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在DRIVE-FORWARD和DRIVE-AHEAD第三阶段临床试验中,通过第192周确定了多拉维林耐药性模式

Chloe Orkin¹, Daniel R Kuritzkes², Christine Katlama³

¹Queen Mary University of London, London, UK.

Journal of acquired immune deficiency syndromes (1999)

|October 23, 2025

概括

对新型HIV-1 NNRTI多拉维林的耐药性在3期试验中不常见. 观察到的与耐药性相关的突变与较旧的NNRTI不同,表明多拉维林是NNRTI.

科学领域:

病毒学病毒学
传染性疾病传染性疾病
药理学药理学是指药理学的学科.

背景情况:

多拉维林是一种非核类逆转录酶抑制剂 (NNRTI),旨在克服与较旧的NNRTI常见的耐药性问题.
像K103N,Y181C和G190A这样的特定耐药性突变往往限制了以前的NNRTI的疗效.
了解多拉维林的耐药性概况对于其在HIV-1治疗方案中的有效使用至关重要.

研究的目的:

评估对多拉维林的基因型和表型耐药性的发展.
在3期DRIVE-FORWARD和DRIVE-AHEAD研究中,通过192周评估耐药性.
将多拉维林的抗药性模式与其他NNRTI的抗药性模式进行比较.

主要方法:

第三阶段,随机,双盲研究 (前进驱动和前进驱动) 在未经治疗的HIV-1感染成年人中进行.
参与者接受了多拉维林或比较剂 (达鲁纳维尔/里托纳维尔或埃法维伦兹) 96周,随后是开放式多拉维林延期.
对具有病毒学失败或停止治疗和可检测的HIV-1RNA的参与者进行了耐药性测试.

主要成果:

发生多拉维林耐药性并不常见:基因型耐药性检测到1.3%的参与者,表型耐药性检测到1.0%的参与者.
抗药性主要在治疗的前48周内出现.
观察到的与多拉维林耐药性相关的突变 (例如V106A/I/M,F227C) 与常见的NNRTI突变 (K103N,Y181C,G190A) 不同.

结论:

多拉维林在192周的时间内在未接受治疗的HIV-1患者中显示出耐药性发展的低率.
多拉维林的耐药性概况与较旧的NNRTI有显著的差异,这表明它对常见的NNRTI耐药性突变具有保留的活性.
这些发现支持多拉维林作为艾滋病毒-1管理的有效选择,特别是关于耐药性的作用.

关键词:

艾滋病病毒-1 艾滋病病毒-1 没有NNRTI,没有NRTI.临床试验临床试验临床试验临床试验临床试验多拉维林 (Doravirine) 是一种电阻的电阻是指电阻的电阻病毒学失败病毒学失败

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