在治疗经验丰富的患者中，作为优化联合抗逆转录病毒疗法的一部分，单独使用利托那韦或与其他增效蛋白酶抑制剂联合使用增效替拉那韦的药代动力学、安全性和疗效（BI研究1182.51）

Pharmacokinetics, safety, and efficacy of tipranavir boosted with ritonavir alone or in combination with other boosted protease inhibitors as part of optimized combination antiretroviral therapy in highly treatment-experienced patients (BI Study 1182.51).

作者信息

Walmsley Sharon L, Katlama Christine, Lazzarin Adriano, Arestéh Keikawus, Pierone Gerald, Blick Gary, Johnson Margaret, Meier Ulrich, MacGregor Thomas R, Leith Johnathan G

机构信息

Division of Clinical Investigation and Human Physiology, University of Toronto, Toronto, ON, Canada.

出版信息

J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):429-40. doi: 10.1097/QAI.0b013e318160a529.

DOI:10.1097/QAI.0b013e318160a529

PMID:18176328

Abstract

BACKGROUND

Given the limited treatment options for patients with high-level resistance, antiretroviral (ARV) regimens based on concomitant use of 2 ritonavir (RTV)-boosted protease inhibitors (PIs) were considered a therapeutic option.

METHODS

Boehringer Ingelheim (BI) study 1182.51 examined the pharmacokinetic profile, safety, and efficacy of RTV-boosted tipranavir (TPV/r), alone and in combination with comparator PIs (CPIs) in 315 triple-class-experienced, HIV-infected patients.

RESULTS

Two weeks after single PI therapy, the addition of TPV/r reduced plasma trough levels 52%, 80%, and 56% for lopinavir (LPV), saquinavir (SQV), and amprenavir (APV) recipients, respectively. After 2 weeks, a TPV/r-only regimen reduced HIV viral load (VL) by a median of 1.06 log(10) copies/mL. VL reductions at 2 weeks between single-boosted CPIs were difficult to compare, because the numbers of patients maintaining their previous failing PI after randomization were different. At week 4, patients initiating treatment with TPV-containing regimens sustained VL reduction (median decrease of 1.27 log(10) copies/mL). Patients adding TPV to regimens at week 2 achieved median reductions from a baseline of 1.19 log(10), 0.96 log(10), and 1.12 log(10) copies/mL at week 4 in dual-boosted LPV, SQV, and APV groups, respectively. At 24 weeks, VL reductions (median: -0.24 to -0.47 log(10) copies/mL) were comparable between treatment groups.

CONCLUSIONS

The efficacy of a dual PI regimen depended on the presence of TPV, with additional recycled CPIs having limited activity, even in drug-resistant patient populations with plasma trough concentrations regarded as likely to be adequate in this study. No clear guidelines exist about ARV plasma trough concentrations in treatment-experienced patients, however.

摘要

背景

鉴于对具有高水平耐药性的患者治疗选择有限，基于同时使用两种利托那韦（RTV）增强型蛋白酶抑制剂（PIs）的抗逆转录病毒（ARV）方案被视为一种治疗选择。

方法

勃林格殷格翰（BI）研究1182.51在315例有三类药物治疗经验的HIV感染患者中，单独及与对照蛋白酶抑制剂（CPIs）联合使用时，研究了RTV增强型替拉那韦（TPV/r）的药代动力学特征、安全性和疗效。

结果

单蛋白酶抑制剂治疗两周后，对于洛匹那韦（LPV）、沙奎那韦（SQV）和安普那韦（APV）接受者，加用TPV/r分别使血浆谷浓度降低了52%、80%和56%。两周后，仅使用TPV/r的方案使HIV病毒载量（VL）中位数降低了1.06 log(10)拷贝/毫升。单增强型CPIs在两周时的VL降低情况难以比较，因为随机分组后维持先前失败的蛋白酶抑制剂治疗的患者数量不同。在第4周，开始使用含TPV方案治疗的患者维持了VL降低（中位数降低1.27 log(10)拷贝/毫升）。在第2周将TPV添加到方案中的患者，在第4周时，双增强型LPV、SQV和APV组分别从基线水平中位数降低了1.19 log(10)、0.96 log(10)和1.12 log(10)拷贝/毫升。在24周时，各治疗组之间的VL降低情况（中位数：-0.24至-0.47 log(10)拷贝/毫升）相当。