Maraviroc for previously treated patients with R5 HIV-1 infection.
Maraviroc for previously treated patients with R5 HIV-1 infection.
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DOI：
10.1056/nejmoa0803152
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发表时间：
2008-10-02
期刊：
影响因子：
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通讯作者：
MOTIVATE Study Teams
中科院分区：
文献类型：
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作者：
Gulick RM;Lalezari J;Goodrich J;Clumeck N;DeJesus E;Horban A;Nadler J;Clotet B;Karlsson A;Wohlfeiler M;Montana JB;McHale M;Sullivan J;Ridgway C;Felstead S;Dunne MW;van der Ryst E;Mayer H;MOTIVATE Study Teams
CC趋化因子受体5拮抗剂是一类新的抗逆转录病毒药物。我们进行了两项双盲、安慰剂对照、III期研究-马拉韦罗与优化疗法在病毒血症抗逆转录病毒治疗经验患者中的比较（MOTIVATE）1和MOTIVATE 2 -仅感染R5人类免疫缺陷病毒1型（HIV-1）的患者。他们曾接受过三种抗逆转录病毒药物治疗或对三种抗逆转录病毒药物产生耐药性，HIV-1 RNA水平超过每毫升5000拷贝。这些患者被随机分配到三种抗逆转录病毒方案之一，包括每日一次马拉韦罗，每日两次马拉韦罗或安慰剂，每种方案都包括基于治疗史和耐药性测试的优化背景治疗（OBT）。48周后评估安全性和有效性。共有1049名患者接受了随机分配的研究药物;平均基线HIV-1 RNA水平为72，400拷贝/毫升，中位CD 4细胞计数为169/立方毫米。在48周时，在两项研究中，马拉韦罗组HIV-1 RNA较基线的平均变化大于安慰剂组：在MOTIVATE 1中，每日一次和每日两次方案分别为-1.66和-1.82 log 10拷贝/毫升，安慰剂为-0.80，分别为-1.72和-1.87 log 10拷贝/毫升，而动机2中安慰剂组为-0.76。更多接受马拉韦罗每日一次或两次治疗的患者HIV-1 RNA水平低于50拷贝/毫升（MOTIVATE 1中分别为42%和47%，安慰剂组为16%;两个马拉韦罗组为45%，MOTIVATE 2为18%;每项研究中两个比较的P<0.001）。与安慰剂相比，马拉韦罗每日1次或2次治疗组的CD 4计数较基线的变化也更大（MOTIVATE 1组分别增加113和122每立方毫米，MOTIVATE 1组为54; MOTIVATE 2组分别增加122和128每立方毫米，MOTIVATE 2组为69;每项研究中两项比较的P<0.001）。各组不良事件的发生率相似。与安慰剂相比，Maraviroc在既往接受OBT治疗的R5 HIV-1患者中，在48周时对HIV-1的抑制作用显著更强，CD 4细胞计数增加更大。（ClinicalTrials.gov编号，NCT 00098306和NCT 00098722。）
CC chemokine receptor 5 antagonists are a new class of antiretroviral agents. We conducted two double-blind, placebo-controlled, phase 3 studies — Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 — with patients who had R5 human immunodeficiency virus type 1 (HIV-1) only. They had been treated with or had resistance to three antiretroviral-drug classes and had HIV-1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy (OBT) based on treatment history and drug-resistance testing. Safety and efficacy were assessed after 48 weeks. A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater with maraviroc than with placebo: −1.66 and −1.82 log10 copies per milliliter with the once-daily and twice-daily regimens, respectively, versus −0.80 with placebo in MOTIVATE 1, and −1.72 and −1.87 log10 copies per milliliter, respectively, versus −0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P<0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo (increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P<0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups. Maraviroc, as compared with placebo, resulted in significantly greater suppression of HIV-1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV-1 who were receiving OBT. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)