Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143

被引：69
|
作者：
Metifiot, Mathieu [1 ]
Vandegraaff, Nick [2 ]
Maddali, Kasthuraiah [1 ]
Naumova, Alena [1 ]
Zhang, Xuemin [1 ]
Rhodes, David [2 ]
Marchand, Christophe [1 ]
Pommier, Yves [1 ]
机构：
[1] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] Avexa Ltd, Melbourne, Vic, Australia
来源：
AIDS | 2011年 / 25卷 / 09期
关键词：
elvitegravir; HIV-1; integrase inhibitor; integrase resistance; raltegravir; HIV-1; INTEGRASE; EXPERIENCED PATIENTS; INHIBITION; PATTERNS; INTASOME; MUTANTS; VIRUS;
D O I：
10.1097/QAD.0b013e3283473599
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Objective: In this study, we characterized elvitegravir activity in the context of raltegravir resistance mutations. Design: Using site-directed mutagenesis, we generated recombinant integrase proteins and viruses harboring raltegravir resistance mutation to assess the biochemical and cellular activity of elvitegravir in the presence of such mutants. Methods: Recombinant proteins were used in gel-based assays. Antiviral data were obtained with reporter viruses in a single-round infection using a luciferase-based assay. Results: Although main raltegravir resistance pathways involving mutations at integrase position 148 and 155 confer cross-resistance to elvitegravir, elvitegravir remains fully active against the Y143R mutant integrase and virus particles. Conclusion: In addition to favorable pharmacokinetics compared to raltegravir, our findings provide the rationale for using elvitegravir in patients failing raltegravir because of the integrase mutation Y143. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
引用
收藏
页码：1175 / 1178
页数：4
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