Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir

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 viruse...

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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 204; no. 11; p. 1811
Main Authors: Canducci, Filippo, Ceresola, Elisa R, Boeri, Enzo, Spagnuolo, Vincenzo, Cossarini, Francesca, Castagna, Antonella, Lazzarin, Adriano, Clementi, Massimo
Format: Journal Article
Language:English
Published: United States 01.12.2011
Subjects:
Amino Acid Substitution - genetics
Anti-HIV Agents - pharmacology
Drug Resistance, Viral - genetics
Heterocyclic Compounds, 3-Ring - pharmacology
HIV Infections - drug therapy
HIV Infections - virology
HIV Integrase - genetics
HIV Integrase Inhibitors - pharmacology
HIV-1 - drug effects
HIV-1 - enzymology
HIV-1 - genetics
Humans
Inhibitory Concentration 50
Microbial Sensitivity Tests
Mutation
Phenotype
Pyrrolidinones - pharmacology
Raltegravir Potassium
ISSN:1537-6613, 1537-6613
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Summary: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.
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ISSN:1537-6613
1537-6613
DOI:10.1093/infdis/jir636