ObjectivesRelatively little is known about the development of resistance to protease inhibitors (PIs) in non-B subtypes. In subtype B viruses, L89 is commonly found at position 89 in the HIV protease (PR) gene, whereas M89 is commonly observed as a polymorphism in other subtypes. We compared the frequencies of substitutions at position 89 in PR in tissue culture selections and in clinical databases of PI-naive and PI-experienced populations.