Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development.
Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development.
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临床发育过程中参与者在参与者中确定的多韦林抵抗模式的综述。
DOI：
10.1097/qai.0000000000002496
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发表时间：
2020-12-15
期刊：
影响因子：
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通讯作者：
Asante-Appiah E
中科院分区：
文献类型：
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作者：
Martin EA;Lai MT;Ngo W;Feng M;Graham D;Hazuda DJ;Kumar S;Hwang C;Sklar P;Asante-Appiah E
多拉韦林（DOR）是一种新型非核苷类逆转录酶抑制剂（NNRTI），被批准用于治疗无已知DOR耐药相关突变的HIV-1感染患者。DOR的合理设计旨在解决与其他获批NNRTI相关的局限性，特别是来自常见NNRTI耐药相关突变体（包含K103 N、Y181 C或G190 A逆转录酶取代）的耐药性。迄今为止，已对体外研究和临床试验的数据进行了汇编，以总结DOR的耐药性特征。我们分析了体外研究和2期和3期试验的数据，以评估耐药相关突变的出现及其对DOR治疗参与者疗效的影响。与依法韦仑和利匹韦林相比，DOR在体外和体内表现出明显的耐药特征;对DOR耐药的突变病毒对依法韦仑和利匹韦林的交叉耐药有限。在临床试验中，逆转录酶中DOR耐药相关置换的发生并不常见。总体而言，观察到DOR在NNRTI中的交叉耐药极小，DOR相关耐药的发生有限。这些数据应有助于临床医生进一步了解DOR的耐药性特征，以便为患者做出适当的治疗决策。
Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of HIV-1 infection in patients with no known DOR resistance-associated mutations. DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions. Data to date from both in vitro studies and clinical trials have been compiled to summarize the resistance profile of DOR. We analyzed data from in vitro studies and phase 2 and 3 trials to assess the emergence of resistance-associated mutations and their impact on efficacy among participants treated with DOR. DOR exhibited a distinct resistance profile compared with efavirenz and rilpivirine in vitro and in vivo; mutant viruses that were resistant to DOR showed limited cross-resistance to efavirenz and rilpivirine. In clinical trials, the development of DOR resistance-associated substitutions in reverse transcriptase was uncommon. Overall, minimal cross-resistance across NNRTIs was observed for DOR and limited development of DOR-related resistance. These data should assist clinicians in further understanding the resistance profile of DOR, so appropriate treatment decisions can be made for their patients.