Brasilmed Assistência Médica e Pesquisas, Federal University of Sao Paulo, Brazil.
J Infect Dis. 2010 Feb 15;201(4):590-9. doi: 10.1086/650342.
Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy.
This double-blind, dose-ranging, phase 2 trial randomized subjects to receive 30 mg or 20 mg of vicriviroc or placebo once daily plus re-optimized background therapy containing a protease inhibitor with ritonavir. Subjects were adults infected with CCR5-tropic HIV who were experiencing failure of triple antiretroviral regimens. The primary end point was mean change in baseline log(10) HIV RNA level at 48 weeks, based on an intent-to-treat analysis.
One hundred fourteen persons received vicriviroc at 30 mg (n = 39), vicriviroc at 20 mg (n =40), or placebo (n = 35). The mean change in baseline HIV RNA level at week 48 was -1.77 log(10) copies/mL for 30 mg of vicriviroc and -1.75 log(10) copies/mL for 20 mg of vicriviroc, compared with -0.79 log(10) copies/mL for placebo (P =.002 and P=.003, respectively, compared with placebo). Mean CD4 counts increased by 102, 136, and 63 cells/mm(3) for 30 mg vicriviroc, 20 mg vicriviroc, and placebo, respectively (P = .260 and P = .039, respectively, compared with placebo). Rates of adverse events (mostly mild-to-moderate) were 111.4, 112.5, and 147.4 events per 100 subject-years, respectively.
Vicriviroc administered with a protease inhibitor plus ritonavir-containing regimen shows potent antiretroviral and immunologic activity sustained over 48 weeks in treatment-experienced patients.
NCT00243230 .
阻断人免疫缺陷病毒（HIV）的 CCR5 辅助受体的药物已显示出强大的抗逆转录病毒活性。在早期的临床研究中，CCR5 拮抗剂维立西罗证明是一种安全有效的联合抗逆转录病毒治疗药物。
这是一项双盲、剂量范围、2 期临床试验，将受试者随机分为每天接受 30 毫克或 20 毫克维立西罗或安慰剂，同时接受优化背景治疗，包括含利托那韦的蛋白酶抑制剂。受试者为感染 CCR5 嗜性 HIV 的成年人，他们正在经历三联抗逆转录病毒方案失败。主要终点是根据意向治疗分析，48 周时基线 log10 HIV RNA 水平的平均变化。
114 名患者接受了 30 毫克维立西罗（n=39）、20 毫克维立西罗（n=40）或安慰剂（n=35）。第 48 周时，30 毫克维立西罗组的基线 HIV RNA 水平平均下降 1.77 log10 拷贝/ml，20 毫克维立西罗组下降 1.75 log10 拷贝/ml，安慰剂组下降 0.79 log10 拷贝/ml（分别与安慰剂相比，P=.002 和 P=.003）。30 毫克维立西罗、20 毫克维立西罗和安慰剂组的平均 CD4 计数分别增加 102、136 和 63 个细胞/mm3（分别为 P=.260 和 P=.039，与安慰剂相比）。不良事件发生率（主要为轻至中度）分别为 111.4、112.5 和 147.4 例/100 人-年。
维立西罗与蛋白酶抑制剂加利托那韦联合治疗方案联合治疗，在治疗经验丰富的患者中，持续 48 周显示出强大的抗逆转录病毒和免疫活性。
NCT00243230。
