Submitted on January 12, 2005
Accepted on May 5, 2005
Anabolic Growth Hormone Action Improves Submaximal Measures of Physical Performance in Patients with HIV-Associated Wasting
John G Esposito1, Scott G Thomas2, Lori Kingdon3, and Shereen Ezzat4*
1 Graduate Department of Rehabilitation Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2 Graduate Department of Rehabilitation Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Graduate Dept. of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada
3 Freeman Centre for Endocrine Oncology, University of Toronto, Toronto, Ontario, Canada
4 Freeman Centre for Endocrine Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Faculty of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: sezzat{at}mtsinai.on.ca.
Recombinant human growth hormone (rhGH) treatment reverses the muscle loss allegedly responsible for the diminution of aerobic capacity and increased fatigue in patients with human immunodeficiency virus (HIV)-associated wasting. The aim of this study was to determine whether submaximal measures of physical performance can be used as objective measures of the functional impact of rhGH treatment-induced anabolism in patients with HIV-associated wasting. We randomized 27 HIV-positive men (mean [SD] age: 43.9 [7.2] years; body mass: 71.9 [10.4] kg; body mass index: 23.1 [2.8] kg per m-2), with documented unintentional weight loss (
10% over preceding 12 months) despite antiretroviral therapy, to receive daily injections of rhGH (6mg) or placebo, self-administered for 3 months, in a double-blinded placebo-controlled cross-over trial with a three-month washout. Lean body mass (LBM), maximum oxygen uptake (VO2peak), ventilatory threshold (VeT), six-minute walk test (6MWT) distance and work, Profile of Mood States (POMS) fatigue and vigor scores, and Nottingham Health Profile (NHP) energy and physical mobility scores were measured. LBM significantly increased after 3 months of rhGH treatment vs placebo (mean [SEM] 3.7 [0.6] kg vs 0.3 [0.4] kg, P < 0.001). VeT significantly improved (17.6 [3.7] % vs -5.9 [2.5] %, P < 0.001) but VO2peak did not change significantly. 6MWT distance improved (24.9 [9.7] m vs 19.9 [11.6] m, P > 0.05) and 6MWT work increased significantly more after 3 months of rhGH treatment relative to placebo (33.3 [8.8] kJ vs 16.5 [7.5] kJ, P < 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved after active treatment, yet the changes were not statistically significant versus those after placebo. Following 3 months of rhGH treatment, the improvement in VeT was linearly related to the increase in LBM (r = 0.43, P = 0.037) and 6MWT work (r = 0.51, P = 0.008) and the increase in 6MWT work correlated with the increase in LBM (r = 0.45, P = 0.024). Patients who demonstrated an improvement in 6MWT work above the median (27.3 kJ) also showed a decrease in reported fatigue (r = -0.62, P = 0.024). We conclude that rhGH treatment-induced LBM gains in patients with HIV-associated wasting are functionally relevant as determined by associated improvements in objective effort-independent submaximal measures of cardiopulmonary exercise testing.
