Blunted Increase in Muscle Mass

After Exercise Training in People Aging with HIV

Catherine M. Jankowski, PhD1, Melissa P. Wilson, MS2, Todd T. Brown, MD3, Samantha MaWhinney, ScD2, Kristine M.

Erlandson, MD4

(1) College of Nursing, University of Colorado, Aurora, CO, USA(2) Department of Biostatistics, School of Public Health, University of Colorado(3) Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine,

Johns Hopkins University, Baltimore, MD, USA(4) Division of Infectious Diseases, Department of Medicine, University of Colorado

Gilead Sciences, Merck, ViiV, Theratecnologies (KME, TTB)

No conflicts: CMJ, MPW, SM

Conflict Disclosures

Funding provided by:

Gilead Sciences Research Scholars Program in HIV (KME); K23 AG050260 (KME); K24 A1120835 (TTB); Colorado CTSA UL 1TR002535 (KME, CMJ).

Aging with HIV

• Newer anti-retroviral therapies (ART) have

o prolonged life of people living with HIV (PWH)

o mitigated muscle wasting & lipodystrophy

• With aging, PWH face sarcopenia & increasing adiposity

• Physical function improved in older PWH & uninfected

controls after exercise training

VO2 peak, 400-m walk time, muscle strength

Erlandson et al, AIDS; 2018

Questions & Objective

1. What were the changes in body composition with

exercise?

2. Any unique adaptations in older PWH?

Objective: To compare changes in lean mass,fat mass, & visceral fat area in PWH and controls

Exercise for Healthy Aging Study (NCT 02404792)

• Aged 50-75 years

• Sedentary (exercise < 60 min/week)

• BMI 20-40 kg/m2

• No contraindications for exercise

• Sex hormone therapy stable, physiologic levels, no IM testosterone (T)

• Stable ART > 2 years

• Undetectable HIV-1 RNA > 2 years

• CD4 T-cell count > 200 cells/µL

All Participants PWH

Cardiovascular & Resistance Exercise 3 days/week

Screening

✓ GXTVO2 peak

✓ 1-RMstrength

Weeks 1-12 Weeks 13-24Randomized

DXA DXA

Intervention

Baseline comparisons• Two-sample t-tests

Exercise effects

• Multivariable regression

• HIV serostatus as primary predictor

• Adjusted for

baseline values

age (or VACS)

exercise adherence

P < 0.05

Dual-energy X-ray Absorptiometry

Hologic Delphi-W Total body scans @ weeks 0, 24

• Total lean mass

• Appendicular lean mass (ALM/m2)

∑ limb lean mass/height2

• Total fat mass

• Visceral adipose tissue area (VAT)

Body Composition by DXA Statistical Analyses

Methods

Participant Characteristics (% or median [IQR])

PWH (n=27)

Controls (n=28)

Male, % 93 93

Race, % white 70 89

Non-Hispanic, % 85 86

Age, years 56 [52, 61] 60 [54, 64]

VACS-1 > 20 points, % 59* 25*

Statin use, % 48 43

Testosterone use, % 20 8

Years since HIV diagnosis 23 [16, 28] ---

CD4 count, cells/uL 546 [416, 772] ---

ART duration, years 17 [8, 19] ---

Exercise Characteristics

Sessions attended, % 89 [82, 86] 87 [81, 92]

Randomized to HighIntensity, %

56 50

PWH were more likely to have higher

comorbidity burden(P=0.02).

Current ART:59% INSTI4% TAF

Current / prior thymidine analogues: 68%

BMI & Fat Mass were significantly lower in PWH

Baseline Body Composition (Mean (95%CI) or %)

PWH (n=27)

Controls (n=28)

P-value

BMI, kg/m2 26.925.0, 28.0

29.6280, 31.0

0.019

Total Lean Mass, kg 57.754.2, 61.1

60.056.4, 63.6

0.337

Appendicular Leanmass/m2

8.68.1, 9.1

8.98.5, 9.3

0.262

Total Fat Mass, kg 20.617.7, 23.6

27.224.0, 30.4

0.003

Visceral Adipose Tissue Area, cm2

184151, 217

211184, 237

0.204

Sarcopeniaa, % 15 4

Lipodystrophyb, % 26 --

a Baumgartner et al, 1998; b Bonnet et al, 2005

Changes in Response to Exercise Were Not HIV-specific

Mean (95% CI)Within Group: * P < 0.05 ** P < 0.01Adjusted for baseline values, age, and exercise adherence

• HIV infection was not a significant determinant of changes in body composition w/exercise.

Held true after adjusting for comorbidity

• HIV may blunt the increases in lean mass

More emphasis on resistance exercise to increase lean mass in PAWH?

# exercises, volume, frequency

• Total & visceral fat were reduced Improved cardiometabolic risk

• Maintenance of lean mass while losing fat is a positive outcome of exercise in older adults

Conclusions

Limitations• Predominantly male• Change in exercise intensity at 12 weeks• HIV status x exercise intensity underpowered

Strengths• Supervised exercise• Head-to-head comparisons of PWH & controls• Exercise protocol based on (former) public

health recommendations (2008)

• Define effective exercise interventions for aging PWH

Improve body composition, fitness & function Current exercise recommendations are meager

(ACSM, 2018)

• Expand sample size & diversity

• Promote retention of exercise beyond supervised protocols

Actionable behavioral strategies

• Investigate mitochondrial adaptations in muscle of PWH during aging and exercise

Future Directions

Thank YOU!

Overarching Goal: To

Promote Excellence in

Aging with HIV

Questions??