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.
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.
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