HIV
Conditions
Keywords
HIV, AIDS, Cognition, Memory, Exercise, Stretching
Brief summary
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.
Detailed description
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.
Interventions
BEHAVIORALExercise
The resistance exercise training component will follow aerobic exercise and will consist of 4 upper and 3 lower body routines. A combination of guided-motion machines and free weights will be used. Voluntary maximum strength will be measured during the first 4 sessions on each exercise station. The program will initially consist of 1-2 sets of each exercise while lifting a weight that causes muscle fatigue after 8-10 repetitions. The trainer will monitor each participant's exercise response, and when the participant can comfortably lift the weight for 12 repetitions on any exercise, the weight will be increased to cause the muscle group to fatigue after 8 repetitions. This progressive 8-12 repetition cycle is repeated for each exercise over 26 weeks.
BEHAVIORALStretching and Social Interaction
Participants will receive instructions on stretching, range of motion, limbering, and toning. Activities will focus on flexibility enhancement. Along with the stretching and flexibility, this group will have a social interaction component. They will have discussions and interact with trainers and coordinators during all their sessions. These participants will be supervised by the same trainer and will receive the same amount of attention and class interaction as participants in the EXS program.
Sponsors
University of Missouri, St. Louis
University of California, San Diego
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group | 6 months | This measure examines the global z-score which is an average of all the individual cognitive test z scores. We looked at changes in global Z-scores from baseline to follow-up (6 months). A Z-score of 0 represents the population mean. Z-scores are considered to be better when they are above the mean and represent a better outcome. |
| Changes in Brain Structural/Functional Measures in Older PLWH | 26 weeks | The Investigators will assess if an EXS program improves brain structure and function more than a SIS program in older sedentary PLWH. Changes in brain volumetrics (total cortex volume) at baseline (BL) and 26 weeks will be compared between EXS and SIS groups. |
| Change in Level of Daily Activity | 6 Months | Investigators will examine the amount of change in daily activity based on 7-day actigraphy at baseline and then again at follow-up (26 weeks later). Daily activity is measured using an actigraph that participants wear on their wrist and it measures the amount of time spent in sedentary, slightly active, moderately active, vigorously active or very vigorously active categories. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from local clinics as well as a participant registry. Recruitment started in July of 2015 and concluded in November of 2020. There was a pause in recruitment due to the COVID-19 Pandemic from March 2020 through August 2020, and then was terminated early due to a rise in cases in our area in November 2020. A total of 462 were initially screened for the study & 75 were initially enrolled in the study. Out of those 75, a total of 65 were randomized into the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Exercise (EXS) EXS sessions will be at an exercise facility at the WUSTL medical campus. Sessions will be offered weekdays. Sessions will start with range of motion EXS. Participants will follow an individualized EXS training prescription based on baseline cardio testing. Individual aerobic EXS intensity is based on % of maximum HR achieved during the baseline cardiorespiratory fitness test. The target EXS HR will start at 50% and progress to 85% HR reserve. During aerobic EXS, HR will be monitored by a battery-operated monitor. EXS intensity & duration will be increased as the participant acclimates to the EXS prescription. Adaptation is determined when a given EXS intensity yields a lower HR than prior sessions conducted at the same intensity.
Exercise: The resistance EXS training component will follow aerobic exercise and will consist of 4 upper and 3 lower body routines. A combination of guided-motion machines & free weights will be used. Voluntary maximum strength will be measured during the first 4 sessions on each exercise station. The program will initially consist of 1-2 sets of each exercise while lifting a weight that causes muscle fatigue after 8-10 repetitions. The trainer will monitor each participant's EXS response, & when the participant can comfortably lift the weight for 12 repetitions on any exercise, the weight will be increased to cause the muscle group to fatigue after 8 repetitions. This progressive 8-12 repetition cycle is repeated for each exercise over 26 weeks. | 45 |
| Social Interaction Stretching (SIS) This group will serve as a control group against which to gauge the effects of aerobic and resistance training on cognitive function. Participants in this group will follow the same schedule and format as the EXS group. These participants will be supervised by the same trainer and will receive the same amount of attention and class interaction as participants in the EXS program. These SIS participants will receive instructions on stretching, range of motion, limbering, and toning; but the intensity will be far less than that achieved in the EXS classes. Activities will focus on flexibility enhancement. As the participant's level of flexibility increases, stretches with increasing levels of difficulty will be incorporated into the program.
Stretching and Social Interaction: Participants will receive instructions on stretching, range of motion, limbering, and toning. Activities will focus on flexibility enhancement. Along with the stretching and flexibility, this group will have a social interaction component. They will have discussions and interact with trainers and coordinators during all their sessions. These participants will be supervised by the same trainer and will receive the same amount of attention and class interaction as participants in the EXS program. | 20 |
| Total | 65 |
Baseline characteristics
| Characteristic | Exercise (EXS) | Total | Social Interaction Stretching (SIS) |
|---|---|---|---|
| Age, Continuous | 56.5 years | 56.5 years | 56.5 years |
| Body Mass Index | 30.5 kg/m^2 STANDARD_DEVIATION 7 | 29.7 kg/m^2 STANDARD_DEVIATION 6.6 | 28.9 kg/m^2 STANDARD_DEVIATION 5.7 |
| Education | 12.9 years STANDARD_DEVIATION 2.4 | 13.2 years STANDARD_DEVIATION 2.4 | 13.9 years STANDARD_DEVIATION 2.2 |
| Mean duration of HIV infection (in months) (SD) | 225.4 Months of Infection STANDARD_DEVIATION 117.6 | 235.4 Months of Infection STANDARD_DEVIATION 109.7 | 259.0 Months of Infection STANDARD_DEVIATION 94.3 |
| Median CD4 nadir T-cell count (cells/mm3) (IQR) | 195 cells/mm3 | 179.5 cells/mm3 | 47 cells/mm3 |
| Median CD8 T-cell count (cells/mm3) (IQR) | 809 cells/mm3 | 785 cells/mm3 | 689 cells/mm3 |
| Median recent CD4 T-cell count (cells/mm3) (IQR) | 581 cells/mm3 | 578 cells/mm3 | 561 cells/mm3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 43 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 22 Participants | 6 Participants |
| Region of Enrollment United States | 45 participants | 65 participants | 20 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 2 Participants |
| Sex: Female, Male Male | 32 Participants | 50 Participants | 18 Participants |
| Viral Load Undetectable (<50 copies/mL) | 45 Participants | 65 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 20 |
| other Total, other adverse events | 0 / 45 | 0 / 20 |
| serious Total, serious adverse events | 0 / 45 | 0 / 20 |
Outcome results
Primary
Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group
This measure examines the global z-score which is an average of all the individual cognitive test z scores. We looked at changes in global Z-scores from baseline to follow-up (6 months). A Z-score of 0 represents the population mean. Z-scores are considered to be better when they are above the mean and represent a better outcome.
Time frame: 6 months
Population: All participants who completed cognitive testing at baseline and 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise (EXS) | Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group | .10 z-score | Standard Deviation 0.29 |
| Social Interaction Stretching (SIS) | Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group | .20 z-score | Standard Deviation 0.33 |
p-value: 0.3195% CI: [0.05, 0.25]ANOVA
Primary
Change in Level of Daily Activity
Investigators will examine the amount of change in daily activity based on 7-day actigraphy at baseline and then again at follow-up (26 weeks later). Daily activity is measured using an actigraph that participants wear on their wrist and it measures the amount of time spent in sedentary, slightly active, moderately active, vigorously active or very vigorously active categories.
Time frame: 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise (EXS) | Change in Level of Daily Activity | -23.9 Average Minutes per Day | Standard Deviation 114.8 |
| Social Interaction Stretching (SIS) | Change in Level of Daily Activity | -5.3 Average Minutes per Day | Standard Deviation 98.9 |
Comparison: Increases in Time Spent in MVPA and Increased Learning Performance in EXSp-value: 0.005Regression, Linear
Primary
Changes in Brain Structural/Functional Measures in Older PLWH
The Investigators will assess if an EXS program improves brain structure and function more than a SIS program in older sedentary PLWH. Changes in brain volumetrics (total cortex volume) at baseline (BL) and 26 weeks will be compared between EXS and SIS groups.
Time frame: 26 weeks
Population: Participants from both the Exercise and Stretching group's MRIs were analyzed for cortical volume change from pre-intervention to post-intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise (EXS) | Changes in Brain Structural/Functional Measures in Older PLWH | -546.1 mm^3 | Standard Deviation 10358 |
| Social Interaction Stretching (SIS) | Changes in Brain Structural/Functional Measures in Older PLWH | 366.6 mm^3 | Standard Deviation 8102 |
Comparison: Change in Global CBF in EXS vs. SISp-value: 0.24ANOVA
Comparison: Change in Strength \& Change in Frontal Brain Volume in EXSp-value: 0.02Regression, Linear
Comparison: Changes in Brain Volumes associated with changes Memory Performance in EXSp-value: 0.02Regression, Linear