Phase III sub-analysis of 410 HIV-positive patients randomized to tesamorelin or placebo for 26 weeks, examining changes in circulating inflammatory and fibrinolytic markers (PAI-1, tPA, CRP, adiponectin) and correlating changes with VAT reduction, demonstrating that tesamorelin-mediated VAT reduction improved PAI-1 and other inflammatory markers. Establishes tesamorelin's cardiovascular risk-relevant anti-inflammatory effects. Provides clinical evidence that tesamorelin reduces pro-thrombotic and inflammatory biomarkers through VAT reduction—establishing that HIV-associated visceral adiposity drives cardiovascular risk through modifiable inflammatory pathways and that tesamorelin treatment reduces these risk factors beyond lipid improvements.
Abstract
OBJECTIVE: To report the effects of tesamorelin, a growth hormone-releasing hormone analogue, on inflammatory and fibrinolytic markers and to relate these effects to changes in visceral adipose tissue (VAT).
DESIGN AND METHODS: Four hundred and ten HIV-infected patients with abdominal adiposity were randomized to 2 mg tesamorelin (n = 273) or placebo (n = 137) subcutaneously daily for 26 weeks. Circulating plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, C-reactive protein (CRP), and adiponectin were assessed.
RESULTS: At baseline, VAT was significantly associated with PAI-1 antigen (ρ = 0.36, P < 0.001), tPA antigen (ρ = 0.29, P < 0.001), CRP (ρ = 0.18, P < 0.001), and adiponectin (ρ = -0.22, P < 0.001). Treatment with tesamorelin resulted in a significant decrease from baseline in tPA antigen (-2.2 ± 2.5 vs. -1.6 ± 2.9 ng/ml, tesamorelin vs. placebo, P < 0.05). Changes in PAI-1 antigen were not significant in the tesamorelin group compared to placebo. Among patients receiving tesamorelin, changes in inflammatory markers were associated with change in VAT (PAI-1 antigen: ρ = 0.16, P = 0.02; tPA antigen: ρ = 0.16, P = 0.02; adiponectin: ρ = -0.27, P < 0.001), and these associations remained significant when controlling for changes in insulin-like growth factor-1.
CONCLUSION: In HIV patients with abdominal adiposity, tesamorelin may have a modest beneficial effect on adiponectin and fibrinolytic markers in association with changes in VAT. Further studies are needed to determine the clinical significance of these changes. These data further highlight the deleterious role of excessive VAT and the utility of strategies to improve VAT in this population.
Authors
Stanley, Takara L; Falutz, Julian; Mamputu, Jean-Claude; Soulban, Graziella; Potvin, Diane; Grinspoon, Steven K