Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143

• DOI: 10.1097/qad.0b013e3283473599
• Publication Date: 2011-04-19T10:26:38Z
• Authors: Mathieu Métifiot; Nick Vandegraaff; Kasthuraiah Maddali; Alena Naumova; Xuemin Zhang; David Rhodes; Christophe Marchand; Yves Pommier
• Keywords: Elvitegravir; Raltegravir; Integrase inhibitor

Objective: In this study, we characterized elvitegravir activity in the context of raltegravir resistance mutations. Design: Using site-directed mutagenesis, generated recombinant integrase proteins and viruses harboring mutation to assess biochemical cellular presence such mutants. Methods: Recombinant were used gel-based assays. Antiviral data obtained with reporter a single-round infection using luciferase-based assay. Results: Although main pathways involving mutations at position 148 155 confer cross-resistance elvitegravir, remains fully active against Y143R mutant virus particles. Conclusion: addition favorable pharmacokinetics compared raltegravir, our findings provide rationale for patients failing because Y143.