The candidate is an Assistant Professor at the University of Maryland School of Medicine in Division of Infectious Disease and the Institute of Human Virology. The candidate's long-term goal is to become an independent clinical investigator and to contribute to the field of discovery in HIV/AIDS and hepatitis C (HCV). The specific focus is on identifying mechanistic pathways that confer the increased cardiovascular morbidity and mortality with hopes of developing therapeutic targets to reduce the burden of coronary heart disease (CHD) in these patients. The candidate has shown initiative by conducting a longitudinal retrospective cohort study of patients in one of the largest HIV clinics in inner-city Baltimore. Preliminary data demonstrated an association between chronic HCV infection and elevated risk scores for developing CHD in this high-risk population. This result led to the hypothesis for the proposed project as well as another pilot feasibility study evaluating coronary atherosclerosis using coronary CT angiography in these patients. Two manuscripts have been published, and four others are in review related to this work. Rates of CHD are over twice as high in HIV-infected compared to matched uninfected controls, but factors contributing to increased risk of CHD in HIV-infected patients remain to be clearly elucidated. Many studies suggest that HCV co-infection is associated with increased rates of CHD in HIV-infected patients, but results have been mixed. Preliminary data from the candidate?s work suggest that HCV found an association between HCV and CHD in an inner- city, high-risk demographic group and therefore provides strong scientific premise to design a study that will more conclusively delineate this unresolved relationship between HCV and CHD. The goal of this proposal is to establish the extent to which chronic HCV infection increases the burden of CHD in HIV-infected patients, and to elucidate host inflammatory and immune pathways that predict increased CHD burden. We hypothesize that chronic HCV infection in HIV patients increases CHD risk by inducing inflammation and T cell activation that contribute to accelerated progression of CHD. To test our hypothesis, we will use novel non-interferon based therapy to eradicate HCV infection and test whether atherosclerosis decreases, and in doing so, establish a causal link between HCV and atherosclerosis. Identifying predictors of CHD progression from overlapping pathways could inform preventive and therapeutic intervention strategies to mitigate CHD progression in HIV/HCV co-infected patients.

Public Health Relevance

Coronary heart disease (CHD) and HIV will be among the top three causes of mortality worldwide by 2030, and one third of those with HIV are infected with hepatitis C. Rates of heart disease are over twice as high in HIV- infected patients compared to uninfected patients, but the reasons for this remain unclear. We propose to study if hepatitis C increases CHD in HIV patients, if successfully treating hepatitis C will slow progression of CHD, and what host factors might explain the possible synergistic relationship between HIV, hepatitis C, and atherosclerosis in hopes of developing interventions to reduce heart disease in these patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL133358-02
Application #
9492697
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Huang, Li-Shin
Project Start
2017-06-01
Project End
2022-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Alaiti, Mohamad Amer; Goud, Aditya; Ramani, Gautam et al. (2017) Design of the exercise MRI evaluation of HIV-pulmonary arterial hypertension longitudinal determinants (EXALTED) trial. J Cardiovasc Med (Hagerstown) 18:888-896
Bagchi, Shashwatee; Burrowes, Shana Ab; Fantry, Lori E et al. (2017) Factors associated with high cardiovascular risk in a primarily African American, urban HIV-infected population. SAGE Open Med 5:2050312117725644
Babiker, Ahmed; Jeudy, Jean; Kligerman, Seth et al. (2017) Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J Clin Transl Hepatol 5:343-362