title: Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir.
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.
authors: Vita-Salute San Raffaele University, Laboratory of Virology and Microbiology, Milan, Italy. canducci.filippo@hsr.it
authors: Filippo
authors: F
authors: Canducci
authors: Elisa R
authors: ER
authors: Ceresola
authors: Enzo
authors: E
authors: Boeri
authors: Vincenzo
authors: V
authors: Spagnuolo
authors: Francesca
authors: F
authors: Cossarini
authors: Antonella
authors: A
authors: Castagna
authors: Adriano
authors: A
authors: Lazzarin
authors: Massimo
authors: M
authors: Clementi
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010078:Oxazines; D010641:Phenotype; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000494:pharmacology; D000068898:Raltegravir Potassium; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000099226:Dolutegravir