Background:  This prospective, multi-center, randomized, dose-finding extension trial evaluated the efficacy and safety of r-hGH (Serostim) maintenance therapy, 1 or 2 mg daily, to sustain reductions of trunk fat and cholesterol concentrations induced by prior treatment with higher-dose r-hGH. In the antecedent STARS trial, r-hGH doses of 4 mg/day for 12 weeks significantly reduced trunk fat, visceral adipose tissue, total cholesterol, and non-HDL cholesterol, relative to placebo.

Methods:  Subjects included 142 HIV⁺ patients with excess trunk (including visceral) fat, without glucose intolerance, who initially had been randomized to r-hGH 4 mg/day or to alternate-day therapy or to placebo in the STARS trial for 24 weeks, and then were re-randomized to r-hGH 4 mg/day or alternate days for the first 12 weeks (period I) of this trial (weeks 24 to 36 from initiation of the STARS trial). Subsequently, 127 were re-randomized to receive 24 weeks of maintenance therapy (1 or 2 mg daily) during period II (weeks 12 to 36 of this trial, or 36 to 60 weeks from STARS trial baseline) and 119 completed 60 weeks. Among clinical endpoints assessed (at baseline, weeks 12, 24, 36, and 60) were trunk fat (DXA scan), total cholesterol, non-HDL cholesterol, and insulin area under the curve on oral glucose tolerance testing. Data were analyzed using 2-way ANOVA on ranked data with effects for treatment, sex, and their interaction.

Results:  Significant (p <0.05) reductions from the start of the STARS trial (baseline) to week 60 were found in both the 1 mg and 2 mg maintenance groups for trunk fat (-1.1, -1.4 kg from 9.5 and 9.8 kg), non-HDL cholesterol (-21.2, -23.8 from 175.6 and 172.1 mg/dL), and total cholesterol (-16.9, -18.5 from baselines of 213.0 and 209.2 mg/dL). Oral glucose tolerance testing revealed no change from baseline to week 60 in insulin area under the curve. There were no between-group differences in any parameters from baseline to weeks 36 or 60 among patients who received growth hormone 1-mg or 2-mg maintenance therapy, nor differences in incidence of most common adverse events, except for arthralgia (12.5% on 2 mg, 5.7% on 1 mg) during the 24 weeks that these therapies were administered.

Conclusions:  Based on its efficacy and safety profile, the 1-mg daily r-hGH dosage merits additional investigation as a maintenance therapy for HIV patients with excess trunk fat who have previously undergone r-hGH induction therapy at a higher r-hGH dose.

Keywords: growth hormone; cholesterol; lipodystrophy