Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat

• Published in: PloS one Vol. 10; no. 10; p. e0140358
• Main Authors: Mangili, Alexandra, Falutz, Julian, Mamputu, Jean-Claude, Stepanians, Miganush, Hayward, Brooke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.10.2015; Public Library of Science (PLoS)
• Subjects: Abdomen; Abdominal Fat - pathology; Acquired immune deficiency syndrome; Adipose tissue; Adolescent; Adult; Aged; AIDS; Alcohol; Alzheimer's disease; Antiretroviral drugs; Atherosclerosis; Body fat; Body mass; Body mass index; Body size; Cardiovascular disease; Care and treatment; Cholesterol; Clinical trials; Confidence intervals; Coronary vessels; Data processing; Diabetes; Diabetes mellitus; Drug dosages; Drug therapy; European Continental Ancestry Group; Female; Growth hormone; Growth hormone-releasing hormone; Growth Hormone-Releasing Hormone - adverse effects; Growth Hormone-Releasing Hormone - analogs & derivatives; Growth Hormone-Releasing Hormone - therapeutic use; Growth hormones; Health aspects; Health risk assessment; Health risks; HIV; HIV patients; HIV-Associated Lipodystrophy Syndrome - blood; HIV-Associated Lipodystrophy Syndrome - drug therapy; HIV-Associated Lipodystrophy Syndrome - ethnology; Human growth hormone; Human immunodeficiency virus; Humans; Insulin resistance; Insulin-like growth factors; Life assessment; Lipodystrophy; Male; Metabolic disorders; Metabolic syndrome; Metabolism; Middle Aged; Mortality; Obesity; Older people; Patients; Race; Randomization; Reduction; Risk factors; Somatotropin; Studies; Therapy; Triglycerides; Triglycerides - blood; Variance analysis; Viruses; Womens health; United States; Canada; Montreal Quebec Canada; United States > US; Massachusetts; Quebec Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140358

Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy. 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. 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. 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). 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.