1. Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir.
- Author
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Canducci F, Ceresola ER, Boeri E, Spagnuolo V, Cossarini F, Castagna A, Lazzarin A, and Clementi M
- Subjects
- Amino Acid Substitution genetics, HIV Infections virology, HIV Integrase genetics, HIV-1 enzymology, Humans, Inhibitory Concentration 50, Microbial Sensitivity Tests, Mutation, Oxazines, Phenotype, Piperazines, Pyridones, Pyrrolidinones pharmacology, Raltegravir Potassium, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Integrase Inhibitors pharmacology, HIV-1 drug effects, HIV-1 genetics, Heterocyclic Compounds, 3-Ring pharmacology
- Abstract
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.
- Published
- 2011
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