title: Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.
abstract: BACKGROUND
  Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.
  
  
  OBJECTIVE
  1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.
  
  
  METHODS
  Data were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.
  
  
  RESULTS
  Metabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44).
  
  
  CONCLUSIONS
  Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mangili
authors.affiliation: HIV Metabolic Unit, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Falutz
authors.affiliation: Theratechnologies Inc., Montreal, Quebec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mamputu
authors.affiliation: PROMETRIKA, Cambridge, Massachusetts, United States of America.
authors.forename: Miganush
authors.initials: M
authors.lastname: Stepanians
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts, United States of America.
authors.forename: Brooke
authors.initials: B
authors.lastname: Hayward
mesh_terms: D050153:Abdominal Fat / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D044465:White People
chemical_list: D014280:Triglycerides; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin