Dr. Hsue is one of the few cardiologists in the world with both extensive research and clinical expertise in HIV and has devoted the last ten years studying cardiovascular disease in the setting of HIV. The initial part of her career was spent 1) establishing a HIV Cardiology Clinic at San Francisco General Hospital (SFGH), 2) developing the infrastructure to perform POR research in the Cardiology Division at SFGH which has included development of a vascular laboratory for clinical research, and 3) performing studies that evaluate the mechanisms underlying HIV infection and cardiovascular disease (CVD). The findings from her work have shown that 1) HIV infection is independently associated with CVD, independent of traditional risk factors or HIV medication, and 2) chronic inflammation in the setting of effectively treated HIV infection underlies this increased CV risk, and 3) identifying therapies to reduce HIV-associated inflammation and CV risk. For her 5 year K24 award proposal, she plans to increase her time spent mentoring junior investigators in the fields of HIV infection, HIV-associated inflammation, and cardiovascular disease for the purpose of helping them to become successful independent researchers in the future. Her K24 proposal will extend upon her current R01 funded investigations by studying the underlying mechanism of HIV-associated atherosclerosis in the setting of treated HIV infection with the following two Specific Aims: 1) To characterize the role of monocyte/macrophage activation in atherosclerotic progression as assessed by carotid artery intima-media thickness (IMT), endothelial dysfunction as assessed by flow-mediated vasodilation of the brachial artery (FMD), and microvascular disease (measured by peak hyperemic velocity) in effectively treated HIV-infected individuals 2) To determine the role of HIV reservoir on atherosclerotic progression, endothelial function, and microvascular disease in effectively treated HIV-infected individuals. The K24 proposal will provide subject visits, vascular imaging, and clinical and laboratory data to support mentoring new investigators in patient-oriented translational research in the field of HIV-related cardiovascular disease.

Public Health Relevance

HIV-infected individuals doing well on therapy now face a higher than expected risk of non-AIDS conditions, including cardiovascular disease for reasons that are not clearly understood. This proposal will help to identify the mechanisms that are associated with this increased risk which can identify novel interventions to reduce risk of health conditions such as cardiovascular disease in HIV as well as other inflammatory conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AI112393-03
Application #
9014491
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Huebner, Robin E
Project Start
2014-03-01
Project End
2019-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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Scherzer, Rebecca; Shah, Sanjiv J; Secemsky, Eric et al. (2018) Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection. Circ Heart Fail 11:e004312
Tawakol, Ahmed; Ishai, Amorina; Li, Danny et al. (2017) Association of Arterial and Lymph Node Inflammation With Distinct Inflammatory Pathways in Human Immunodeficiency Virus Infection. JAMA Cardiol 2:163-171
Phan, Binh An P; Weigel, Bernard; Ma, Yifei et al. (2017) Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis. Circ Cardiovasc Imaging 10:
Crane, Heidi M; Paramsothy, Pathmaja; Drozd, Daniel R et al. (2017) Types of Myocardial Infarction Among Human Immunodeficiency Virus-Infected Individuals in the United States. JAMA Cardiol 2:260-267
Hsue, Priscilla Y; Tawakol, Ahmed (2016) Inflammation and Fibrosis in HIV: Getting to the Heart of the Matter. Circ Cardiovasc Imaging 9:e004427
Sinha, Arjun; Ma, Yifei; Scherzer, Rebecca et al. (2016) Role of T-Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV. J Am Heart Assoc 5:
Kohli, Payal; Ganz, Peter; Ma, Yifei et al. (2016) HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent ""PCSK9-Lipid Paradox"". J Am Heart Assoc 5:
Chow, Felicia C; Boscardin, W John; Mills, Claire et al. (2016) Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals. AIDS 30:45-55
Waters, David D; Hsue, Priscilla Y; Bangalore, Sripal (2016) PCSK9 Inhibitors for Statin Intolerance? JAMA 315:1571-2

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