Cantonal Hospital, St. Gallen, Switzerland.
J Acquir Immune Defic Syndr. 2013 Feb 1;62(2):171-9. doi: 10.1097/QAI.0b013e31827a2ba2..
A 96-week clinical study was planned to estimate the antiviral activity and safety of lersivirine in treatment-naive HIV-1-infected patients.
This ongoing international, multicenter, double-blind, randomized, Phase IIb exploratory study evaluates the efficacy and safety of 2 doses of lersivirine or 1 of efavirenz, each combined with tenofovir disoproxil fumarate/emtricitabine. Patients were randomized 1:1:1 to receive lersivirine (500 or 750 mg once daily) or efavirenz (600 mg once daily), each administered with tenofovir disoproxil fumarate/emtricitabine (300 mg/200 mg, once daily). The primary endpoint is the proportion of patients with HIV-1 RNA <50 copies per milliliter (missing/discontinuation = failure) at week 48.
For the 193 patients in the study, baseline mean plasma HIV-1 RNA was 4.7 log10 copies per milliliter, and median CD4 cell count was 312 cells per cubic millimeter. At week 48, the percentage of patients with HIV-1 RNA <50 copies per milliliter was 78.5% (51/65), 78.5% (51/65), and 85.7% (54/63) in the lersivirine 500 mg, 750 mg, and efavirenz groups, respectively. CD4 cell count changes from baseline were similar across groups. Virologic failure occurred in 7 patients (11%) in each of the lersivirine groups and 3 patients (5%) in the efavirenz group. The pattern of lersivirine resistance was distinct from other nonnucleoside reverse transcriptase inhibitors. Overall incidences of all-causality treatment-related or grade 3/4 adverse events (AEs) or AE-related discontinuations were lower with lersivirine than with efavirenz, and serious AEs occurred at similar rates across treatment groups.
Both lersivirine doses showed broadly comparable efficacy to efavirenz over 48 weeks in treatment-naive patients, with different AE profiles from efavirenz.
一项为期 96 周的临床研究旨在评估利匹韦林在初治 HIV-1 感染患者中的抗病毒活性和安全性。
本研究是一项正在进行的国际性、多中心、双盲、随机、Ⅱb 期探索性研究，评估了利匹韦林 2 种剂量或依非韦伦 1 种剂量联合富马酸替诺福韦二吡呋酯/恩曲他滨的疗效和安全性。患者按 1:1:1 随机接受利匹韦林（500 或 750 mg，每日 1 次）或依非韦伦（600 mg，每日 1 次）治疗，联合富马酸替诺福韦二吡呋酯/恩曲他滨（300 mg/200 mg，每日 1 次）。主要终点为第 48 周时 HIV-1 RNA<50 拷贝/ml 的患者比例（缺失/停药=失败）。
193 例患者的基线平均血浆 HIV-1 RNA 为 4.7 log10 拷贝/ml，中位 CD4 细胞计数为 312 个/立方毫米。第 48 周时，HIV-1 RNA<50 拷贝/ml 的患者比例分别为利匹韦林 500 mg、750 mg 和依非韦伦组 78.5%（51/65）、78.5%（51/65）和 85.7%（54/63）。各组的 CD4 细胞计数从基线的变化相似。利匹韦林组各有 7 例（11%）和依非韦伦组各有 3 例（5%）患者发生病毒学失败。利匹韦林耐药模式与其他非核苷类逆转录酶抑制剂不同。利匹韦林组的全因治疗相关或 3/4 级不良事件（AE）或 AE 相关停药的总发生率低于依非韦伦组，且两组的严重 AE 发生率相似。
在初治患者中，利匹韦林两个剂量在 48 周时的疗效与依非韦伦大致相当，与依非韦伦相比，AE 谱不同。
