TAILoR (TelmisArtan and InsuLin Resistance in Human Immunodeficiency Virus [HIV]): An Adaptive-design, Dose-ranging Phase IIb Randomized Trial of Telmisartan for the Reduction of Insulin Resistance in HIV-positive Individuals on Combination Antiretroviral Therapy.
TAILoR (TelmisArtan and InsuLin Resistance in Human Immunodeficiency Virus [HIV]): An Adaptive-design, Dose-ranging Phase IIb Randomized Trial of Telmisartan for the Reduction of Insulin Resistance in HIV-positive Individuals on Combination Antiretroviral Therapy.
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TAILoR（人类免疫缺陷病毒 [HIV] 中的替米沙坦和胰岛素抵抗）：替米沙坦的一项适应性设计、剂量范围 IIb 期随机试验，用于减少接受抗逆转录病毒联合治疗的 HIV 阳性个体的胰岛素抵抗。
DOI：
10.1093/cid/ciz589
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Pushpakom S
中科院分区：
文献类型：
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作者：
Pushpakom S
背景联合抗逆转录病毒治疗可导致代谢异常，增加心血管疾病的风险。我们评估了替米沙坦是否能降低人类免疫缺陷病毒（HIV）阳性个体的胰岛素抵抗对antiretrovirals.MethodsWe进行了多中心，随机，开放标签，剂量范围控制试验替米沙坦。接受联合抗逆转录病毒治疗的HIV感染受试者被随机分为两组，一组为无干预（对照组），另一组为20、40或80 mg替米沙坦，每日一次。适应性设计允许在第I阶段检测所有剂量的替米沙坦，并将有希望的剂量纳入第II阶段。主要结果的措施是减少稳态模型评估的胰岛素抵抗（HOMA-IR）在24 weeks.ResultsA共招募了377例患者。在I期，48、49、47和45例患者分别随机接受对照组和20、40和80 mg替米沙坦组（总n = 189）。在中期分析时，将80 mg替米沙坦转入II期。在II期结束时（n = 105，对照组; 106，80 mg组），替米沙坦（80 mg）和非干预组之间在24周时的HOMA-IR（估计效应，0.007; SE，0.106）无差异。48周的纵向分析显示HOMA-IR、脂质或脂肪因子水平无变化。有显著（P≤ .05），但修订后的定量胰岛素敏感性检查指数（QUICKI）略有改善（0.004）和血浆hs-CRP（-0.222毫克/升）和肝脏脂肪含量减少（平均减少1.714; P= .005）。结论替米沙坦对主要结局（HOMA-IR）无显著影响，但在一些次要结局指标方面略有改善。需要对这一人群进行进一步研究，以确定预防心血管疾病发病率和死亡率的新策略。临床试验注册ISRCTN注册（51069819）。
BackgroundCombination antiretroviral therapy results in metabolic abnormalities which increase cardiovascular disease risk. We evaluated whether telmisartan reduces insulin resistance in human immunodeficiency virus (HIV)–positive individuals on antiretrovirals.MethodsWe conducted a multicenter, randomized, open-label, dose-ranging controlled trial of telmisartan. Participants with HIV infection receiving combination antiretroviral therapy were randomized equally to either no intervention (control) or 20, 40, or 80 mg telmisartan once daily. The adaptive design allowed testing of all dose(s) of telmisartan in stage I, with the promising dose(s) being taken into stage II. The primary outcome measure was reduction in homeostasis model assessment of insulin resistance (HOMA-IR) at 24 weeks.ResultsA total of 377 patients were recruited. In stage I, 48, 49, 47, and 45 patients were randomized to control and 20, 40, and 80 mg telmisartan, respectively (total n = 189). At the interim analysis, 80 mg telmisartan was taken forward into stage II. At the end of stage II (n = 105, control; 106, 80-mg arm), there were no differences in HOMA-IR (estimated effect, 0.007; SE, 0.106) at 24 weeks between the telmisartan (80 mg) and nonintervention arms. Longitudinal analysis over 48 weeks showed no change in HOMA-IR, lipid or adipokine levels. There were significant (P≤ .05), but marginal, improvements in revised Quantitative Insulin Sensitivity Check Index (QUICKI) (0.004) and plasma hs-CRP (−0.222 mg/L) and reduction in liver fat content (1.714 mean reduction;P= .005).ConclusionsNo significant effect of telmisartan was demonstrated on the primary outcome (HOMA-IR), but there were marginal improvements with some secondary outcome measures. Further studies in this population are warranted to identify novel strategies for preventing cardiovascular morbidity and mortality.Clinical Trial RegistrationISRCTN registry (51069819).