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


  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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).

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

  9. 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.

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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.

  15. 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).

  16. Methodological Quality - Risk of Bias

  17. 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

  18. 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.

  19. 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

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

  21. kelly.obrien@utoronto.ca @kellyobrien25

  22. Extra slides

  23. 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

  24. 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.

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