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 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.