In the SAILING randomized trial, which included cART-experienced but INI-naïve patients, selection of INI resistance at time of VF through week 24 was observed in two participants among the DTG arm (n = 354 patients). In both cases the R263K mutation was selected with a plasma viral load at failure comprised between 3 and 4 log10 c/mL . One virus displayed R263K as a single mutation and phenotypic analysis of this clinical isolate showed a FC to DTG and RAL of 1.12 and 0.96, respectively, with a reduced viral replicative capacity equal to 33% . The second virus harbored the V260I mutation added to the R263K, this double-mutant resulted in a FC to DTG and RAL of 1.93 and 1.12, respectively . The single mutant V260I did not confer DTG or RAL FC increase . In addition, R263K site-directed mutant analyses using MT4 cells in a 5-day assay with cell tier glow readout showed a FC of 2.1, 0.8 and 10.6 for DTG, RAL and EVG, respectively . A few additional VF occurred in the SAILING trial after W48 and R263K mutation was detected in one of them . In this latter, VF occurred at week 120 with a viral load of 622 c/mL and R263K was detected added to A49G and S230R integrase mutations. This accumulation of integrase mutations probably resulted from the long duration of replication under treatment, since plasma viral load was above 50 c/mL since week 96. This triple-mutant clinical isolate showed an increased DTG FC of 5.77 and a RAL FC of 2.62, with a very low viral replicative capacity of 12% .