Exercise for Healthy Aging: The Impact of HIV and Aging on Physical Function and the Somatopause

The primary objective of this proposal is to compare a moderate or high intensity exercise intervention to improve physical function in persons aging with HIV. Both HIV-infected and HIV-uninfected older adults will be assigned to a moderate intensity cardiovascular and resistance training intervention for 12 weeks, and then randomized to either continue moderate intensity exercise, or increase to high intensity exercise for an additional 12 weeks. The primary outcome is the impact of exercise on physical function, as measured by the overall score of a modified Short Physical Performance Battery (mSPPB) and the chair rise time from the mSPPB. The secondary outcomes include changes in insulin-like growth factor-1 (systemic and local) and inflammation (interleukin-6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2)).

Inclusion criteria

• Ages 50-75
• HIV+ must be on ART for a minimum of 2 years with viral load <200 copies/mL
• Sedentary
• cluster of differentiation 4 (CD4) T-cell count >200 cells/microliter
• BMI >19 and <41
• Among females, must be post-menopausal
• Able to perform activities of daily living with out assistance

Exclusion criteria

• Diabetes, poorly controlled with HgbA1c >7.5; on insulin
• On growth hormone (or growth hormone axis) therapy, intramuscular testosterone, corticosteroids.
• Known active hepatitis B or C (viremia).
• Severe liver disease
• Uncontrolled hypertension (SPB >180 or diastolic >100).
• Underlying cardiac conditions that would make exercise or exercise testing potentially unsafe (unstable ischemic heart disease, Class III or IV heart failure clinically significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia)
• pulmonary disease requiring the use of supplemental oxygen ≥ 4 liters with physical exertion
• current diagnosis of malignancy (excluding non-melanoma skin cancers) within 48 weeks prior to enrollment
• surgery/trauma/injury/fracture within 24 weeks prior to enrollment that may impact a subject's ability to exercise
• history of stroke with residual deficits that may impact ability to exercise; orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly limit the ability to perform moderate-intensity resistance exercise (e.g., unable to be properly positioned in exercise equipment or to have severely restricted range of motion even after modifications have been made)
• weight over 300 pounds
• Montreal Cognitive Assessment (MOCA) score < 18 (will be evaluated at screening visit after consent obtained)
• AIDS-defining opportunistic infection within the 24 weeks prior to enrollment
• Person who appear to have unstable health, are incapable of safely participating in the exercise intervention, or are felt to have a life expectancy of < 1 year.
• Participants on anticoagulants (clopidogrel, Coumadin, etc) will be excluded from the muscle biopsy.
• Aspirin and Non-steroidal anti-inflammatory agents are not exclusions but should be stopped 1 week prior to muscle biopsy (subset of subjects).