physical activity and heart rate variability in hiv and methamphetamine dependence

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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


05

10152025303540 SD1

*

Non-linear Measures

0102030405060708090 SD2


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


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*


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


050

100150200250300350

Min

utes

Moderate Physical Activity

050

100150200250300350

Min

utes

Vigorous Physical Activity


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


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


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


% 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


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


Min

utes

Vigorous PA NC Normal (n = 14-24)


050

100150200250300350400450500


Min

utes

Moderate PA

NC Normal (n = 14-24)


0

200

400

600

800

1000

1200


Min

utes

Walking

NC Normal (n = 14-24)


*

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


Personalized PA text messages, setting PA goals, reporting step counts via SMS, weekly MMS graphs showing step count progress, participant feedback text questions



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

physical activity and heart rate variability in hiv and methamphetamine dependence

Health & Medicine

hiv hiv

effect of hiv

hiv drug userssmit

meth dependence henry

higher pa

reduced hrv

daily pa

improved hrv