In older adults, chronic inflammation is an independent risk factor for poor physical function, muscle weakness, cardiovascular disease, and mortality. Similarly, increased levels of biomarkers of inflammation in HIV-infected adults independently predict cardiovascular disease and death, regardless of immune status. HIV-infected adults have increased risk for poor aerobic capacity, muscle weakness and sarcopenia, all of which may be accelerated by chronic inflammation. Yet, the impact of chronic inflammation on these outcomes and the effect of exercise training is not well understood. In HIV negative adults with diastolic dysfunction, biomarkers of inflammation and cardiac fibrosis predict cardiac function and mortality. In elderly HIV negative adults with diastolic dysfunction, aerobic exercise training increases aerobic capacity 16%. HIV-infected adults have a 4- fold increased risk of diastolic dysfunction. Our preliminary data indicates that diastolic dysfunction is associated with poor aerobic capacity in asymptomatic HIV-infected veterans. Exercise rehabilitation studies in younger HIV-infected adults, based on American College of Sports Medicine (ACSM) recommendations, show improvements in aerobic capacity, muscle weakness and sarcopenia but limited data are available in older HIV-infected adults. Our preliminary data shows that high-intensity aerobic exercise training in older HIV- infected adults is well tolerated and increases aerobic capacity by 17%. The effects on diastolic function, and correlates of systemic inflammation and cardiac fibrosis, are unknown in this population. The objective of this study is to determine the effect o exercise training on the central (cardiovascular) and peripheral (muscular) impairments underlying poor physical function by comparing older HIV-infected veterans randomized to combined aerobic and resistance exercise training versus usual care. Our hypothesis is that a progressive aerobic and resistance rehabilitation program will increase aerobic capacity and muscle strength, which will be mediated by improved diastolic function, increased muscle mass, and decreased systemic inflammation. To test this hypothesis, we will conduct a randomized 16-week trial of progressive aerobic and resistance training versus usual care control in 60 sedentary older (50+ years) HIV- infected veterans. We will determine the effects of exercise training on aerobic capacity and diastolic function, and their relationship to changes in biomarkers of systemic inflammation and cardiac fibrosis (AIM 1). We will also determine the effect of exercise training on strength and muscle mass, and their relationship to changes in biomarkers of systemic inflammation (AIM 2). The VA is the largest health care provider for HIV-infected individuals in the United States with over 25,000 patients, of which 64% are over 50 years of age. Findings from this novel translational research will provide the foundation for future mechanistic research to investigate organ-specific effects of exercise training, including cardiac remodeling and fibrosis, and skeletal muscle expression of inflammatory cytokines. Collectively, the proposed research will advance our goal to develop effective rehabilitation strategies that improve the health and functional independence of HIV-infected veterans.

Public Health Relevance

Research is needed to determine safe and effective exercise rehabilitation programs to prevent and improve physical disability in older adults living with HIV. This problem is of great importance to the VA. The majority of the 25 thousand HIV-infected veterans are over 50 years of age (64%). The combined effect of aging and inflammation increase the risk for physical disability in older HIV-infected veterans. This translational exercise training trial will examine he cardiac and skeletal muscle effects of combined aerobic exercise and resistance training to attenuate the functional declines of aging with HIV by reducing the deleterious consequences of chronic inflammation. Findings will guide future rehabilitation research on cardiac remodeling and inflammation of skeletal muscle. The proposed research will advance the goal to develop effective rehabilitation strategies that improve the health of older HIV-infected veterans.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX000667-02
Application #
8990397
Study Section
Musculoskeletal/Orthopedic Rehabilitation (RRD2)
Project Start
2014-04-01
Project End
2018-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Baltimore VA Medical Center
Department
Type
DUNS #
796532609
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Nieves-Lugo, Karen; Del Rio-Gonzalez, Ana Maria; Reisen, Carol et al. (2017) Greater Depressive Symptoms and Higher Viral Load Are Associated with Poor Physical Function among Latino Men Living with HIV. J Int Assoc Provid AIDS Care 16:30-36
Freiberg, Matthew S; Chang, Chung-Chou H; Skanderson, Melissa et al. (2017) Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol 2:536-546
Akgün, Kathleen M; Tate, Janet P; Oursler, Krisann K et al. (2016) Association of chronic obstructive pulmonary disease with frailty measurements in HIV-infected and uninfected Veterans. AIDS 30:2185-93
Ortmeyer, Heidi K; Ryan, Alice S; Hafer-Macko, Charlene et al. (2016) Skeletal muscle cellular metabolism in older HIV-infected men. Physiol Rep 4:
Oursler, Kris Ann; Sorkin, John David (2016) HIV and Aging. Int J Infect Dis 53:59-60
Althoff, Keri N; McGinnis, Kathleen A; Wyatt, Christina M et al. (2015) Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis 60:627-38
Akgün, Kathleen M; Tate, Janet P; Crothers, Kristina et al. (2014) An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals. J Acquir Immune Defic Syndr 67:397-404
Armah, Kaku A; Chang, Chung-Chou H; Baker, Jason V et al. (2014) Prehypertension, hypertension, and the risk of acute myocardial infarction in HIV-infected and -uninfected veterans. Clin Infect Dis 58:121-9
So-Armah, Kaku A; Chang, Joyce; Alcorn, Charles et al. (2014) HIV infection, antiretroviral therapy initiation and longitudinal changes in biomarkers of organ function. Curr HIV Res 12:50-9
Oursler, Krisann K; Tate, Janet P; Gill, Thomas M et al. (2013) Association of the veterans aging cohort study index with exercise capacity in HIV-infected adults. AIDS Res Hum Retroviruses 29:1218-23

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