In this manuscript, we have reviewed main in vivo and in vitro knowledge about two integrase resistance-associated mutations: R263K and E157Q. R263K mutation is interesting because this mutation was selected in vivo at failure of a DTG-based regimen and only displayed a moderate increase in phenotypic resistance level . Furthermore, Mark Wainberg and his team conducted several studies regarding in vitro characteristics of R263K integrase mutants. E157Q integrase mutation is of interest too, since it is both polymorphic, with variable prevalence in INI-naïve patients depending on the viral subtype , but also selected at virological failure (VF) of a RAL-based regimen in two case reports  and described in a case report of a non virological response to a DTG-based regimen .