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

Filippo Canducci, Elisa R Ceresola, Enzo Boeri, Vincenzo Spagnuolo, Francesca Cossarini, Antonella Castagna, Adriano Lazzarin, Massimo Clementi
Journal of Infectious Diseases 2011 December 1, 204 (11): 1811-5
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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