目的:Tesamorelin是FDA批准的唯一治疗HIV感染者腹部脂肪堆积(PWH)的药物。在引入整合酶抑制剂(INSTIs)之前进行了III期临床试验,它们现在是艾滋病毒抗逆转录病毒疗法的支柱。
方法:我们利用一项针对61PWH和代谢功能障碍相关的脂肪变性肝病的随机双盲试验,在基线时评估替莫瑞林2mg每日一次与相同安慰剂的疗效和安全性。
方法:在母体临床试验中,内脏脂肪横截面积,肝脏脂肪分数,躯干与阑尾脂肪的比率使用磁共振成像进行量化,质子磁共振波谱,和双能X射线吸收法,分别,在基线和12个月。比较了治疗组之间的代谢和安全性结果。
结果:在38名参与者中,在基线时使用基于INSTI的方案,15名服用tesamorelin的个体和16名服用安慰剂的个体完成了为期12个月的研究。Tesamorelin导致内脏脂肪显着下降(中位数[四分位数范围]:-25[-93,-2]vs.14[3,41]cm2,P=0.001),肝脂肪(-4.2%[-12.3%,-2.7%]vs.-0.5%[-3.9%,2.7%],P=0.01),和躯干与阑尾脂肪比(-0.1[-0.3,0.0]vs.0.0[-0.1,0.1],P=0.03)。Tesamorelin的耐受性良好,两组之间的不良事件频率相似,包括高血糖。
结论:当前的分析提供了关于基于INSTI的方案的PWH中替莫瑞林的疗效和安全性的第一个专门数据。尽管使用INSTI与体重增加和脂肪组织功能障碍有关,替莫瑞林对身体成分有有益作用,且不会使血糖控制恶化.
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.
METHODS: 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.