Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143

Mathieu Métifiot, Nick Vandegraaff, Kasthuraiah Maddali, Alena Naumova, Xuemin Zhang, David Rhodes, Christophe Marchand, Yves Pommier

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69 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1175-1178
Number of pages4
JournalAIDS
Volume25
Issue number9
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

Keywords

  • elvitegravir
  • HIV-1
  • integrase inhibitor
  • integrase resistance
  • raltegravir

Cite this

Métifiot, M., Vandegraaff, N., Maddali, K., Naumova, A., Zhang, X., Rhodes, D., Marchand, C., & Pommier, Y. (2011). Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143. AIDS, 25(9), 1175-1178. https://doi.org/10.1097/QAD.0b013e3283473599