growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting: a randomized, double-blind, placebo-controlled crossover trial. Am J Physiol Endocrinol Metab 289: E494 -E503, 2005. First published May 10, 2005 doi:10.1152/ajpendo.00013.2005.-Growth hormone (GH) treatment reverses the muscle loss allegedly responsible for diminished aerobic capacity and increased fatigue in patients with HIV-associated wasting. This study examined whether submaximal measures of physical performance can be used as objective measures of the functional impact of GH treatment-induced anabolism. We randomized 27 HIV-positive men [mean (SD) age, 43.9 (7.2) yr; body mass, 71.9 (10.4) kg; BMI, 23.1 (2.8) kg/m 2 ] with unintentional weight loss despite antiretroviral therapy to receive GH (6 mg) or placebo in a double-blinded, placebo-controlled, cross-over trial with a 3-mo washout. Lean body mass (LBM), maximum oxygen uptake (V O2 peak), ventilatory threshold (VeT), 6-min 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 mo of GH treatment vs. placebo (means Ϯ SE, 3.7 Ϯ 0.6 vs. 0.3 Ϯ 0.4 kg; P Ͻ 0.001). VeT significantly improved (17.6 Ϯ 3.7 vs. Ϫ5.9 Ϯ 2.5%; P Ͻ 0.001), but V O2 peak did not change significantly. 6MWT distance improved (24.9 Ϯ 9.7 vs. 19.9 Ϯ 11.6 m; P Ͼ 0.05) and 6MWT work increased significantly more after 3 mo of GH treatment (33.3 Ϯ 8.8 vs. 16.5 Ϯ 7.5 kJ; P Ͻ 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved, yet the changes were not statistically significant. GH treatment improved VeT linearly to the increase in LBM (r ϭ0.43, P ϭ 0.037) and 6MWT work (r ϭ 0.51, P ϭ 0.008), and the increase in 6MWT work correlated with increase in LBM (r ϭ 0.45, P ϭ 0.024). Improvement in 6MWT work above the median (27.3 kJ) showed a decrease in fatigue (r ϭ Ϫ0.62, P ϭ 0.024). We concluded that GH treatmentinduced LBM gains in HIV-associated wasting were functionally relevant, as determined by effort-independent submaximal measures of cardiopulmonary exercise testing.

The arteriovenous oxygen difference (a-vO(2) difference), a measure of peripheral muscle oxygen extraction-utilization during exercise, is reduced in antiretroviral-treated patients with human immunodeficiency virus (HIV), thus causing a shift in the cardiac output-oxygen consumption (Q-VO(2)) relationship. We investigated the impact of recombinant human GH (rhGH) treatment on a-vO(2) difference and the Q-VO(2) relationship during submaximal exercise by randomizing 12 HIV-infected patients (mean +/- sem: age, 43.3 +/- 1.5 yr; body mass, 69.5 +/- 2.9 kg; body mass index, 22.4 +/- 0.9 kg/m(2); maximum oxygen consumption, 33.6 +/- 1.5 ml/kg x min), with documented unintentional weight loss (>or=10% within the preceding 12 months) despite antiretroviral therapy, to receive 3 months of rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We assessed Q (determined noninvasively using CO(2) rebreathing), and subsequently a-vO(2) difference, from Q-VO(2) relationships. At study entry, the mean slope (8.1 +/- 1.0 liters/min x 1-liter increase in VO(2)) and intercept (3.1 +/- 1.3 liters/min), generated from each patient's Q-VO(2) relationship, were greater and lower, respectively, than those reported for healthy individuals (6.0 and 4.0, respectively), thereby indicating a deficit in the a-vO(2) difference. After 3 months of rhGH treatment, the slope decreased to 7.0, and the intercept increased to 3.5. After 1 month of rhGH treatment, the a-vO(2) difference (at a VO(2) of 1250 ml/min) significantly (P < 0.05) increased (17.1 +/- 8.9%) from baseline (9.92 +/- 0.51 ml/dl) and remained elevated (10.39 +/- 0.48 ml/dl) after 3 months of treatment. No significant changes were seen with placebo. Therefore, treatment with rhGH leads to an improvement in peripheral muscle oxygen extraction-utilization and the Q-VO(2) relationship during exercise in patients with HIV-associated wasting despite antiretroviral therapy.

SKF was more accurate than BIS when measuring body composition in patients with HIV wasting before and after rhGH treatment; nonetheless, the accuracy of BIS increased after treatment. Change in FM because of treatment was not accurately assessed with SKF.

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