Low Cardiorespiratory Fitness and Chronotropic Incompetence inHIV: Risk Factors, Cardiovascular Implications, and Exercise Training as Treatment

ABSTRACT This is a K23 Patient-Oriented Mentored Career Development award for Dr. Matthew Durstenfeld. His proposed research focuses on cardiorespiratory fitness and chronotropic incompetence and their implications for cardiovascular disease among people with human immunodeficiency virus (HIV). Candidate: Dr. Durstenfeld is a board-certified internist and cardiologist and an Assistant Professor of Medicine at the University of California, San Francisco, in the UCSF Division of Cardiology at Zuckerberg San Francisco General. He seeks research training at the interface of cardiology and infectious diseases. Training: Through hands-on, mentored patient-oriented research, formal didactics and seminars, and other activities, Dr. Durstenfeld’s career development plan is designed to prepare him for a career as an independent investigator in the field of infection-associated cardiovascular disease. Dr. Durstenfeld’s goals are to: (1) Strengthen his ability to conduct and analyze longitudinal cohorts, (2) Gain content expertise in (a) HIV- associated immune activation and inflammation, (b) advanced cardiac imaging, and (c) exercise in HIV, and (3) Prepare to lead clinical trials to improve cardiovascular health for diverse populations. Mentors/Environment: Dr. Durstenfeld’s team of mentors at UCSF is led by Dr. Priscilla Hsue, a groundbreaking pioneer in HIV cardiology. Co-mentors include Dr. Steve Deeks (HIV, clinical research), Dr. John Kornak (biostatistics), and Dr. Alexis Beatty (methods, exercise, and cardiovascular monitoring), and Dr. Kristine Erlandson (Exercise in HIV). Advisors include Dr. Ahmed Tawakol (FDG PET/CT) and Dr. Michael Lu (Coronary CTA). UCSF is an exceptional environment for early-stage investigators and clinical research, especially at Dr. Durstenfeld’s focus interface of cardiology and HIV, with resources including the Clinical and Translational Science Institute, Center of Vascular Excellence, and UCSF Bay Area Center for AIDS Research. Research: Low cardiorespiratory fitness (CRF) and chronotropic incompetence (CI), the inability to increase heart rate adequately during exercise, may be underrecognized and treatable contributors to cardiovascular disease, especially among people with HIV. Leveraging three NIH-funded clinical trials, the first aim is to describe patterns and risk factors for low CRF and CI in HIV and longitudinal effects of CI on CRF. Leveraging measurements conducted in two NIH-funded clinical trials, the second aim is to identify associations of low CRF and CI with subclinical cardiovascular disease. The third aim is to conduct a proof-of-concept, randomized controlled trial of exercise training for HIV-associated chronotropic incompetence. Summary: These foundational studies will lead to a greater understanding of the role of CRF and CI in cardiovascular disease among people with HIV. Anchored by an experienced, multidisciplinary, collaborative mentoring team and formal career development activities, Dr. Durstenfeld’s career development plan will facilitate his development into an independent investigator and leader in infectious-disease cardiology.