Cross-resistance Profile of the Novel Integrase Inhibitor Dolutegravir (S/GSK1349572) Using Clonal Viral Variants Selected in Patients Failing Raltegravir
Cross-resistance Profile of the Novel Integrase Inhibitor Dolutegravir (S/GSK1349572) Using Clonal Viral Variants Selected in Patients Failing Raltegravir
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DOI：
10.1093/infdis/jir636
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Clementi, Massimo
中科院分区：
文献类型：
--
作者：
Canducci, Filippo;Ceresola, Elisa R.;Clementi, Massimo
新型整合酶抑制剂正处于高级临床开发阶段，需要交叉耐药数据来考虑在这类抗逆转录病毒药物中计划序贯使用的可能性。对从11例既往含雷特格韦治疗失败的患者中获得的11种野生型和27种完全复制的重组病毒进行了体外表型测定。多鲁特韦在体外对143和155位突变的病毒保持活性。然而，突变Q148R与继发突变相关的病毒和组合Q148H + G140S与体外对度鲁特韦的敏感性水平降低相关。
Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H + G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.