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转变范式:依曲韦林的耐药谱

Shifting paradigms: the resistance profile of etravirine.

作者信息

Geretti Anna Maria

机构信息

Department of Virology, Royal Free Hospital and Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK.

出版信息

J Antimicrob Chemother. 2008 Oct;62(4):643-7. doi: 10.1093/jac/dkn248. Epub 2008 Jun 19.

Abstract

The raised genetic barrier of etravirine relative to first-generation compounds indicates that it may now be possible to sequence drugs within the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. Available evidence from clinical trials provides guidance for the use of etravirine in NNRTI-experienced persons, with sustained virological suppression demonstrated in combination with other active drugs in the background regimen, most commonly including a ritonavir-boosted protease inhibitor with or without enfuvirtide. Cross-resistance occurs however, and the drug is vulnerable to loss of activity in the absence of a supportive background regimen. In order to optimize the use of etravirine in clinical practice, it is important to understand how current predictors of virological activity in NNRTI-experienced persons were developed, how they can be applied, and the adjustments and improvements they require.

摘要

依曲韦林相对于第一代化合物的遗传屏障提高,这表明现在有可能对非核苷类逆转录酶抑制剂(NNRTI)类别内的药物进行排序。来自临床试验的现有证据为在有NNRTI治疗经验的人群中使用依曲韦林提供了指导,在背景治疗方案中与其他活性药物联合使用时可实现持续的病毒学抑制,最常见的是包括一种利托那韦增强的蛋白酶抑制剂,有或没有恩夫韦肽。然而,会出现交叉耐药,并且在没有支持性背景治疗方案的情况下,该药物容易失去活性。为了在临床实践中优化依曲韦林的使用,了解有NNRTI治疗经验的人群中当前病毒学活性预测指标是如何制定的、如何应用以及它们需要哪些调整和改进非常重要。

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