Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Internal Medicine Department-Hospital Clínic of Barcelona (HCB), Barcelona, Spain.
PLoS One. 2019 May 23;14(5):e0216712. doi: 10.1371/journal.pone.0216712. eCollection 2019.
Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL).
Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point.
Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject.
In absence of HIV infection, or concomitant treatment, short-term exposure to T20 or RAL in healthy adult volunteers did not lead to any indicative changes in toxicity markers thus presuming the safe profile of both drugs.
经典的抗逆转录病毒药物可能会对 HIV 感染者和未感染者的代谢、线粒体、肾脏和肝脏功能产生急性影响。融合和整合酶抑制剂被认为更安全，但研究甚少。为了避免与 HIV 或其他抗逆转录病毒药物发生任何相互作用，我们在健康成年志愿者中评估了接受恩夫韦肽（T20）或拉替拉韦（RAL）治疗时这些毒性标志物的变化。
26 名健康参与者被随机分为 T20/90mg 与安慰剂（n = 12）或 RAL/400mg 与安慰剂（n = 14），每 12 小时给药一次，两个 7 天疗程之间有 4 周的洗脱期。主要终点是血脂谱（总胆固醇、高密度脂蛋白（HDL）-胆固醇、低密度脂蛋白（LDL）-胆固醇、甘油三酯）、胰岛素抵抗（葡萄糖）和线粒体毒性（外周血单核细胞中线粒体 DNA 含量-mtDNA）的变化。还分析了肾脏和肝脏毒性（肌酐、丙氨酸转氨酶（AST）、天冬氨酸转氨酶（ALT）、胆红素和总血浆蛋白）和整体安全性。评估了每个终点的周期、治疗和基础措施的影响。
T20 给药或 RAL 给药均未导致所评估的代谢、线粒体、肾脏或肝脏毒性标志物发生任何统计学上显著的变化。在任何受试者中均未发现任何表明药物毒性的症状。
在没有 HIV 感染或同时治疗的情况下，健康成年志愿者短期暴露于 T20 或 RAL 不会导致毒性标志物出现任何提示变化，从而假定这两种药物的安全性良好。
