There is controversy regarding the degree to which HIV infection and/or highly active antiretroviral therapy (HAART) contribute to the risk for cardiovascular disease (CVD). The Multicenter AIDS Cohort Study (MACS) is a unique long-standing multi-center observational longitudinal cohort study of men who have sex with men (MSM) in four U.S. metropolitan areas, and includes both HIV-infected (HIV+) and HIV-seronegative (HIV-) men. In the MACS, the number of CVD events is relatively low;therefore, to study this question, we have conducted a subclinical CVD study including coronary artery calcium (CAC) by CT scanning and carotid intima media thickness (IMT) and plaque by ultrasound. The initial cross sectional analyses are equivocal. These tests are now being repeated in the same men to evaluate short-term (3-year) longitudinal changes in these parameters of subclinical CVD. These equivocal results suggest that further study with more sensitive and specific imaging modalities, and/or longer follow-up of people treated with HAART, are necessary to examine potential associations between HIV infection and/or HAART and CVD and to identify factors associated with subclinical and ultimately clinical CVD. Both improved imaging and longer follow-up can be accomplished by continuing and extending the CVD studies begun in the MACS. Therefore, the specific aims of this application are: 1) to determine whether there is a difference in the a) prevalence and b) progression of subclinical CVD between HIV+ and HIV- men;and 2) to determine whether metabolic, inflammatory, immunologic and anthropomorphic markers potentially associated with HAART and/or HIV infection are associated with presence and/or progression of subclinical CVD, thus identifying potential mechanisms leading to subclinical CVD in this population. To address these aims, we will obtain the following studies in HIV+ and HIV- men (1) CT angiographic imaging of the coronary arteries (CTA), a novel technology that can visualize calcified as well as non-calcified atherosclerotic plaque, (2) measures of inflammatory, immunologic, metabolic, and anthropomorphic parameters with blood assays and CT imaging and (3) longitudinal changes in CAC and carotid IMT to build on the existing data that have been obtained in the MACS CVD substudy. Since HIV disease is associated with myocardial dysfunction we will characterize the prevalence and risk factors for left ventricular systolic dysfunction. An important strength of the MACS is the inclusion of a control group of HIV- men of similar demographics and HIV risk behaviors as HIV+ men. These men have been followed longitudinally with the same MACS protocol, thus allowing a comparison to the underlying population. As the number of people treated with HAART continues to rise, the need to further refine our understanding of any potential CVD risks becomes critical. The proposed studies will lead to an increased understanding of vascular and myocardial disease in HIV infection and potential mechanisms leading to subclinical CVD which can later be used to develop effective CVD prevention strategies in this population.

Public Health Relevance

There is controversy regarding the degree to which HIV infection, highly active antiretroviral therapy (HAART), or immune suppression contribute to the risk of CVD. This study will use novel imaging technology to measure subclinical vascular and myocardial disease and examine mechanisms for increased risk in HIV- infected compared with HIV-seronegative men. Results can be used to target prevention strategies.

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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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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Kelly, Sean G; Plankey, Michael; Post, Wendy S et al. (2016) Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study. PLoS One 11:e0147822
Rezaeian, Panteha; Miller, P Elliott; Haberlen, Sabina A et al. (2016) Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study. J Cardiovasc Comput Tomogr 10:229-36
Hanna, David B; Guo, Mengye; Bůžková, Petra et al. (2016) HIV Infection and Carotid Artery Intima-media Thickness: Pooled Analyses Across 5 Cohorts of the NHLBI HIV-CVD Collaborative. Clin Infect Dis 63:249-56
Monroe, Anne K; Haberlen, Sabina A; Post, Wendy S et al. (2016) Cardiovascular disease risk scores' relationship to subclinical cardiovascular disease among HIV-infected and HIV-uninfected men. AIDS 30:2075-84
Brener, Michael I; Post, Wendy S; Haberlen, Sabina A et al. (2016) Comparison of Insulin Resistance to Coronary Atherosclerosis in Human Immunodeficiency Virus Infected and Uninfected Men (from the Multicenter AIDS Cohort Study). Am J Cardiol 117:993-1000
Thomas, Guajira P; Li, Xiuhong; Post, Wendy S et al. (2016) Associations between antiretroviral use and subclinical coronary atherosclerosis. AIDS 30:2477-2486
Palella Jr, Frank J; McKibben, Rebeccah; Post, Wendy S et al. (2016) Anatomic Fat Depots and Coronary Plaque Among Human Immunodeficiency Virus-Infected and Uninfected Men in the Multicenter AIDS Cohort Study. Open Forum Infect Dis 3:ofw098
McKibben, Rebeccah A; Haberlen, Sabina A; Post, Wendy S et al. (2016) A Cross-sectional Study of the Association Between Chronic Hepatitis C Virus Infection and Subclinical Coronary Atherosclerosis Among Participants in the Multicenter AIDS Cohort Study. J Infect Dis 213:257-65
Monroe, Anne K; Brown, Todd T; Cox, Christopher et al. (2015) Physical Activity and Its Association with Insulin Resistance in Multicenter AIDS Cohort Study Men. AIDS Res Hum Retroviruses 31:1250-6
Miller, P Elliott; Haberlen, Sabina A; Metkus, Thomas et al. (2015) HIV and coronary arterial remodeling from the Multicenter AIDS Cohort Study (MACS). Atherosclerosis 241:716-22

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