HIV-associated Myocardial Diastolic Dysfunction: A Prospective Cohort Study

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PROJECT SUMMARY / ABSTRACT Candidate: Dr. Justin Kingery is board certified in Internal Medicine and holds a PhD in cardiovascular physiology and immunology. Training in Tanzania as a global health fellow for the past four years, he has developed collaborations with Tanzanian scientists, trained a local study team, and authored six publications. Dr. Kingery’s work has focused on the role of monocytes in myocardial dysfunction and the epidemiology of HIV-associated heart disease in Tanzania, both of which form the basis for the proposed research training. Career Development Plan: Dr. Kingery’s long-term goal is to become an independent physician scientist dedicated to clinical research in the prevention and treatment of cardiovascular disease in HIV-infected patients. Objectives during this K23 award include: 1) to gain expertise in clinical epidemiology through coursework and enrollment of a clinical cohort under the mentorship of Drs. Fitzgerald, Kapiga and Devereux. 2) To increase biostatistics skills through courses and analysis of his own data mentored by Dr. Martin Wells. 3) To increase understanding of HIV virology, immunology, and HIV-induced inflammation through courses, conferences, and mentored research under Drs. Fitzgerald, Kapiga and Koretzky. 4) To transition to an independent patient-oriented investigator and strengthen leadership skills through coursework at Weill Cornell Medicine on grant writing, workshops on mentorship and submission of a R01 application in grant Year 4. Environment: The proposed research and training will take place at the Weill Bugando School of Medicine HIV Clinic (Tanzania), the Mwanza Intervention Trials Unit (Tanzania) and Weill Cornell Medicine (USA). The partnership between these institutions provides a unique collaborative environment with the infrastructure for both large clinical studies and translational research. These institutions are committed Dr. Kingery’s career. Research: The proposed research builds upon Dr. Kingery’s prior work in Tanzania. In Aim 1, he will conduct a prospective cohort study to determine the incidence and predictors of diastolic dysfunction in 500 HIV-infected and 500 uninfected adults in Tanzania. He hypothesize that the incidence of new-onset diastolic dysfunction will be ≥ 2-times higher in HIV-infected adults than in HIV-uninfected controls and preceded by elevated innate immune factor sST2. He will also determine the contributions of traditional risk factors (age, hypertension, obesity, and diabetes) and HIV-specific factors (antiretroviral drugs, nadir CD4 count, and viral loads). In Aim 2, he will conduct a nested case control study within the Aim 1 cohort to determine the temporal relationship between peripheral blood monocyte phenotype and incident diastolic dysfunction in four groups of 25 each of HIV-infected and uninfected adults with and without diastolic dysfunction. He hypothesize that the ratio of peripheral blood alternatively activated monocytes (AAM)/classically activated monocytes (CAM) will be ≥ 2.5 times higher in HIV-infected adults and that an increased AAM/CAM ratio will precede and predict incident diastolic dysfunction.