Department of Infectious Diseases, Saint-Louis Hospital and University of Paris Diderot, Paris, France.
Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.
Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine.
We did a phase 3, randomised, double-blind, double-dummy, active-controlled trial, in patients infected with HIV-1 who were treatment-naive. The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater, and viral sensitivity to all study drugs. Our trial was done at 112 sites across 21 countries. Patients were randomly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz, each with tenofovir-disoproxil-fumarate and emtricitabine. Our primary objective was to show non-inferiority (12% margin) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response (viral load <50 copies per mL intention-to-treat time-to-loss-of-virological-response [ITT-TLOVR] algorithm) at week 48. Our primary analysis was by intention-to-treat. We also used logistic regression to adjust for baseline viral load. This trial is registered with ClinicalTrials.gov, number NCT00540449.
346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with 287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was -0.4 (95% CI -5.9 to 5.2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11%vs 4% by ITT-TLOVR). Grade 2-4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p<0.0001), discontinuations due to adverse events (eight [2%] on rilpivirine vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma lipids were significantly lower with rilpivirine.
Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile.
Tibotec.
依非韦伦联合替诺福韦酯和恩曲他滨是治疗初治 HIV-1 感染者的首选抗逆转录病毒方案。利匹韦林是一种新型非核苷类逆转录酶抑制剂，在两项联合使用两种核苷/核苷酸逆转录酶抑制剂的 2b 期试验中显示出与依非韦伦相似的抗病毒疗效。我们旨在评估利匹韦林与依非韦伦在联合使用替诺福韦酯和恩曲他滨时的疗效、安全性和耐受性。
我们进行了一项 3 期、随机、双盲、双模拟、阳性对照试验，纳入了未经治疗的 HIV-1 感染患者。患者年龄在 18 岁及以上，筛选时血浆病毒载量为 5000 拷贝/ml 或以上，对所有研究药物均具有病毒敏感性。我们的试验在 21 个国家的 112 个地点进行。患者通过计算机生成的交互式网络响应系统随机分配接受每日一次 25mg 利匹韦林或每日一次 600mg 依非韦伦，均与替诺福韦酯和恩曲他滨联合使用。我们的主要目标是证明利匹韦林在第 48 周时的确认应答率（病毒载量<50 拷贝/ml 意向治疗时间病毒学应答丢失[ITT-TLOVR]算法）方面不劣于依非韦伦（12%的差值）。我们的主要分析是基于意向治疗。我们还使用逻辑回归来调整基线病毒载量。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00540449。
346 名患者被随机分配接受利匹韦林治疗，344 名患者接受依非韦伦治疗，并且至少接受了一剂研究药物，在第 48 周时，分别有 287（83%）和 285（83%）名患者有确认应答。来自逻辑回归模型的应答百分比差异的点估计值为-0.4（95%CI-5.9 至 5.2），证实了 12%差值的非劣效性（主要终点）。病毒学失败的发生率为 13%（利匹韦林）与 6%（依非韦伦；按 ITT-TLOVR 为 11%与 4%）。2-4 级不良事件（利匹韦林组 55[16%]例，依非韦伦组 108[31%]例，p<0.0001）、因不良事件停药（利匹韦林组 8[2%]例，依非韦伦组 27[8%]例）、皮疹、头晕和异常梦境或噩梦在依非韦伦组更为常见。利匹韦林组的血浆脂质升高明显较低。
利匹韦林与依非韦伦相比显示出非劣效疗效，但病毒学失败率更高，但安全性和耐受性更好。
蒂博泰克。
