HIV and Exercise: Updates from Two Cochrane Collaboration - PowerPoint PPT Presentation

HIV and Exercise: Updates from Two Cochrane Collaboration Systematic Reviews of Evidence Kelly O’Brien, Anne -Marie Tynan, Stephanie Nixon, Rick Glazier Department of Physical Therapy, University of Toronto OHTN Endgame I Conference Tuesday October 25, 2016

Presenter Disclosure • Presenter: Kelly O’Brien • Relationships with commercial interests • Grants / Research support: • Kelly O’Brien & Stephanie Nixon • Supported by CIHR New Investigator Awards • Rick Glazier • Department of Family and Community Medicine, St. Michael’s Hospital and University of Toronto

Background • People with HIV live longer and may experience physical, cognitive, social and psychological health-related challenges of HIV, multi-morbidity and aging. • Rehabilitation can assist in managing the health challenges (or disability) associated with HIV, and complex multi-morbidity. • However, few accessing formalized rehabilitation services (HIV Health and Rehabilitation Survey, 2016) • Exercise is one rehabilitation intervention and living strategy that can be used to mitigate health challenges and enhance health and promotion.

Purpose To assess the effectiveness of aerobic (AER) and/or progressive resistive exercise (PRE) on… • Immunological and virological • Cardiopulmonary • Weight and body composition • Strength and • Psychological outcomes among adults living with HIV

Methods – 2 systematic reviews Study Design • Systematic review using Cochrane Collaboration protocol. Inclusion Criteria • Randomized controlled trials comparing exercise with another intervention • Adults (18 years of age or older) living with HIV • Exercise at least 3 times per week for at least 4 weeks Study Selection • Electronic Databases (updates from 2009-2013) • Abstract review - 2 independent reviewers Data Extraction and Analysis • Data extraction • Cochrane Risk of Bias assessment – GRADE rating • Meta-analyses using random effects model & RevMan software

Results – Characteristics of Included Studies Characteristics Aerobic Exercise Resistive Exercise (PRE) Review Review # studies met inclusion criteria 24 studies 20 studies 14 studies overlap (PRE+AER; or PRE versus AER versus no exercise) # participants @ baseline 1242 participants 959 participants Mean age range (years) 30-49 years 32-49 years % women @ completion 22% 23% Withdrawal rate ~24% (0-76%) ~20% (0-38%) % studies published >1996 20 (83%) 17 (85%) Length of intervention 5 to 52 weeks 6 to 52 weeks Supervised exercise 18 (75%) 17 (85%) # meta-analyses performed 58 34

CD4 count (AER review) Aerobic (or AER+PRE) versus No Exercise No significant difference in change in CD4 count • Non-significant trend here towards increase in CD4 count among exercisers compared with non-exercisers (n=479; n=14 studies).

Viral load (AER review) Aerobic (or AER+PRE) versus No Exercise No significant difference in change in viral load between groups (n=162)

Cardiopulmonary Fitness: VO2max (AER) Aerobic (or AER+PRE) versus No Exercise Statistically significant (and potential clinically important) increase (improvement) in maximum oxygen capacity (VO2max) of 2.87 ml/kg/min (95% CI: 1.69, 4.04, n=358) for exercisers compared with non-exercisers.

Cardiopulmonary Fitness: Exercise Time Aerobic (or AER+PRE) versus No Exercise Statistically significant increase (improvement) in exercise time of 2.66 min (95% CI: 0.12, 5.19, n=129) for exercisers compared with non-exercisers.

Weight (PRE review) Aerobic (or AER+PRE) versus No Exercise Statistically significant increase in body weight of 2.50 kg (95% CI: 0.32, 4.67, n=129) for exercisers compared with non-exercisers. Assuming increase in body weight is favourable outcome; Potential for increase in muscle mass with PRE Greater increases with PRE versus no exercise (4.24 kg; 95% CI: 1.82, 6.66)

Body composition PRE versus no exercise (PRE review) Statistically significant increase in arm and thigh girth of 7.91 cm (95% CI: 2.18, 13.65, n=46) for exercisers compared with non-exercisers. PRE+AER versus no exercise (AER review) Statistically significant increase in leg muscle area of 4.79 cm 2 (95% CI: 2.04, 7.54, n=60) for exercisers compared with non-exercisers.

Body composition - % body fat (AER) Constant aerobic versus no exercise Statistically significant greater decrease in % body fat of 1.12% (95% CI:-2.18, -0.07, n=119) among exercisers compared with non- exercisers.

Strength: upper and lower body (PRE) PRE versus Aerobic exercise Statistically significant greater increase in upper body strength (combined 1RM or 3RM) of 14.56 kg (95% CI: 10.63, 18.49, n=41) and lower extremity strength 23.09 kg (95% CI: 13.01, 33.18) among PRE exercisers compared with AER exercisers.

Quality of life: SF36 questionnaire (AER) Aerobic (or AER+PRE) versus No Exercise Domain Weighted Mean Difference (WMD) (95% CI) General Health 4.73 (3.13, 9.75) Mental Health 11.58 (1.35, 21.81) Role Physical 6.56 (3.17, 9.96) Clinically Important Role Emotional 10.95 (8.19, 13.71) Improvement Pain -6.59 (-9.83, -3.36) Physical Function 16.30 (6.89, 25.72) Energy / Vitality 5.03 (1.33, 8.72) Social Function 2.73 (-4.84, 10.30) Statistically significant improvement on 6 out of 8 SF36 domain QOL sub- scales for exercisers compared with non-exercisers (n=59; 2 studies).

Methodological Quality - Risk of Bias

Conclusions Exercising at least 3X per week for at least 5 weeks is safe and can lead to improvements in…. • Cardiopulmonary Fitness • VO2max*, exercise time • Body Composition • Decrease in % body fat • Increases in weight*, arm and thigh girth*, leg muscle area among exercisers • Strength • Increase in upper and lower body strength among exercisers (greater increases among PRE versus AER)* • Quality of Life* What about CD4 count and Viral Load? • Despite trend towards improvement in CD4 count for some meta-analyses, majority continue to be non-significant

Considerations Methodological Quality • High risk of… • performance bias (inability to blind participants to exercise) • Withdrawal bias (results based on participants who completed the exercise) Majority of included studies… • Men, 30-49 years of age, little multi-morbidity • Resource rich countries • Highly supervised exercise by highly trained personnel • Trend towards combined AER and PRE interventions • Highly supervised settings by highly trained personnel • Sustainability in real world community setting over long term less clear.

For more detail - the full review https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1478-2 Effectiveness of Progressive Resistive Exercise (PRE) for Adults Living with HIV: Systematic Review and Meta-Analysis Using the Cochrane Collaboration Protocol – Under Review

Acknowledgements Stephanie Nixon & Kelly O’Brien Funded by CIHR New Investigator Awards Centre for Urban Health Studies, St. Michael’s Hospital

kelly.obrien@utoronto.ca @kellyobrien25

Extra slides

GRADE Rating – Quality of Evidence (AER) Outcomes WMD (95% confidence interval) # Quality of Interpretation participants evidence ⊕⊕⊕⊝ Viral Load 0.18 log10 copies higher in exercise 162 (6 RCTs) No significant difference MODERATE (log10 copies) group (95% CI: -0.13 to 0.48) in change in VL ⊕⊝⊝⊝ Cardiorespiratory 2.87 ml/kg/min higher in exercise group 358 (8 RCTs) Significant improvement (VO2max; ml/kg/min) (95% CI: 1.69 to 4.04) VERY LOW in VO2max ⊕⊕⊝⊝ Strength 11.86 1RM higher in exercise group 44 (2 RCTs) Significant improvement LOW (upper body chest (95% CI: 2.37 to 21.36) in upper body strength press; 1RM) ⊕⊝⊝⊝ Strength (lower body leg 50.96 1RM higher in exercise group 44 (2 RCTs) No significant difference; press; 1RM) (95% CI: - 13.01 to 114.92) VERY LOW trend towards increase ⊕⊕⊕⊝ Weight (kg) 0.38 kg higher in exercise group (95% 151 (5 RCTs) No significant difference MODERATE CI: -1.55 to 2.31) in change ⊕⊕⊕⊕ Body Composition (body 0.07 kg/m2 higher in the exercise group 227 (6 RCTs) No significant difference mass index; kg/m2) (95% CI: -0.52 to 0.66) HIGH in change ⊕⊝⊝⊝ Quality of Life (SF36 6.47 points higher in exercise group 472 (2 RCTs) Significant improvement VERY LOW subscale scores) (95% CI: 3.18 to 9.75) in QOL scores

Body Composition: Lean Body Mass Aerobic (or AER+PRE) versus No Exercise Statistically significant increase in lean body mass of 1.75 kg (95% CI: 0.13, 3.37, n=89) for exercisers compared with non-exercisers.