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AIDS CLINICAL ROUNDS
Brook Henry, Ph.D. Assistant Research Scientist
Department of Psychiatry, University of California, San Diego HIV Neurobehavioral Research Program (HNRP)
AIDS Clinical Rounds October 17, 2014
Physical Activity and Heart Rate Variability in HIV and Methamphetamine Dependence
Physical Activity (PA)
Quality of Life
Cognition Everyday function
Mood
↓Inflammation ↑Cerebral blood flow
Physical fitness
↓ Fat reduction
↑Neurogenesis
PA and HIV PA interventions: aerobic exercise or strength training (Hand, 2009)
Aerobic capacity (V02 max)
Muscle strength Body composition (BMI, lipodystrophy) Metabolic function (cholesterol) Fatigue
Depression Quality of life CD4 count Viral load Inflammation Few studies have examined daily PA in HIV+ and/or compared to HIV- (Fillipas, 2008)
Webel (2014): 1 week diary of exercise activity for 102 HIV+ persons
- Women: 2.4 hours per week - Men: 3.5 hours per week - 24% of sample reported no exercise Excluding walking: - Women: 1.4 hours per week - Men: 1.4 hours per week % of Participants who performed: Walking: 97% Climbing stairs 55% Stretching 39% Lifting Weights 17% Playing Sports 3% Treadmill workouts 4% Pushups 3%
PA and Substance Use Adolescent substance use varies with PA (Terry-McElrath, 2010) PA in adult Methamphetamine (METH) dependence not examined HIV+ injection drug users less active than HIV- drug users (Smit 2006)
Preclinical studies suggest beneficial effects of PA in rodent models (Smith, 2008; Mandyam, 2007; O’Dell, 2011)
8-week aerobic and resistance exercise intervention in METH-
dependent individuals (Dolezal 2013, Mooney 2014)
Heart Rate Variability (HRV) Autonomic nervous system (ANS)
- sympathetic (fight or flight) - parasympathetic (rest and digest) HRV describes the beat- to- beat variations in heart rate
High HRV
Low
High
Heart Rate
Low HRV
Time Stress
Parasympathetic Input (acetylcholine)
Sympathetic Input (norepinephrine)
Amygdala
Prefrontal Cortex
Rostral Ventrolateral Medulla
Nucleus of the solitary tract
Sinoatrial node
Ventricles
Q
R
S
P T
ANS dysfunction common in HIV: - postural hypotension - syncope - constipation, diarrhea, vomiting, urinary incontinence - poor ANS function associated with Veterans Aging Cohort Study (VACS) index (Robinson-Papp, 2013)
Reduced HRV and decreased parasympathetic tone in HIV (Mittal, 2004; Askgaard, 2011; Chow, 2011)
Reduced HRV in METH dependence (Henry, 2012; Dolezal, 2013)
Higher PA linked to improved HRV in healthy and clinical populations (Routledge, 2010; Sandercock, 2005)
HRV and HIV
1) Assess the effect of HIV and METH dependence on PA
2) Assess the effect of HIV and METH on HRV
3) Determine if higher PA improves HRV
4) Determine if higher PA has an effect on neurocognitive impairment (NCI)
Translational Methamphetamine AIDS Research Center (TMARC) Developmental Project: PA and HRV in HIV+ and
METH+ Individuals
METH- METH+
HIV - HIV-/METH- HIV-/METH+
HIV+ HIV+/METH-
HIV+/METH+
HRV Analysis • EQ01 Equivital Life Monitor (Lifestrap)
• 2-lead ECG with 256 Hz sample rate
• Data recorded during 5 minute
rest period
VivoSense software
HRV: Time Domain
SDNN: Standard Deviation of all R-R (or N-N) intervals
RMSSD: Root mean square of successive R-R differences
pNN50: percentage of adjacent R-R intervals that differ by more than 50 milliseconds
HRV: Frequency Domain
Fast Fourier Transformation
Frequency (Hz)
Power (ms2)
Spectral analysis
0.1 0.2 0.3 0.4
Sympathetic + Parasympathetic
0.04 to 0.15 Hz
Parasympathetic 0.15 to 0.4 Hz
LF/HF Ratio: ratio of sympathetic to parasympathetic activity
Low frequency (LF) peak
High frequency (HF) peak
Henry et al., 2009
HRV: Non-linear measures Poincare plot
R-R #1
R-R #2
SD1 SD2
International Physical Activity Questionnaire (IPAQ) • Assessed at 14 sites across 12 countries
• Quantifies 4 types of activity over the past 7 days: - vigorous – aerobics, heavy lifting, digging - moderate – carrying light loads, casual cycling - walking – for at least 10 minutes at a time - sitting – sedentary behavior • Metabolic equivalent (MET) (1 kcal/kg-hr): - vigorous = 8.0 - moderate = 4.0 - walking = 3.3 - rest = 1.0
High 3000+ Met-minutes OR 3 days of vigorous activity, 1500+ Met-min
Moderate
3+ days of 20 min of vigorous activity OR 5+ days of 30 min moderate/walking OR 5+ of any activity, total 600+ Met-min
Low Does not meet above criteria
IPAQ Scoring
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+ n 44 26 35 22 Age 37.1 (2.1) 41.2 (2.3) 38.6 (1.8) 38.4 (1.9) Gender (% male) 75% 85% 86% 95% Education* 14.0 (0.3) 14.3 (0.5) 12.5 (0.3) 12.4 (0.5) Peabody Pic. Vocab 100.4 (1.5) 100.6 (1.7) 95.6 (1.7) 98.4 (2.5) % Caucasian 59% 53% 51% 81% % Smokers 29% 42% 48% 50% BMI 26.8 (0.9) 26.7 (0.7) 28.7 (0.9) 25.1 (0.6) Beck Depression* 3.1 (0.6) 15.5 (2.5) 15.4 (2.0) 16.3 (2.9) Lifetime MDD* 11% 62% 44% 68% Psychotropic use* 11% 42% 20% 41% CD4 current ---------- 503.0 (43.1) ---------- 481.0 (50.5) % AIDS ---------- 38% ---------- 63% Length HIV infection ---------- 96.3 (19.9) ---------- 114.8 (22.2) % Detectable HIV viral load
---------- 65% ---------- 77%
% Current ARV ---------- 57% ---------- 68%
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+ Age first METH use ---------- ---------- 24.7 (1.6) 23.5 (1.4) Length METH abstinence (days)
---------- ---------- 112.1 (22.0) 135.0 (24.3)
Days of METH use ---------- ---------- 1959 (287) 2289 (612) Quantity of METH use (grams)
---------- ---------- 2627 (589) 2718 (1277)
METH use per day (grams)
---------- ---------- 1.2 (0.2) 0.9 (0.2)
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
010203040506070 SDNN
Time Domain Measures
0
10
20
30
40
50
60 RMSSD *
0.00
0.05
0.10
0.15
0.20
0.25
0.30 pNN50 p = 0.08
Frequency Domain Measures
0.000.050.100.150.200.250.300.350.40 HF Power
0.0
1.0
2.0
3.0
4.0
5.0LF/HF Ratio
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
05
10152025303540 SD1
*
Non-linear Measures
0102030405060708090 SD2
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
SDNN RMSSD pNN50 HF LF/HF Ratio
SD1 SD2
Age of first METH use
-0.15 0.02 0.02 0.03 -0.04 0.15 -0.02
Length of METH abstinence
-0.11
-0.14
-0.13
-0.02
-0.11
-0.14
-0.10
METH days of use
-.33* -.29*
-.23*
-.32*
.40*
-.30*
-.33*
Total Quantity of METH use
-0.19
-0.22
-0.18
-0.22
0.15
0.15
0.15
Quantity of METH use per day
0.04
-0.05
-0.11
-0.07
-0.06
-0.05
-0.19
0
20
40
60
80
HIV-METH+ HIV+METH+
SDNN HIV p = 0.05 Days METH**
Time Domain Measures
010203040506070
HIV-METH+ HIV+METH+
RMSSD HIV * Days METH**
0.000.050.100.150.200.250.300.35
HIV-METH+ HIV+METH+
pNN50 HIV * Days METH*
Days of METH use < 1000 n = 12-13 Days of METH use > 1000 n = 10-22
Frequency Domain Measures
0.0
0.1
0.2
0.3
0.4
0.5
HIV-METH+ HIV+METH+
HF Power
0123456
HIV-METH+ HIV+METH+
LF/HF Ratio Days METH p = 0.05
Days of METH use < 1000 n = 12-13 Days of METH use > 1000 n = 10-22
Non-linear Measures
0
10
20
30
40
50
HIV-METH+ HIV+METH+
SD1 HIV * Days METH*
020406080
100120
HIV-METH+ HIV+METH+
SD2 Days METH*
Days of METH use < 1000 n = 12-13 Days of METH use > 1000 n = 10-22
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Unemployed* 34% 46% 71% 68%
Low Activity Occupation*
45% 34% 5% 14%
High Activity Occupation*
11% 12% 20% 14%
Uncertain Activity Occupation
10%
8%
4%
4%
Drives a car 81% 73% 62% 54%
Abnormal Walking gait
2% 4% 3% 5%
Muscle weakness limits activity
0%
4%
0%
5%
Factors that may affect PA
IPAQ Total PA Beta P value
Age -0.05 0.56
Gender -0.04 0.61
Education -0.10 0.28
BMI -0.13 0.15
BDI -0.05 0.53
Drives a car -0.04 0.62
IPAQ Physical Activity
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
050
100150200250300350
Min
utes
Moderate Physical Activity
050
100150200250300350
Min
utes
Vigorous Physical Activity
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
0
200
400
600
800
1000
Min
utes
Walking HIV* HIV x METH p = 0.07
1500
2000
2500
3000
3500
4000
Min
utes
Sitting HIV*
0
200
400
600
800
1000
1200
Min
utes
Total Physical Activity
HIV- METH- HIV+ METH- HIV- METH+ HIV+ METH+
IPAQ PA HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Low 10% 19% 15% 9%
Moderate 23% 35% 31% 41%
High 67% 46%
54% 50%
0
10
20
30
40
50
60
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
RMSSD IPAQ Low/Moderate
IPAQ High
IPAQ Physical Activity and HRV
010203040506070
SDNN
0
10
20
30
40
50RMSSD
0.00
0.05
0.10
0.15
0.20
0.25pNN50
0.000.050.100.150.200.250.300.350.40
HF Power
0
1
2
3
4
5LF/HF Ratio
05
101520253035
SD1
0
20
40
60
80
100SD2
Low/Moderate PA (n = 55) High PA (n = 70)
RMSSD Beta p value
HIV status -0.19 0.03*
METH status -0.09 0.28
Age -0.32 0.00*
IPAQ Sitting -0.19 0.03*
Sedentary behavior and HRV
Low Sitting < 6 hours per day (n = 63) High Sitting > 6 hours per day (n = 62)
010203040506070
SDNN
0
10
20
30
40
50
RMSSD
*
0.00
0.05
0.10
0.15
0.20
0.25pNN50
*
0.000.050.100.150.200.250.300.350.40
HF Power
0.00
1.00
2.00
3.00
4.00
5.00LF/HF Power
05
101520253035
SD1
*
0
20
40
60
80
100SD2
PA and Neurocognitive Impairment
0
10
20
30
40
50
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
% of Participants with NCI
Low/Medium PA (n = 11-16)
High PA (n = 11-30)
Neuropsychological (NP) battery of seven domains (speed of
processing, learning, delayed recall, executive function, verbal fluency, working memory, and motor function). NCI defined as global domain score (GDS) of ≥0.5 (Heaton et al., 2010)
0
200
400
600
800
1000
1200
1400
1600
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Min
utes
Total PA NC Normal (n = 14-24)
NC Impaired (n = 8-11)
p= 0.06
0
50
100
150
200
250
300
350
400
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Min
utes
Vigorous PA NC Normal (n = 14-24)
NC Impaired (n = 8-11)
050
100150200250300350400450500
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Min
utes
Moderate PA
NC Normal (n = 14-24)
NC Impaired (n = 8-11)
0
200
400
600
800
1000
1200
HIV-/METH- HIV+/METH- HIV-/METH+ HIV+/METH+
Min
utes
Walking
NC Normal (n = 14-24)
NC Impaired (n = 8-11)
*
Summary
HRV was decreased in HIV+ participants Lower HRV associated with greater METH use, but no HIV-
METH interaction Total IPAQ PA did not differ across groups, but HIV+ had
less average walking and more sitting Across all groups, more sedentary behavior associated
with lower HRV Less PA was associated with neurocognitive impairment in
HIV+ individuals
iSTEP: A Text Message Physical Activity Intervention to Treat Neurocognitive Deficits in HIV
HIV-associated Neurocognitive Disorders (HAND) Recent work indicates greater PA associated with less NCI in HIV - Exercise in previous 72 hours - Moderate PA reduced odds of NCI in older (50+) HIV+ adults - Longitudinal data for 2-4 visits indicates reduced NC decline (Dufour et al., 2013; Fazeli et al, in submission; Dufour et al, in preparation)
Existing HIV PA intervention studies require fitness and resources (e.g. $, transportation) mHealth interventions used for medication adherence in HIV
iSTEP objective is to develop a personalized PA intervention tailored for HIV+ persons with HAND
iSTEP Aims Aim 1: Assess the efficacy of a 4-month Short Message Service/ Multimedia Message Service (SMS/MMS) intervention on PA.
Hypothesis 1: iSTEP will increase moderate PA compared to baseline. Hypothesis 2: iSTEP will increase moderate PA compared to control. Aim 2: Assess the effect of iSTEP on neurocognition, everyday functioning, and quality of life in HIV+ with HAND Hypothesis 1: iSTEP will improve global cognitive performance compared to control. Hypothesis 2: iSTEP will improvement everyday functioning and quality of life compared to control.
iSTEP Assessment Schedule SCREENING
BASELINE VISIT
FINAL VISIT
4 MONTH INTERVENTION
Phone interview 8 weeks after end of intervention to assess continuing PA and SMS/MMS use
HIV+ HAND+, Medical Consent
Accelerometer for Week 1 PA self-report Neurocognition Everyday functioning Quality of life
Generic Factoid text messages and questions about HIV symptoms and mood Pedometer steps recorded in diary
PHONE INTERVIEW
Control
Intervention
Accelerometer for Week 1 PA self-report Neurocognition Everyday functioning Quality of life
Personalized PA text messages, setting PA goals, reporting step counts via SMS, weekly MMS graphs showing step count progress, participant feedback text questions
Accelerometer for Week 16 PA self-report Neurocognition Everyday functioning Quality of life
Accelerometer for Week 16 PA self-report Neurocognition Everyday functioning Quality of life
Phone interview 8 weeks after end of intervention to assess continuing PA and SMS/MMS use
iSTEP Measures 1) GT3X Accelerometer Counts 2) Omron HJ-321 Pedometer 3) 7-Day Physical Activity Recall (7DPAR) – detailed interview of types
of PA over 7 days
Activity Counts Example Sedentary 0-99 sitting
Light 100-759 Standing, moving slightly
Lifestyle 760-1951 preparing a meal
Moderate 1952-5724 walking
Vigorous 5725-9498 running
Sedentary/Sleep sitting, lying in bed 1 MET
Light standing, deskwork 1.5 MET
Moderate equivalent to walking at normal pace 4 MET
Hard harder than walking, easier than running 6 MET
Very Hard equivalent to running 10 MET
7DPAR Scoring
Total energy expenditure: kcal/kg per week and per day
7DPAR vs. IPAQ
0
200
400
600
800
1000
1200
1400
1600
HIV-/METH-(29)
HIV+/METH-(3)
HIV-/METH+(15)
HIV+/METH+(13)
Min
utes
Total PA
IPAQ
7DPAR
Neurocognitive and Everyday Functioning Assessment
Standard 7 domain NP battery To account for NP practice effects, Z-scores for NP domain variables
will be used to generate a summary regression change score (sRCS). Cysique (2011)
Everyday functioning: Patient's Assessment of Own Functioning (PAOFI) Instrumental Activities of Daily Living (IADL) Brief UCSD Performance-Based Skills Assessment (UPSA-B)
GOAL SETTING: SMS goal prompts - plan to increase
steps per week
SELF - MONITORING: Report pedometer
step counts via SMS
PERFORMANCE
FEEDBACK: MMS graphs
of step counts per week
GOAL REVIEW: SMS prompts to
review and adjust goals
INTENTION FORMATION: SMS prompts to select PA activities
iSTEP Approach
Control Theory: setting goals, monitoring behavior, receiving feedback, and reviewing goals after feedback represent the central basis of self-management.
1
2
3
4
5
iSTEP Focus Groups Conducted 2 focus groups with HIV+ individuals (n = 9,12) Group 1: Barriers and facilitators to PA Group 2: Intervention content and structure PA barriers: HIV- specific barriers (neuropathy, medication side effects) Depression Financial concerns Screen time PA Facilitators: Self-tracking/monitoring PA Incorporating PA into daily routine Support from peers and family Incentives
iSTEP Focus Groups Intervention components:
Strong support for goal-setting using pedometer step counts Variety of opinions expressed about message content: support for texts asking about amount of PA
limited interest in texts regarding HIV symptoms
some felt SMS texts to be most helpful, others liked the
idea of weekly picture graphs (MMS) for PA
a higher number of daily messages would lose impact
preference for texts at the same time vs. varied times each day
support for incentives, texts that emphasized achievements
iSTEP Intervention At baseline, iSTEP participants select personalized options: 1) top 5 barriers to PA (e.g., fatigue, finances, exercising alone) 2) personal locations where they can engage in PA (park, mall) 3) moderate PA activities (gardening, volunteer work, Frisbee) 4) a support friend to participate in PA (e.g., walking) 5) preferred times to receive their daily text messages Participants receive 3 text messages a day to encourage PA: 1) General PA tips and suggestions 2) Texts to promote walking 3) Reminders to engage in personal types of PA 4) Ideas to overcome personal PA barriers 5) PA benefits 6) Feedback evaluating message efficacy 7) Asked to report daily step counts every evening 8) Every Sunday: Interactive goal setting, e.g., increasing step counts by 10% per week
California Institute for Telecommunications and Information Technology (Calit2) SMS/MMS Platform
Milestone Messages
1860 Steps: 'Your total step count is more than walking up all the steps of the Empire State Building! 33,400 Steps: 'Congratulations! Your total step count is more miles than San Diego is to the US-Mexico border! 124,000 Steps: 'Your total step count is 124,000 steps, equivalent to the distance between the Earth and the beginning of outer space (62 miles)! 278,000 Steps: 'Your total step count is more than the distance from San Diego to Palm Springs!
Exercise Levels
Exercise Level Total Points Needed to Reach Each Level
Your Rank
Level 1 0 Beginner Walker Level 2 10,000 Basic Walker Level 3 25,000 Novice Walker Level 4 50,000 Apprentice Walker Level 5 75,000 Amateur Walker Level 6 100,000 Long Walker Level 7 150,000 Strong Walker Level 8 200,000 Expert Walker Level 9 250,000 Advanced Walker Level 10 300,000 Master Walker Level 11 400,000 Grandmaster Walker Level 12 500,000 Walker Level 13 650,000 Walker Level 14 800,000 Walker Level 15 1,000,000 Walker Level 16 1,250,000 Incredible Walker Level 17 1,500,000 Walker
1 point for each step, so 1000 steps = 1000 points 5,000 Bonus Points each week to respond to all the text messages 25,000 Bonus Points for completing each weekly step count goal
Example of daily SMS Messages: iSTEP (8:00 am): Good news! U have increased your weekly step count by 12%! Can U keep going and increase steps by 10% again this week? (Y/N) Participant response (8:02 am): N iSTEP (8:03 am): Can you tell me why? A Fatigue, D Pain in hands/feet, G medication effects, J Lack of time, P Other Participant response (8:03 am): A iSTEP (8:04 am): Feeling too tired for a long walk or long period of exercise? Aim for short walks - even 10 minutes is helpful to your health. iSTEP (2:30 pm): Research has shown that increasing your step count by 2000 steps or doing 20 min of daily brisk walking could reduce your risk of heart disease by 10%. iSTEP (10:00 pm): How many steps did you get in today? Txt back steps (####) Participant response (10:03 pm): 8750 iSTEP (10:04 pm): Excellent! Keep up the good work!
Future Directions
Focusing on HIV and aging – addressing the needs of older HIV+ persons Utilizing iSTEP to address other measures of interest in the HIV+ population – reducing risk for cardiovascular disease and metabolic disorders, examining effect of PA on inflammation Development of multi-level PA interventions that incorporate both individual and community/social group/worksite environments
Acknowledgements
HIV Neurobehavioral Research Program David Moore Jessica Montoya Megan Caines Manuel Romero John Gallardo Teresa Oyos Crossby Vargas Susan Concha-Garcia Matthew Dawson Donald Franklin Stephanie Corkran Michael Repinski
California Institute for Telecommunications and Information Technology Exercise and Physical Activity Resource Center David Wing Jeanne Nichols Kevin Patrick