD risk in patients with HIV. They have assembled a multidisciplinary team of investigators that includes two experts in the treatment of HIV, two cardiologists with expertise in atherosclerosis imaging and lipids, an endocrinologist, and an immunologist, and a cardiovascular basic scientist, who, in collaboration with the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group AIDS Clinical Trials Group, will conduct a prospective substudy of A5257, "A Comparative Study of Three Compact, Non-Nucleoside Reverse Transcriptase Inhibitor Sparing Antiretroviral Regimens for the Treatment Naive HIV-1 Infected Volunteers." A5257 is a prospective, randomized clinical trial (RCT) of ART efficacy. Embedding analyses of structural and functional markers of arterial injury and their determinants in a prospective, randomized clinical trial within the ACTG is an efficient and cost-effective approach to understanding the contributions of traditional and HIV-related factors to atherosclerosis progression in individuals with HIV. The proposal includes the following clinical and mechanistic aims:
AIM 1 (Clinical): To examine the effects of three contemporary initial ART treatment strategies on atherosclerosis progression over three years.
AIM 2 (Mechanistic and clinical): To examine the magnitude and time course of the effects of three contemporary initial ART treatment strategies on endothelial function during the first year of therapy.
AIM 3 (Mechanistic): To examine the effects of ART-related metabolic changes on endothelial function and atherosclerosis progression.
AIM 4 (Mechanistic): To examine the effects of ART-related changes in immune function and inflammation on endothelial function and atherosclerosis progression.

Public Health Relevance

To Public Health Statement There are estimated to be 33 million people worldwide who are living with HIV infection. Treatment for HIV infection has improved dramatically over the past twenty years, however there is growing concern that HIV treatments and chronic HIV infection might increase the risk of cardiovascular disease in people living with HIV. The proposed research will help identify the factors that increase the risk of cardiovascular disease in HIV patients and determine the optimal treatment strategies to reduce long-term cardiovascular disease risk in the setting of HIV infection.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-H (S1))
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Mcdonald, Cheryl
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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Stein, James H; Currier, Judith S; Hsue, Priscilla Y (2014) Arterial disease in patients with human immunodeficiency virus infection: what has imaging taught us? JACC Cardiovasc Imaging 7:515-25
Kelesidis, Theodoros; Roberts, Christian K; Huynh, Diana et al. (2014) A high throughput biochemical fluorometric method for measuring lipid peroxidation in HDL. PLoS One 9:e111716
Stein, James H; Brown, Todd T; Ribaudo, Heather J et al. (2013) Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection. AIDS 27:929-37
Brown, Todd T; Chen, Yun; Currier, Judith S et al. (2013) Body composition, soluble markers of inflammation, and bone mineral density in antiretroviral therapy-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr 63:323-30
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Kelesidis, Theodoros; Currier, Judith S; Huynh, Diana et al. (2011) A biochemical fluorometric method for assessing the oxidative properties of HDL. J Lipid Res 52:2341-51