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

• Published in: AIDS (London) Vol. 38; no. 12; pp. 1758 - 1764
• Main Authors: Russo, Samuel C, Ockene, Mollie W, Arpante, Allison K, Johnson, Julia E, Lee, Hang, Toribio, Mabel, Stanley, Takara L, Hadigan, Colleen M, Grinspoon, Steven K, Erlandson, Kristine M, Fourman, Lindsay T
• Format: Journal Article
• Language: English
• Published: England 01.10.2024
• Subjects: Absorptiometry, Photon; Adult; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Growth Hormone-Releasing Hormone - analogs & derivatives; Growth Hormone-Releasing Hormone - antagonists & inhibitors; Growth Hormone-Releasing Hormone - therapeutic use; HIV Infections - complications; HIV Infections - drug therapy; HIV Integrase Inhibitors - adverse effects; HIV Integrase Inhibitors - therapeutic use; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Placebos - administration & dosage; Treatment Outcome
• ISSN: 0269-9370; 1473-5571; 1473-5571
• DOI: 10.1097/QAD.0000000000003965

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. 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. 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. 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. 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.