Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial.

CONTEXT: Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor.

OBJECTIVE: To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency.

DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007.

INTERVENTION: Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 microg/kg/d and increased to maximum dose of 6 microg/kg/d (average dose, 0.33 mg/d).

MAIN OUTCOME MEASURES: Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data.

RESULTS: Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n = 56}, -19 cm(2); 95% confidence interval {CI}, -37 to -0.3 cm(2)], -19 cm(2); 95% CI, -38 to -0.5 cm(2); P = .049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P = .04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P = .006); and triglycerides (-7 mg/dL, P = .002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P = .009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P < .001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P = .70).

CONCLUSIONS: In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00100698.