Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.
This sub-analysis leveraged a randomized, double-blind, placebo-controlled trial of 61 people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease to assess whether tesamorelin remains effective and safe among those specifically on integrase inhibitor (INSTI)-based antiretroviral regimens. Of 38 participants on INSTIs at baseline, 15 (tesamorelin) and 16 (placebo) completed 12 months of follow-up. The study used MRI, proton MR spectroscopy, and DEXA to quantify visceral fat area, hepatic fat fraction, and trunk-to-appendicular fat ratio. The tesamorelin group showed statistically significant reductions in all three body composition endpoints compared to placebo. Metabolic safety outcomes, including rates of hyperglycemia, were similar between arms, and the drug was generally well tolerated. The authors note this is the first dataset specifically addressing tesamorelin use in PWH on INSTI-based regimens—an important gap given that phase III approval trials predated widespread INSTI use. Key limitations include the small sub-group sample size, the sub-analysis design (not powered for this specific comparison), and the predominantly research-selected population, which may limit generalizability.
Why this grade: Although drawn from a randomized double-blind trial in humans, this is a small sub-group analysis (n=31 completers) not independently powered for the INSTI-specific comparison, substantially limiting the strength of its conclusions.
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] cm 2 , 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.
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