Half of those living with HIV in the U.S. are or will soon be >50 years of age. Heart failure, which has one of the highest disease burdens of any age-related condition nationwide, may soon become the most costly HIV- related comorbidity in terms of premature mortality, suffering, and healthcare expenditures. Many of its known risk factors are common to HIV-infected and uninfected individuals alike, but less is known about its pathogenesis in the context of suppressive HIV therapy. New evidence suggests that long-term survival with HIV is associated with greater risks for systolic and diastolic dysfunction as well as resultant heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Against a background of high diabetes, hypertension, and obesity risk in minority groups affected disproportionately by HIV, a unique set of etiologic and prognostic factors for heart failure in the context of HIV infection likely exists. The proposed research is a set of epidemiologic studies characterizing the role of HIV infection in heart failure incidence and survival, based on data from the largest HIV care provider in the Bronx, NY.
Aim 1 will assess the association between HIV infection and heart failure incidence, and Aim 1b will identify risk factors, including major comorbidities, that may lead to greater mortality in optimally treated HIV-infected heart failure patients compared with HIV-uninfected heart failure patients.
Aims 2 and 3 will implement machine learning methods within our longitudinal electronic medical record database to construct prediction models identifying HIV+ patients at greatest risk of developing HF, and to identify unique HIV-specific phenotypes of HFpEF and HFrEF. Prediction models developed in our clinical population (90% minority, 40% female) will be validated in a demographically complementary HIV+ cohort in Chicago (50% minority, 15% female) to evaluate the transportability of these models across patient populations. This award will provide ample training opportunities for the candidate to continue his progression to an independent academic research career with specialized experience at the intersection of HIV, cardiovascular disease, and medical informatics. Established institutional resources and a mentoring team with a proven record of success, as well as research conducted within a geographic area with endemic levels of HIV and heart disease, provide an ideal setting to successfully produce high quality research with major impact. The collaboration will establish a program for large-scale translational research in HIV and heart failure by developing a shared research platform between two major research institutions in the Bronx and Chicago.

Public Health Relevance

Heart failure imposes one of the highest disease burdens of any condition in the U.S., with over 6 million Americans affected, and costs reaching $34 billion annually. The extent to which it affects people living with HIV is currently unclear but of critical importance, due to the aging of the population as a result of successful antiretroviral therapy. Our work will allow for the prediction of heart failure risk in people living with HIV and identify unique heart failure phenotypes in the context of HIV infection, both of which may help to tailor prevention and treatment efforts in the future in this vulnerable population.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
6K01HL137557-04
Application #
9858825
Study Section
NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
Program Officer
Hsu, Lucy L
Project Start
2017-04-01
Project End
2020-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
081266487
City
Bronx
State
NY
Country
United States
Zip Code
10461
Glesby, Marshall J; Hanna, David B; Hoover, Donald R et al. (2018) Abdominal fat depots, insulin resistance, and incident diabetes mellitus in women with and without HIV infection. AIDS 32:1643-1650
Huck, Daniel M; Hanna, David B; Rubin, Leah H et al. (2018) Carotid Artery Stiffness and Cognitive Decline Among Women With or at Risk for HIV Infection. J Acquir Immune Defic Syndr 78:338-347
Kimura, Takayuki; Kobiyama, Kouji; Winkels, Holger et al. (2018) Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B. Circulation 138:1130-1143
Moran, Caitlin A; Sheth, Anandi N; Mehta, C Christina et al. (2018) The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women. AIDS 32:999-1006
Glesby, Marshall J; Hanna, David B; Hoover, Donald R et al. (2018) Abdominal Fat Depots and Subclinical Carotid Artery Atherosclerosis in Women With and Without HIV Infection. J Acquir Immune Defic Syndr 77:308-316
Shan, Zhilei; Clish, Clary B; Hua, Simin et al. (2018) Gut Microbial-Related Choline Metabolite Trimethylamine-N-Oxide Is Associated With Progression of Carotid Artery Atherosclerosis in HIV Infection. J Infect Dis 218:1474-1479
Dara, Jasmeen S; Hanna, David B; Anastos, Kathryn et al. (2018) Low Birth Weight in Human Immunodeficiency Virus-Exposed Uninfected Infants in Bronx, New York. J Pediatric Infect Dis Soc 7:e24-e29
Hanna, David B; Moon, Jee-Young; Haberlen, Sabina A et al. (2018) Carotid artery atherosclerosis is associated with mortality in HIV-positive women and men. AIDS 32:2393-2403
Qi, Qibin; Hua, Simin; Clish, Clary B et al. (2018) Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis. Clin Infect Dis 67:235-242
Ross, Jonathan; Cunningham, Chinazo O; Hanna, David B (2018) HIV outcomes among migrants from low-income and middle-income countries living in high-income countries: a review of recent evidence. Curr Opin Infect Dis 31:25-32

Showing the most recent 10 out of 11 publications