De Castro Nathalie, Braun Joséphine, Charreau Isabelle, Pialoux Gilles, Cotte Laurent, Katlama Christine, Raffi François, Weiss Laurence, Meynard Jean-Luc, Yazdanpanah Yazdan, Delaugerre Constance, Madelaine-Chambrin Isabelle, Aboulker Jean-Pierre, Molina Jean-Michel
Department of Infectious Diseases, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital and University of Paris VII Denis Diderot, Paris, France.
Clin Infect Dis. 2009 Oct 15;49(8):1259-67. doi: 10.1086/605674.
Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide.
A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level >or=400 copies/mL, over 24 weeks. The secondary end points mainly involved safety.
The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (beta = 0.01%; 95% confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (beta = 1.22%; 95% confidence interval, -5.6 to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms.
A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy.
NCT00454337
在多重耐药的1型人类免疫缺陷病毒（HIV-1）感染患者中，包括恩夫韦肽在内的挽救治疗方案已显示出持续疗效。由于患者不愿接受皮下注射，雷特格韦可能是在抑制治疗方案中替代恩夫韦肽的一种选择。我们进行了一项前瞻性、随机、开放标签试验，以比较换用雷特格韦与继续使用恩夫韦肽的抗病毒疗效和安全性。
共有170例接受基于恩夫韦肽方案治疗、多重耐药HIV-1感染且血浆HIV-1 RNA水平<400拷贝/mL的患者，按1:1随机分组，分别维持使用恩夫韦肽或换用雷特格韦。主要疗效终点是在24周内病毒学失败患者的累积比例，病毒学失败定义为确诊血浆HIV-1 RNA水平≥400拷贝/mL。次要终点主要涉及安全性。
换用雷特格韦不劣于维持使用恩夫韦肽，在意向性分析中，两个治疗组的病毒学失败率均为1.2%（β=0.01%；95%置信区间，-6.7至6.8），在治疗中分析中分别为1.2%和0%（β=1.22%；95%置信区间，-5.6至8.1）。在第24周时，两组中88%-89%的患者血浆HIV-1 RNA水平<50拷贝/mL。两组的CD4细胞计数均未发生显著变化。3-4级不良事件和实验室异常情况不常见，且治疗组之间无差异。
对于接受抑制性抗逆转录病毒治疗的多重耐药HIV-1感染患者，换用雷特格韦是安全的，耐受性良好，且在病毒学方面不劣于维持使用恩夫韦肽。
NCT00454337
