Effects of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor Analog, in Human Immunodeficiency Virus-Infected Patients with Excess Abdominal Fat: A Pooled Analysis of Two Multicenter, Double-Blind Placebo-Controlled Phase 3 Trials with Safety Extension Data

Context: HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT). Objective: Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat. Design and Setting: Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension. Patients: A total of 806 ART-treated HIV patients with excess abdominal fat were randomized in a 2:1 fashion to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) sc daily. At wk 26, patients initially on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 246) or placebo (T-P, n = 135) for an additional 26 wk, whereas patients on placebo were switched to tesamorelin (P-T, n = 197). Interventions: Tesamorelin (GHRH1–44) at a dose of 2 mg or identical placebo, sc, was given daily. Main Outcome Measure: We evaluated percent change in VAT by computed tomography scan at wk 26. Results: At wk 26, VAT decreased significantly in tesamorelin-treated patients (−24 ± 41 vs. 2 ± 35 cm2, tesamorelin vs. placebo, P < 0.001; treatment effect, −15.4%). No significant changes were observed in abdominal sc adipose tissue (−2 ± 32 vs. 2 ± 29 cm2, P = 0.08; treatment effect, −0.6%). Treatment with tesamorelin resulted in significant decreases in triglycerides (−37 ± 139 vs. 6 ± 112 mg/dl, P < 0.001; treatment effect, −12.3%) and cholesterol to high-density lipoprotein ratio (−0.18 ± 1.00 vs. 0.18 ± 0.94, P < 0.001; treatment effect, −7.2%) vs. placebo. Tesamorelin improved body image [belly appearance distress (P = 0.002)], patient rating of belly profile (P = 0.003), and physician rating of belly profile (P < 0.001). Mean IGF-I increased 108 ± 112 vs.−7 ± 64 ng/ml (P < 0.001 vs. placebo). At wk 52, decreases in VAT [−35 ± 50 cm2 (−17.5 ± 23.3%)], waist circumference (−3.4 ± 6.0 cm), triglycerides (−48 ± 182 mg/dl), cholesterol (−8 ± 38 mg/dl), and non-high-density lipoprotein (−7 ± 38 mg/dl) were maintained (all P < 0.001 vs. original baseline) in the T-T group. Treatment with tesamorelin was generally well tolerated. No clinically meaningful differences were observed between groups in glucose parameters at wk 26 and 52. Conclusions: Treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal sc adipose tissue, improves body image and lipids, and is overall well toler