The cleavage of the Gag-Pol polyprotein by the viral protease (PR) is essential for the infectivity of HIV virions.Protease inhibitor (PI) therapy can give rise to resistance mutations in the protease,which is often associated with a decreased activity of the enzyme.Impaired function can be partially restored by compensatory mutations in the cleavage sites (CS),probably by providing a better substrate for the mutated,and in some cases also for the wild-type,proteases.We performed a statistical analysis on publicly available HIV sequences to detect associations between specific protease and cleavage site mutations,which might identify variations at cleavage sites as potential compensatory mutations.