Girard Pierre-Marie, Cabié André, Michelet Christian, Verdon Renaud, Katlama Christine, Mercié Patrick, Morand-Joubert Laurence, Pétour Pascal, Monchecourt Françoise, Chêne Geneviève, Trylesinski Aldo
Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Paris VI, Paris, France.
J Antimicrob Chemother. 2009 Jul;64(1):126-34. doi: 10.1093/jac/dkp141. Epub 2009 Apr 29.
To assess simplified maintenance regimens containing dual antiretroviral drugs in patients with controlled human immunodeficiency virus type 1 infection.
A non-inferiority, randomized, multicentre, open-label trial was performed in 24 AIDS clinical centres in France randomizing 143 patients [treated for >or=6 months, plasma viral load (pVL) <50 copies/mL, no prior history of treatment failure] to receive a two-drug regimen [tenofovir disoproxil fumarate (tenofovir DF) and efavirenz] or to maintain a three-drug treatment (tenofovir DF, lamivudine and efavirenz). The main outcome measure was the success rate (percentage of patients with pVL <50 copies/mL without treatment modifications) at week 48.
Success rates for the intention-to-treat analysis were 97.2% (70/72) versus 81.7% (58/71) in the three-drug versus two-drug maintenance regimen groups, respectively [difference, 15.5%; upper limit of one-sided 95% confidence interval (CI), 23.7%], and 100% (70/70) versus 90% (54/60) for the per protocol analysis, respectively (difference, 10%; upper limit of one-sided 95% CI, 16.4%), with a non-inferiority margin set at 14%. Three patients from the two-drug group experienced virological failure with selection of efavirenz-associated mutations. Overall, CD4 counts were significantly increased from baseline (median, +24 cells/mm(3); P = 0.007). Four patients discontinued study treatment due to adverse events in the two-drug group and none in the three-drug group. No significant changes in creatinine clearance or phosphataemia were reported. Overall, levels of triglycerides, total and high-density lipoprotein cholesterol were improved; low-density lipoprotein cholesterol was improved only in the three-drug group.
The non-inferiority of the two-drug versus the three-drug regimen was not demonstrated. Lipid parameters improved after switching from twice-daily highly active antiretroviral therapy (HAART) to once-daily tenofovir-based HAART.
评估含两种抗逆转录病毒药物的简化维持治疗方案用于1型人类免疫缺陷病毒感染得到控制的患者的情况。
在法国24个艾滋病临床中心进行了一项非劣效性、随机、多中心、开放标签试验，将143例患者（治疗≥6个月，血浆病毒载量[pVL]<50拷贝/mL，无既往治疗失败史）随机分组，分别接受双药方案（替诺福韦酯富马酸盐[替诺福韦DF]和依非韦伦）或维持三联治疗（替诺福韦DF、拉米夫定和依非韦伦）。主要结局指标是第48周时的成功率（pVL<50拷贝/mL且未调整治疗的患者百分比）。
意向性分析的成功率在三联维持治疗方案组和双药维持治疗方案组中分别为97.2%（70/72）和81.7%（58/71）[差异为15.5%；单侧95%置信区间（CI）上限为23.7%]，符合方案分析分别为100%（70/70）和90%（54/60）（差异为10%；单侧95%CI上限为16.4%），非劣效性界值设定为14%。双药组有3例患者出现病毒学失败，并出现了与依非韦伦相关的突变。总体而言，CD4细胞计数较基线显著增加（中位数，+24个细胞/mm³；P = 0.007）。双药组有4例患者因不良事件停止研究治疗，三联组无患者因不良事件停药。未报告肌酐清除率或血磷有显著变化。总体而言，甘油三酯、总胆固醇和高密度脂蛋白胆固醇水平有所改善；低密度脂蛋白胆固醇仅在三联组有所改善。
未证明双药方案相对于三联方案的非劣效性。从每日两次高效抗逆转录病毒治疗（HAART）转换为每日一次的基于替诺福韦的HAART后，血脂参数有所改善。
