In the first report of in vitro selection under DTG pressure conducted in primary human cells, the R263K substitution in integrase was identified through culture selection after 20 weeks as a DTG resistance-associated mutation . Furthermore, in these selection experiments, S153Y and S153T substitutions were observed in combination with R263K in one subtype B and in one subtype C virus, respectively . In the study of Quashie et al., site-directed mutagenesis analysis showed that R263K did confer very low-level resistance to DTG (Fold Change (FC) = 1.06), a slight increased for EVG (FC = 1.75) and no change for RAL (FC = 0.63) . More recently, it has been shown that in both single and multiple rounds of HIV-1 infections, bictegravir (BIC) and cabotegravir (CAB), two INIs currently under development, remained active against R263K mutant .