It has been shown that R263K mutants display a low viral replicative capacity . Thus, several studies were conducted to identify potential secondary mutations that would restore viral replicative capacity. First studies reported on the M50I integrase polymorphism, since it was selected in culture secondary to the R263K mutation . The findings showed that M50I polymorphism in combination with R263K increased resistance to DTG in tissue culture and in biochemical assays but did not restore viral replicative capacity of the R263K mutant . Similarly, H51Y integrase mutation also emerged secondary to R263K mutation in DTG selection experiments. So, in vitro characteristics of H51Y single- and H51Y-R263K double-mutants were studied showing that the addition of H51Y to R263K increased phenotypic resistance level to DTG with a FC of 16.5, whereas H51Y alone did not confer resistance to this drug. However, the addition of H51Y is accompanied by dramatic decreases in both enzymatic activity and viral replication. So, the H51Y mutation is also not a compensatory mutation to the R263K .