855    

Background: Several studies show beneficial effects of r-hGH to reduce visceral adipose tissue (VAT) in HIV-1+ patients with lipodystrophy. Treatment effects on peripheral subcutaneous fat (fat depletion) remain to characterize. The present study explores effects on facial and thigh fat as well as on cholesterol of r-hGH 4 mg daily (A) or three times/week (B) over 12 weeks, followed by a 2 mg daily maintenance dose for an additional 12 weeks.

Methods: Patients with lipodystrophy were randomised to A or B. MRI scans were performed of the face and at mid thigh level at baseline, week 12 and week 24. Adverse events (AE) and clinical chemistry were documented every 4 weeks.

Results: 26 subjects (96% white, 96% male, mean age 44.8 y, mean duration of HIV 12.3 y) were included. Over 12 weeks treatment, abdominal adipose tissue was reduced by 60 cm² overall, while facial fat was reduced by 3.3 cm² and 2.6 cm² in A and B respectively (p=0.960, non significant dose comparison, NSDC). Over the 24 week study period, a total reduction of facial fat by 3.2 and 2.4 cm² was observed in A and B respectively (p=0.911,NSDC). Thigh fat, assessed in a small subset of patients, was reduced by 8.9 cm² and 5.3 cm² over 12 weeks (p=0.817, NSDC) and by 13.2 and 4.1 cm² over 24 weeks (p=0.316, NSDC) in A and B respectively, while leg circumference did not change. Total cholesterol was reduced by 31.3 and 8.1 mg/dl over 12 weeks in A and B respectively (p=0.046, significant dose comparison, SDC) and maintained over 24 weeks. There was a greater reduction in LDL in A than in B (28.9 vs 4.2 mg/dl at week 12 and 14.7 mg/dl vs 0.7 mg/dl at week 24) although not statistically significant different. There was a greater increase in HDL in A than in B (4.9 vs 2.4 mg/dl at week 12, NSDC and 7.1 mg/dl vs a reduction by 0.4 mg/dl at week 24, p=0.030, SDC). 4 patients in group A and 2 patients in group B discontinued due to AEs. No drug-related serious AE or newly onset diabetes occurred.

Conclusions: This study confirms previous reports that r-hGH effectively reduces VAT in lipodystrophic HIV+ patients, however optimal dose must be determined in large, randomized trials. Importantly, this exploratory study shows that facial and thigh peripheral fat reductions following 12 weeks treatment did not differ between 2 doses of r-hGH, and no further reduction was observed during maintenance therapy. Moreover, significant dose related improvements in total and HDL cholesterol levels were observed.

Keywords: growth hormone; lipodystrophy; cholesterol