核苷类药物预处理患者中茚地那韦强化与非强化联合齐多夫定和拉米夫定治疗：一项随访112周的随机、开放标签试验（HIV-NAT 005）

Boosted versus unboosted indinavir with zidovudine and lamivudine in nucleoside pre-treated patients: a randomized, open-label trial with 112 weeks of follow-up (HIV-NAT 005).

作者信息

Boyd Mark A, Srasuebkul Preeyaporn, Khongphattanayothin Mana, Ruxrungtham Kiat, Hassink Elly A M, Duncombe Christopher J, Ubolyam Sasiwimol, Burger David M, Reiss Peter, Stek Michael, Lange Joep, Cooper David A, Phanuphak Praphan

机构信息

The HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

出版信息

Antivir Ther. 2006;11(2):223-32.

PMID:16640103

Abstract

INTRODUCTION

The use of HIV protease inhibitors (PIs) in a ritonavir (RTV)-boosted form is now common. However, randomized data comparing boosted with unboosted PI strategies are scarce.

METHODS

This randomized, open-label trial compared indinavir (IDV) 800 mg three times daily with IDV/RTV 800/100 mg twice daily, both given with zidovudine (AZT)/lamivudine (3TC) twice daily in individuals with at least 3 months previous AZT experience. The primary endpoint was the time-weighted average change in HIV RNA from baseline. Designed as a 48-week study, follow-up continued until week 112. Primary analysis is by intention to treat.

RESULTS

One hundred and three patients commenced therapy and are included in the analysis. Patients had a median of 29 months past nucleoside reverse transcriptase inhibitor (NRTI) exposure. Baseline median (interquartile range) log10 HIV RNA was 4.0 (3.3-4.5) and CD4+ T-cell count 166 (40-323) cells/microl. After 112-weeks of study there was no significant difference observed between arms in the mean (SD) change in time-weighted average HIV RNA from baseline (-1.6 [1.1] HIV RNA copies/week/ml three times daily arm; -1.4 [1.1] HIV RNA copies/week/ml twice daily arm; P = 0.3). Both arms were associated with substantial toxicity expressed as serious adverse events and study drug interruptions. The twice daily arm experienced greater dyslipidaemia. Mean (SD) changes in time-weighted CD4+ T-cell count from baseline were similar [88 (84) cells/week/microl three times daily arm; 70 [109] cells/week/microl twice daily arm; P = 0.3).

CONCLUSIONS

RTV-boosted IDV 800/100 mg twice daily demonstrated comparable efficacy to unboosted IDV 800 mg three times daily dosing. Both regimens were associated with substantial toxicity. Use of lower doses of RTV-boosted IDV may result in better tolerability without loss of efficacy and warrant further research.

摘要

引言

以利托那韦（RTV）增强形式使用HIV蛋白酶抑制剂（PIs）目前很常见。然而，比较增强型与未增强型PI策略的随机数据很少。

方法

这项随机、开放标签试验比较了每日三次服用800毫克茚地那韦（IDV）与每日两次服用800/100毫克IDV/RTV，两者均与齐多夫定（AZT）/拉米夫定（3TC）每日两次联合使用，对象为至少有3个月AZT使用经验的个体。主要终点是HIV RNA相对于基线的时间加权平均变化。设计为一项为期48周的研究，随访持续至第112周。主要分析采用意向性治疗。

结果

103名患者开始治疗并纳入分析。患者接受核苷类逆转录酶抑制剂（NRTI）治疗的中位时间为29个月。基线时HIV RNA的中位对数（四分位间距）为4.0（3.3 - 4.5），CD4 + T细胞计数为166（40 - 323）个/微升。经过112周的研究，两组在HIV RNA相对于基线的时间加权平均变化均值（标准差）方面未观察到显著差异（每日三次服用组为 - 1.6 [1.1] HIV RNA拷贝/周/毫升；每日两次服用组为 - 1.4 [1.1] HIV RNA拷贝/周/毫升；P = 0.3）。两组均伴有以严重不良事件和研究药物中断表示的大量毒性。每日两次服用组血脂异常更严重。相对于基线的时间加权CD4 + T细胞计数的均值（标准差）变化相似（每日三次服用组为88 [84] 个/周/微升；每日两次服用组为70 [109] 个/周/微升；P = 0.3）。