This is a revised application for a K23 Patient-Oriented Mentored Career Development award by Kristine Erlandson, MD. Her proposed research will focus on disturbance in the growth hormone axis as a potential mechanism for physical function decline among human immunodeficiency virus (HIV)-infected adults. Candidate: Dr. Erlandson is a board-certified internist and infectious disease specialist. She is currently an Assistant Professor of Medicine in the Divisions of Infectious Diseases and Geriatric Medicine at the University of Colorado Denver-Anschutz Medical Campus School of Medicine. Dr. Erlandson seeks research training in the disciplines of geriatric medicine, endocrinology/metabolism, and infectious diseases so she can develop the skills needed to investigate complications of aging in HIV infection. Training: Through hands-on mentored research, formal coursework, and conferences/seminars, Dr. Erlandson's K23 career development plan will focus on: 1) developing skills in design and implementation of prospective longitudinal clinical research studies;2) learning to conduct, analyze and interpret studies of th growth hormone axis, including effects of sleep;3) improving knowledge &skills for aging research including conduct of physical function assessments, exercise testing, and muscle biopsies;and 4) strengthening research leadership abilities and expanding research collaborations. Mentors/Environment: Dr. Erlandson has assembled a team of mentors and consultants to bridge the multiple research disciplines necessary to effectively investigate aging in HIV. As mentors, Drs. Campbell, Schwartz, and Brown will provide expertise and career guidance in HIV research (Campbell), aging research (Schwartz), growth hormone and other aspects of endocrinology (Brown, Schwartz), design and conduct of longitudinal clinical trials (Schwartz, Campbell, Brown). Collaborators in sleep (Burgess), statistical analysis of hormone secretion patterns (Carlson), and frequent hormone sampling (Wright) will support Dr. Erlandson in the proposed training and research activities. Additionally, clinical research infrastructure, data management, and statistical support of the AIDS Clinical Trials Group will be available to Dr. Erlandson for the implementation of AIDS Clinical Trials Group-sponsored clinical trials. The stored samples and robust data from HIV-uninfected persons from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study will provide a control group with similar demographic and HIV risk acquisition factors. The University of Colorado will provide research support through the Colorado Clinical and Translational Science Institute (supported by the NIH Clinical Translational Sciences Award), the Graduate School, School of Public Health, numerous opportunities for mentoring, leadership, and teaching, an HIV clinic that provides care for over 1500 patients, a robust multi-disciplinary outpatient Senior's Clinic, and the Hartford Center for Geriatric Excellence. Research: In comparison to similar HIV- populations, HIV+ persons, even when on effective antiretroviral therapy, experience an excess of morbidity and mortality. Persons on ART rarely die from complications of AIDS, but instead have early onset of aging complications including impaired physical function5,16,17, frailty18-22, and falls4. Insulin-like growth factor (IGF)-I is the primary mediator of growth hormone (GH) on muscle and bone. Low IGF-I is associated with frailty, sarcopenia (low muscle mass and strength), and mortality in some aging cohorts. In our cohort of middle-aged HIV+ adults on effective ART, lower IGF-I was associated with a significantly greater odds of functional impairment. Based on our data, we believe impairment in the GH/IGF-I axis may be an important pathway leading to aging complications in HIV. Using five unique, existing cohorts, the proposed project will evaluate the longitudinal association of IGF-I with functional impairment over 144 weeks between HIV+ and HIV- adults (Aim 1);the change in IGF-I with randomized initiation of ART (Aim 2);and the impact of both HIV and age on 24-hour GH secretory patterns (Aim 3). Summary: This will be the first study to evaluate 1) an association of IGF-I with the physical function trajectory among older HIV+ adults, 2) the impact of ART initiation on IGF-I among persons with HIV, and 3) the 24-hour GH secretion patterns in older adults with or without HIV infection. Dr. Erlandson's implementation of this mentored research and training proposal "The Impact of HIV and Aging on Physical Function and the Somatopause," will facilitate her development into an independent investigator and leader in the fields of HIV, successful aging, and physical function.
Aging with HIV may be associated with earlier than expected impairment in physical function. Impaired physical function may result in decreased quality of life, social isolation, nursing home placement, hospitalizations, and ultimately, an increased chance of death. The proposed research will examine the impact of HIV, age, and antiretroviral therapy on growth hormone and insulin-like growth factor-I, and the relationship of these hormones on physical function among people aging with or without HIV infection.