In this study of nine clinical isolates obtained from integrase inhibitor-naïve HIV-2-infected patients, the median EC₅₀ value for the new integrase inhibitor S/GSK1349572 was 0.8 nM (range 0.2-1.4), and is similar to HIV-1 reference strains. We found a seven-, 13- and 18-fold increase in EC₅₀ values to S/GSK1349572 for the HIV-2 double (T97A + Y143C; G140S + Q148R) and triple (G140T + Q148R + N155H) mutants, respectively, obtained from two raltegravir-experienced patients.