HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation, loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from the first Phase 3 multicenter, randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV- infected patients with excess of abdominal fat accumulation for 26 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with lesser changes in limb fat and subcutaneous adipose tissue (SAT). The present study is aimed at confirming the observations made during the first Phase 3 study.

• Lipodystrophy
• HIV Infections

Inclusion Criteria:

• Age 18 to 65 years inclusive;
• HIV positive; CD4 cell counts >100 cells/mm3; viral load <10 000 copies/mL stable for 8 weeks;
• On stable ART regimen for at least 8 weeks prior to randomization;

• Have evidence of abdominal fat accumulation defined by the following anthropometric cut off values:

  • For males: waist circumference > 95 cm and waist to hip ratio > 0.94;
  • For females: waist circumference > 94 cm and waist to hip ratio > 0.88;
• Females of childbearing potential, not pregnant or lactating,
• For female subjects, normal mammography within 6 months of study;
• Signed informed consent.

Exclusion Criteria:

• Body Mass Index < 20 kg/m2;
• Opportunistic infection; HIV-related disease within 3 months of study;
• History of malignancy; active neoplasm;
• Prostate-specific antigen (PSA) >5 ng/mL at screening;
• Hypopituitarism; history of pituitary tumor/surgery; head irradiation; head trauma that has affected the somatotropic axis;
• Untreated hypothyroidism;
• Use of oral hypoglycemic or insulin sensitizing agent within 6 months of study (includes type 1 and drug-treated type 2 diabetes);
• ALT or AST >3 x ULN; serum creatinine >133 umol/L (1.5 mg/dL); hemoglobin more than 20 g/L below LLN; fasting blood glucose ≥ 8.33 mmol/L (150 mg/dL); fasting triglycerides > 11.3 mmol/L (0.99 g/dL);
• Untreated hypertension;
• Change in anti-hyperlipemic regimen within 3 months prior to study;
• Change in testosterone regimen and/or supraphysiological dose of testosterone;
• Estrogen therapy;
• Anoretics/anorexigenics or anti-obesity agents within 3 months of study;
• Growth hormone (GH), GH secretagogues, growth hormone-releasing factor (GRF) products, IGF-1, or IGFBP-3 within 6 months of study;
• Drug or alcohol dependence or use of methadone within 6 months of study entry;
• Participation in a clinical trial with any investigational drug/device within 30 days of screening.