在初治 HIV-1 感染患者中，48 周时利匹韦林（TMC278）与依非韦伦的疗效和安全性：来自 3 期双盲随机 ECHO 和 THRIVE 试验的汇总结果。

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

机构信息

Community Research Initiative of New England, Boston, MA, USA.

出版信息

J Acquir Immune Defic Syndr. 2012 May 1;60(1):33-42. doi: 10.1097/QAI.0b013e31824d006e.

DOI:10.1097/QAI.0b013e31824d006e

PMID:22343174

Abstract

BACKGROUND

Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz.

METHODS

Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48. The pooled data set enabled analyses of subgroups and predictors of response/virologic failure.

RESULTS

Confirmed responses were 84% (rilpivirine) and 82% (efavirenz). The difference in response rates (95% confidence interval) was 2.0% (-2.0% to 6.0%). The incidence of virologic failure was 9% (rilpivirine) versus 5% (efavirenz). Responses in ITT-TLOVR and ITT-snapshot analyses were consistent. Responses were similar for rilpivirine and efavirenz by background regimen, gender, race and clade. Suboptimal adherence and higher baseline viral load resulted in lower responses, higher virologic failure, and development of resistance in both groups; the effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities.

CONCLUSIONS

At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.

摘要

背景

比较利匹韦林（TMC278）和依非韦伦的 3 期、双盲、双模拟 ECHO 和 THRIVE 试验的汇总分析。

方法

未经治疗的 HIV-1 感染成人按 1:1 随机分配至利匹韦林 25mg 每日 1 次或依非韦伦 600mg 每日 1 次，联合背景富马酸替诺福韦二吡呋酯/恩曲他滨（TDF/FTC）（ECHO）或 TDF/FTC、齐多夫定/拉米夫定或阿巴卡韦/拉米夫定（THRIVE）。主要终点为第 48 周时确认的应答[病毒载量＜50 拷贝/毫升；意向治疗时间至病毒学应答失败（ITT-TLOVR）算法]。汇总数据集可用于分析应答/病毒学失败的亚组和预测因素。

结果

确认的应答率分别为 84%（利匹韦林）和 82%（依非韦伦）。应答率的差异（95%置信区间）为 2.0%（-2.0%至 6.0%）。病毒学失败的发生率分别为 9%（利匹韦林）和 5%（依非韦伦）。ITT-TLOVR 和 ITT 快照分析的应答结果一致。利匹韦林和依非韦伦在背景治疗方案、性别、种族和谱系方面的应答相似。两组中，依从性欠佳和较高的基线病毒载量导致应答率较低、病毒学失败率较高以及耐药性的发展；依非韦伦的影响更为明显。两组的 CD4 细胞计数随时间增加。与依非韦伦相比，利匹韦林导致的不良反应导致停药的发生率较低（分别为 3%和 8%）、治疗相关的 2-4 级不良反应发生率较低（分别为 16%和 31%）、皮疹发生率较低（分别为 3%和 14%）、头晕发生率较低（分别为 8%和 26%）、异常梦境/梦魇发生率较低（分别为 8%和 13%）以及 2-4 级血脂异常发生率较低。