Nelson M R, Elion R A, Cohen C J, Mills A, Hodder S L, Segal-Maurer S, Bloch M, Garner W, Guyer B, Williams S, Chuck S, Vanveggel S, Deckx H, Stevens M
Chelsea and Westminster Hospital, London, UK SW10 9NH.
HIV Clin Trials. 2013 May-Jun;14(3):81-91. doi: 10.1310/hct1403-81.
Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies.
ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated.
At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities.
The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.
在两项3期研究的汇总数据中，对1096名接受恩曲他滨/替诺福韦酯（FTC/TDF）治疗的受试者进行亚组分析，比较非核苷类逆转录酶抑制剂（NNRTI）利匹韦林（RPV）与依非韦伦（EFV）在第96周时的疗效和安全性。
ECHO和THRIVE是两项双盲、双模拟、随机、活性对照、非劣效性3期研究，在初治的成年抗逆转录病毒受试者中比较RPV与EFV加两种核苷类逆转录酶抑制剂（NRTIs）的疗效。主要和次要终点分别是在第48周和第96周时，采用意向性分析（ITT-TLOVR），HIV-1 RNA<50拷贝/mL的受试者比例。同时还评估了安全性、耐受性、免疫反应、依从性水平及其他指标。
在第48周时，确立了RPV+FTC/TDF相对于EFV+FTC/TDF的非劣效性疗效，在第96周时，RPV+FTC/TDF仍保持非劣效（两组总体缓解率均为77%）。至第96周，RPV+FTC/TDF组的病毒学失败率更高，在随访的第二年，病毒学失败和耐药突变的发生率较低且相似。RPV+FTC/TDF治疗导致的因不良事件停药率较低，包括头晕、异常梦境/噩梦、皮疹和血脂异常等2-4级不良事件。
ECHO和THRIVE研究的汇总分析表明，RPV+FTC/TDF在实现病毒学反应方面具有非劣效性，且在96周内，相对于EFV+FTC/TDF具有安全性和耐受性优势。RPV+FTC/TDF组较高的病毒学失败率与EFV+FTC/TDF组因不良事件导致的较高停药率相平衡。
