第 96 周时，在 ECHO 和 THRIVE 这两项 3 期、随机、双盲临床试验中，对基线病毒载量≤100000 拷贝/毫升的 HIV-1 感染患者进行利匹韦林或依非韦伦分析。

Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials.

机构信息

Department of Infectious Diseases, Saint Louis Hospital-APHP, INSERM U941 and University of Paris Diderot, Paris, France.

出版信息

HIV Med. 2014 Jan;15(1):57-62. doi: 10.1111/hiv.12071. Epub 2013 Aug 28.

DOI:10.1111/hiv.12071

PMID:23980523

Abstract

OBJECTIVES

These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.

METHODS

ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen. Response rate (the percentage of patients with VL < 50 copies/mL, using an intent-to-treat-population, time-to-loss-of-virological-response algorithm), virological failure (VF), resistance development, safety and tolerability were evaluated.

RESULTS

Baseline characteristics were comparable between the rilpivirine (n = 368) and efavirenz (n = 329) groups. At week 96, response rates [84% for rilpivirine vs. 80% for efavirenz; difference 4.0%; 95% confidence interval (CI) -1.7% to 9.7%] and incidences of VF for the resistance analysis (VFres) (8% for rilpivirine vs. 6% for efavirenz; P = 0.46) were similar in the two groups. Among patients with VFres , a comparable proportion in each group developed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). Among those with VFres , more patients in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs, mostly M184I/V. The mean (95% CI) CD4 cell count increased from baseline to week 96 by 224 (208-240) cells/μL in the rilpivirine group and by 206 (188-225) cells/μL in the efavirenz group. Treatment-related grade 2-4 overall adverse events, any rash and dizziness were less frequent for rilpivirine than for efavirenz (P < 0.0001).

CONCLUSIONS

Rilpivirine demonstrated antiviral efficacy similar to that of efavirenz in antiretroviral treatment-naïve adults with baseline VL ≤ 100 000 copies/mL over 96 weeks. Frequencies of VFres and emergent NNRTI RAMs in each group were similar. More patients with VFres in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs (mostly M184I/V). Rilpivirine had a more favourable safety/tolerability profile than efavirenz.

摘要

目的

这些 96 周的 ECHO/THRIVE 汇总分析评估了病毒载量（VL）≤100000 HIV-1 RNA 拷贝/ml 的初治、HIV-1 感染的成年人接受利匹韦林或依非韦伦治疗的数据。

方法

ECHO 和 THRIVE 是两项 3 期、随机、双盲试验。患者接受利匹韦林 25mg 每日 1 次（qd）或依非韦伦 600mg qd，联合固定（ECHO）或研究者选择（THRIVE）核苷/核苷酸逆转录酶抑制剂（N[t]RTI）背景方案。使用意向治疗人群、病毒学应答丢失时间算法，评估应答率（VL<50 拷贝/ml 的患者百分比）、病毒学失败（VF）、耐药性发展、安全性和耐受性。

结果

利匹韦林组（n=368）和依非韦伦组（n=329）的基线特征相似。96 周时，应答率[利匹韦林组 84% vs. 依非韦伦组 80%；差异 4.0%；95%置信区间（CI）-1.7%至 9.7%]和耐药分析的病毒学失败率（VFres）[利匹韦林组 8% vs. 依非韦伦组 6%；P=0.46]相似。在 VFres 患者中，每组中出现非核苷类逆转录酶抑制剂（NNRTI）耐药相关突变（RAMs）的比例相似。在 VFres 患者中，利匹韦林组比依非韦伦组更多的患者出现 N[t]RTI RAMs，主要是 M184I/V。利匹韦林组从基线到 96 周时的平均（95%CI）CD4 细胞计数增加了 224（208-240）个/μL，依非韦伦组增加了 206（188-225）个/μL。利匹韦林组与依非韦伦组相比，治疗相关的所有级别不良事件、皮疹和头晕的总发生率较低（P<0.0001）。

结论

利匹韦林在基线 VL≤100000 拷贝/ml 的初治成人中，96 周的抗病毒疗效与依非韦伦相似。两组的 VFres 和新发 NNRTI RAMs 发生率相似。在 VFres 患者中，利匹韦林组比依非韦伦组出现 N[t]RTI RAMs（主要是 M184I/V）的患者更多。利匹韦林的安全性/耐受性比依非韦伦更优。