Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors

Abstract

Objective: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. Design: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline. Methods: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. Results: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: −25 [−93, −2] vs. 14 [3, 41] cm2, P = 0.001), hepatic fat (−4.2% [−12.3%, −2.7%] vs. −0.5% [−3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (−0.1 [−0.3, 0.0] vs. 0.0 [−0.1, 0.1], P = 0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups. Conclusions: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.