Exercise Training to Improve Brain Health in Older HIV+ Individuals

Management of older persons living with HIV (PLWH) (≥ 50 years old) is becoming increasingly
more complex as a majority is greater than 50 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.

Inclusion Criteria:

1. age > 50 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 regularly 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