Community Research Initiative of New England, Boston, MA 02215, USA.
Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.
The non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (TMC278; Tibotec Pharmaceuticals, County Cork, Ireland), had equivalent sustained efficacy to efavirenz in a phase 2b trial in treatment-naive patients infected with HIV-1, but fewer adverse events. We aimed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs).
We undertook a 96-week, phase 3, randomised, double-blind, double-dummy, non-inferiority trial in 98 hospitals or medical centres in 21 countries. We enrolled adults (≥18 years) not previously given antiretroviral therapy and with a screening plasma viral load of 5000 copies per mL or more and viral sensitivity to background N(t)RTIs. We randomly allocated patients (1:1) using a computer-generated interactive web-response system to receive oral rilpivirine 25 mg once daily or efavirenz 600 mg once daily; all patients received an investigator-selected regimen of background N(t)RTIs (tenofovir-disoproxil-fumarate plus emtricitabine, zidovudine plus lamivudine, or abacavir plus lamivudine). The primary outcome was non-inferiority (12% margin on logistic regression analysis) at 48 weeks in terms of confirmed response (viral load <50 copies per mL, defined by the intent-to-treat time to loss of virologic response [TLOVR] algorithm) in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00543725.
From May 22, 2008, we screened 947 patients and enrolled 340 to each group. 86% of patients (291 of 340) who received at least one dose of rilpivirine responded, compared with 82% of patients (276 of 338) who received at least one dose of efavirenz (difference 3.5% [95% CI -1.7 to 8.8]; p(non-inferiority)<0.0001). Increases in CD4 cell counts were much the same between groups. 7% of patients (24 of 340) receiving rilpivirine had a virological failure compared with 5% of patients (18 of 338) receiving efavirenz. 4% of patients (15) in the rilpivirine group and 7% (25) in the efavirenz group discontinued treatment due to adverse events. Grade 2-4 treatment-related adverse events were less common with rilpivirine (16% [54 patients]) than they were with efavirenz (31% [104]; p<0.0001), as were rash and dizziness (p<0.0001 for both) and increases in lipid levels were significantly lower with rilpivirine than they were with efavirenz (p<0.0001).
Despite a slightly increased incidence of virological failures, a favourable safety profile and non-inferior efficacy compared with efavirenz means that rilpivirine could be a new treatment option for treatment-naive patients infected with HIV-1.
Tibotec.
非核苷类逆转录酶抑制剂（NNRTI）利匹韦林（TMC278；Tibotec 制药公司，爱尔兰科克郡）在治疗初治 HIV-1 感染患者的 2b 期试验中与依非韦伦等效，但不良反应较少。我们旨在评估利匹韦林与依非韦伦在具有常见背景核苷或核苷酸逆转录酶抑制剂（N[t]RTIs）的 3 期试验中的非劣效性。
我们在 21 个国家的 98 家医院或医疗中心进行了一项为期 96 周的 3 期随机、双盲、双模拟、非劣效性试验。我们招募了未接受过抗逆转录病毒治疗且筛选时血浆病毒载量为 5000 拷贝/毫升或更高且对背景 N[t]RTIs 敏感的成年（≥18 岁）患者。我们使用计算机生成的交互式网络响应系统以 1:1 的比例随机分配患者接受每日一次口服利匹韦林 25mg 或每日一次依非韦伦 600mg；所有患者均接受背景 N[t]RTIs（富马酸替诺福韦二吡呋酯+恩曲他滨、齐多夫定+拉米夫定或阿巴卡韦+拉米夫定）的研究者选择方案。主要终点是所有至少接受一剂研究药物的患者在 48 周时的确认应答（根据意向治疗时间至病毒学应答丢失[TLOVR]算法定义的病毒载量<50 拷贝/毫升）的非劣效性（逻辑回归分析 12%的差异）。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT00543725。
从 2008 年 5 月 22 日开始筛选，我们筛选了 947 名患者，每组纳入 340 名。至少接受一剂利匹韦林治疗的患者中有 86%（291/340）有应答，而至少接受一剂依非韦伦治疗的患者中有 82%（276/338）有应答（差异为 3.5%[95%CI-1.7 至 8.8]；p（非劣效性）<0.0001）。两组之间 CD4 细胞计数的增加大致相同。与接受依非韦伦治疗的患者（5%[18/338]）相比，接受利匹韦林治疗的患者中有 7%（24/340）发生病毒学失败。与接受依非韦伦治疗的患者（7%[25/338]）相比，接受利匹韦林治疗的患者中有 4%（15 例）因不良反应而停止治疗。利匹韦林组的治疗相关不良事件（2-4 级）发生率（16%[54 例]）低于依非韦伦组（31%[104 例]）（p<0.0001），皮疹和头晕（均为 p<0.0001）以及血脂水平升高的发生率也明显低于依非韦伦组（均为 p<0.0001）。
尽管病毒学失败的发生率略有增加，但利匹韦林具有良好的安全性和与依非韦伦相当的疗效，这意味着利匹韦林可能成为治疗初治 HIV-1 感染患者的一种新的治疗选择。
Tibotec。
