Effect of Exercise Training on Inflammation and Function in HIV Infected Veterans

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DESCRIPTION (provided by applicant): 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.