Functional Interval Training for Veterans Exercising Through Telehealth.

The Veterans Health Administration (VHA) is the largest U.S. HIV health provider with 64% of these Veterans 50+ years of age. HIV infection in the setting of antiretroviral therapy represents a chronic disease with an advanced aging phenotype manifested as increased cardiovascular disease, sarcopenia, and frailty, primarily driven by systemic inflammation. The investigators found a 42% reduction in VO2peak in older HIV+ adults that significantly improved with high-intensity aerobic (AEX) and resistance training (RT). Yet, durable strategies for high-intensity exercise in older adults remain a challenge and limited data are available in older HIV+ adults. There is an urgent need to address these knowledge gaps in order to prevent widespread disability in HIV+ Veterans. The objective is to provide a high-intensity exercise program for older Veterans that can be widely disseminated and attenuates processes underlying aging. Epigenetic changes with increased age encapsulate the putative effects of biological aging and lifestyle factors. DNA methylation (DNAm) patterns are frequently modified in genes encoding pro-inflammatory cytokines, but can be reversed with exercise training. DNA methylation age (DNAm Age) is an epigenetic biomarker that is expressed in years and provides a concrete benchmark of advanced aging. The investigators found that HIV+ adults have DNAm Age 11 years greater than age-matched adults without HIV. Further, in adults without HIV, increased DNAm Age is associated with physical inactivity, weakness and frailty. Preliminary data in the Veterans Aging Cohort Study (VACS) show that DNAm Age correlates with the VACS Index, a measure of frailty in HIV+ adults. However, the impact of exercise training on DNAm Age has yet to be determined in any patient population. The investigators propose to adapt center-based high-intensity AEX+RT intervention in older HIV+ Veterans into a video telehealth (VTEL) delivered functional (no stationary equipment) exercise program that leverages epigenetic outcomes to demonstrate anti-aging effects of exercise. The overarching hypothesis is that VTEL high-intensity functional circuit exercise in older HIV+ Veterans will improve the advanced aging phenotype and attenuate DNAm epigenetic processes underlying aging. Experimental approach includes a 12-week VTEL exercise intervention in 80 older HIV+ Veterans who are randomized to exercise or standard of care sedentary control groups. AIM 1 will determine the effect of VTEL exercise on VO2peak, sarcopenia, and frailty as phenotypic outcomes of advanced aging in HIV. AIM 2 will investigate the effect of VTEL exercise on DNAm Age as a biomarker of advanced aging. AIM 3 will determine the effect of VTEL exercise on DNA methylation of specific genes encoding specific pro-inflammatory cytokines in leukocytes. This approach will advance an understanding of effective and feasible exercise strategies to prevent and minimize disability in patient populations with advanced aging. Findings will provide an innovative approach to functional exercise in all older adults. DNAm Age could be used as a personalized benchmark for an individual's benefit from exercise to promote sustainable behavior change. Findings will also provide epigenetic risk profiles that can be used to generate a personalized exercise prescription, an important next step in the next decade of precision medicine. The proposal leverages exercise training experience in HIV and VTEL, availability of 3,000 HIV+ Veterans at Atlanta and Baltimore VAMCs, and the VHA VTEL infrastructure. The capacity to disseminate VTEL exercise with minimal cost using existing infrastructure will facilitate large-scale dissemination and national impact. Deliverables include improved clinical outcomes and substantial cost savings from reduced hospitalization and institutionalization rates.

Inclusion criteria

• Veteran living with HIV and under care at VAMC
• 50 years of age and older
• Stable antiretroviral therapy (same ARV medications within 3 months)
• At least one HIV-1 PCR < 20 c/ml (viral load) within prior 6 months

Exclusion criteria

• History of AIDS defining illnesses (within 6 months; CDC Criteria)
• Myocardial infarction (within 3 months)
• Exertional or unstable angina (current chest pain that limits activity)
• Severe congestive heart failure (EF < 20% in last year or NYHA Classification III or IV)
• Uncontrolled hypertension (SBP >180 &/or DBP > 110 mm Hg)
• Therapy with beta blockers or non-dihydropyridine calcium channel blocker (within 1 month)
• Screening EKG with ischemia, complex arrhythmia, or high-grade block (per Minnesota Code)
• Poorly controlled DM within prior 1 month (FBS>180 mg/dl, RBS > 299 mg/dl, or HbA1C > 10)
• Receiving treatment for cancer except skin cancer (within 3 months)
• Peripheral vascular disease with claudication
• Severe arthritis limiting ambulation
• Neurologic disease limiting ambulation (requiring assist device)
• End stage liver disease (decompensated liver disease)
• Chronic renal failure (requiring dialysis)
• Severe pulmonary disease (home O2, admission for dyspnea or pneumonia within 1 month)
• Use of systemic steroids (testosterone or glucocorticoids) or growth hormone (within 6 months)
• Dementia (based on Evaluation to Consent)
• Signs or symptoms of any medical comorbidity that would preclude exercise testing or training
• Exercise on routine basis (structured aerobic exercise > 3 times per week) within 1 month
• Past medical history of COPD or emphysema AND mMRC score =4