People who are infected with HIV, especially those on long-term antiretroviral therapy (ART) or who use cocaine, have a high prevalence of LV dysfunction. Since ART use could lead to diabetes, and since cardiac steatosis (fatty heart) has been identified in those with diabetes, it is critical to examine whether HIV infection, ART use, and cocaine use promote cardiac steatosis, a marker for cardiomyopathy. Virtually no reported studies have addressed the combined effects of HIV infection, ART use, and cocaine use on the etiology of cardiomyopathy. According to our preliminary study, cardiac steatosis is prevalent in HIV-infected individuals, especially those on ART. These results are entirely new and never before reported. This application seeks support for conducting novel research on the effects of HIV infection, ART use, and cocaine use on cardiac steatosis. The proposed study, using the cohort of study participants enrolled in the ongoing study DA12777, will employ magnetic resonance imaging (MRI) to accurately quantify the ectopic fat deposition in the myocardium and will explore the association between HIV infection, ART use, cocaine use, and cardiac steatosis. The proposed specific aims of this study are (1) To estimate the prevalence and incidence of cardiac steatosis and left ventricular (LV) dysfunction in cardiovascularly asymptomatic men and women with one of the following characteristics: HIV(-) and cocaine(-);HIV(-) and cocaine(+);HIV(+) and cocaine(-) and ART(-);HIV(+) and cocaine(-) and ART(+);HIV(+) and cocaine(+) and ART(-);and HIV(+) and cocaine(+) and ART(+);(2) To examine the effects of HIV infection on the presence and development of cardiac steatosis and regional LV dysfunction;(3) To examine the effects of the various classes of ART and individual ART on the presence and development of cardiac steatosis and regional LV dysfunction in HIV-infected persons;(4) To examine the effects of cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction;(5) To examine the joint effects of HIV infection, ART use, and cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction;and (6) To investigate the direct effects and mechanisms of HIV infection, ART use, and cocaine use on mitochondrial damage. This study will be among the first, if not the very first, to explore the mechanisms of premature HIV/cocaine-related cardiomyopathy, and its findings may lead to a breakthrough in research on prevention/intervention related to heart failure in HIV-infected persons and to translation of scientific discoveries into clinical applications.

Public Health Relevance

This study will investigate why HIV-infected African Americans have high rates of cardiac steatosis and regional left ventricular dysfunction. The study could provide critical information for understanding the mechanisms of premature heart failure and lead to a breakthrough in research on prevention/intervention of heart disease in HIV-infected persons and to translation of scientific discoveries into clinical applications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012777-15
Application #
8507678
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Khalsa, Jagjitsingh H
Project Start
1999-06-15
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
15
Fiscal Year
2013
Total Cost
$631,783
Indirect Cost
$194,814
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Lai, Shenghan; Gerstenblith, Gary; Li, Ji et al. (2015) Chronic cocaine use and its association with myocardial steatosis evaluated by 1H magnetic resonance spectroscopy in African Americans. J Addict Med 9:31-9
Liu, Chia-Ying; Bluemke, David A; Gerstenblith, Gary et al. (2014) Myocardial steatosis and its association with obesity and regional ventricular dysfunction: evaluated by magnetic resonance tagging and 1H spectroscopy in healthy African Americans. Int J Cardiol 172:381-7
Liu, Chia-Ying; Bluemke, David A; Gerstenblith, Gary et al. (2014) Reference values of myocardial structure, function, and tissue composition by cardiac magnetic resonance in healthy African-Americans at 3T and their relations to serologic and cardiovascular risk factors. Am J Cardiol 114:789-95
Lai, Hong; Fishman, Elliot K; Gerstenblith, Gary et al. (2013) Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk. Vasc Health Risk Manag 9:729-37
Lai, Shenghan; Fishman, Elliot K; Gerstenblith, Gary et al. (2013) Vitamin D deficiency is associated with coronary artery calcification in cardiovascularly asymptomatic African Americans with HIV infection. Vasc Health Risk Manag 9:493-500
Lai, Hong; Detrick, Barbara; Fishman, Elliot K et al. (2012) Vitamin D deficiency is associated with the development of subclinical coronary artery disease in African Americans with HIV infection: a preliminary study. J Investig Med 60:801-7
Lai, Hong; Gerstenblith, Gary; Fishman, Elliot K et al. (2012) Vitamin D deficiency is associated with silent coronary artery disease in cardiovascularly asymptomatic African Americans with HIV infection. Clin Infect Dis 54:1747-55
Du, Jiefu; Wasserman, Bruce A; Tong, Weijing et al. (2012) Cholesterol is associated with the presence of a lipid core in carotid plaque of asymptomatic, young-to-middle-aged African Americans with and without HIV infection and cocaine use residing in inner-city Baltimore, Md., USA. Cerebrovasc Dis 33:295-301
Detrick, Barbara; Hooks, John J (2010) Immune regulation in the retina. Immunol Res 47:153-61
Lai, Hong; Zeng, Huiyang; Zhang, Cheng et al. (2009) Toxic effect of methamphetamine on the retina of CD1 mice. Curr Eye Res 34:785-90

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