临床分离株中HIV-1整合酶L74F和V75I突变对第二代整合酶链转移抑制剂耐药性的影响
Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.
作者信息
Hachiya Atsuko, Kirby Karen A, Ido Yoko, Shigemi Urara, Matsuda Masakazu, Okazaki Reiko, Imamura Junji, Sarafianos Stefan G, Yokomaku Yoshiyuki, Iwatani Yasumasa
机构信息
Department of Infectious Disease and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan
Division of Biological Information Analysis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
出版信息
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00315-17. Print 2017 Aug.
Abstract
A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.
摘要
在一例基于raltegravir的治疗方案出现病毒学失败的临床病例中，发现了一种新的HIV-1整合酶突变模式L74F V75I，该模式赋予了对第一代整合酶链转移抑制剂（INSTIs）的耐药性。将L74F V75I与N155H或G140S Q148H组合，可使对第二代INSTIs多替拉韦（分别增加>385倍和100倍）和卡博特韦（分别增加153倍和197倍）的耐药水平提高。这些发现对于开发准确的INSTI耐药性解释系统以及下一代INSTIs的合理设计具有重要意义。
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