Exercise Training to Improve Brain Health in Older HIV+ Individuals

Management and treatment of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. This proposal will conduct a prospective controlled intervention trial to assess the quantitative and qualitative effects of a monitored aerobic/resistance exercise (EXS) program compared to a social-interaction stretching (SIS) program on brain health (neuropsychological performance testing and neuroimaging measurements) in older PLWH. These results could influence public health policy by encouraging PLWH to adopt a more physically active lifestyle and stimulate the development of effective EXS programs for older PLWH.

Management of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. Attempts to improve the quality of life of older PLWH using adjunctive therapeutics to combination antiretroviral therapy (cART) have largely been unsuccessful.

While the impact of physical activity on brain health (assessed by neuropsychological performance and neuroimaging) has been well studied in older healthy HIV uninfected (HIV-) individuals and neurodegenerative conditions, few studies have concentrated on older PLWH. Both clinically and pathophysiologically, HIV associated neurocognitive disorders (HAND) differs from other neurodegenerative disorders seen with aging (e.g. Alzheimer's disease (AD). A positive association relationship between exercise and cognition has been observed in PLWH, but physical activity has been primarily examined using self-report questionnaires that are subjective and not quantitative. To date, no study has focused on the direct effects of exercise on neuropsychological performance or neuroimaging in PLWH.

The objective of this proposal is to conduct a prospective controlled intervention trial to determine if an increase in physical activity through a monitored aerobic and resistance exercise (EXS) program improves brain health in older PLWH. We will quantify physical function (physical activity using cardiorespiratory capacity and actigraphy) and brain function \[neuropsychological performance testing and neuroimaging (cerebral blood flow (CBF) and brain volume)\] in older physically inactive PLWH at baseline and 26 weeks after randomization to either an EXS or a social-interaction stretching (SIS) program. In addition, we will obtain stool samples, serum markers of neurogenesis, glucose regulation, and systemic inflammation.

A direct impact of these expected outcomes will be the adoption of a more physically active lifestyle by older PLWH and improved EXS guidelines and programs for older PLWH.

Eligibility Criteria:
Inclusion Criteria:

1. age \> 40 years old
2. documented history of HIV infection
3. on stable combination antiretroviral therapy (cART) for approximately 3 months with undetectable plasma HIV RNA
4. physically inactive-sedentary lifestyle (approximately \<2 hours of exercise/week) and not engaged in regular exercise for approximately 3 months prior to enrollment
5. approximately 9 years of education
6. able to have an MRI
7. able to provide written informed consent (does not have LAR, POA, etc.)

Exclusion Criteria:

1. approximately \>2x/week of moderate (or greater) exercise
2. cardiovascular/cerebrovascular disease or pulmonary disease that precludes ability to safely exercise
3. significant neurological disorders (e.g. stroke, head injury with loss of consciousness for \>30 minutes, developmental learning disability
4. presence of dementia or behavioral disorders that would prevent ability to follow the protocol
5. alcohol or substance abuse/ dependence within the last 6 months (DSM-4 TR)
6. contraindications to MRI scanning (e.g. claustrophobia, pacemaker)
7. pregnant or breast-feeding
8. unable to provide written informed consent