Interactions in binding site of drug resistant protease Patient ID 6652 6665 6670 6671 6674 6678 6685 6686 6687 6689 6691 6693 6696 6706 19255 Conserved residues in Interactions observed in crystals (%) 52 52 42 52 52 52 52 52 52 52 52 52 52 52 36   ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A ASP 25A   ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B ASP 25B   ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A ASP 29A   ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B ASP 29B   ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A ASP 30A   ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B ASP 30B   GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A GLY 27A   GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B GLY 27B   GLY 48A GLY 48A ILE 50A GLY 48A GLY 48A GLY 48A ILE 50A GLY 48A GLY 48A GLY 48A GLY 48A GLY 48A GLY 48A GLY 48A GLY 48A   GLY 48B GLY 48B ILE 50B GLY 48B GLY 48B GLY 48B ILE 50B GLY 48B GLY 48B GLY 48B GLY 48B GLY 48B GLY 48B GLY 48B GLY 48B   ILE 50A ILE 50A     ILE 50A ILE 50A ILE 50A         ILE 50A ILE 50A ILE 50A ILE 50A ILE 50A ILE 50A ILE 50A   ILE 50B ILE 50B     ILE 50B ILE 50B ILE 50B         ILE 50B ILE 50B ILE 50B ILE 50B ILE 50B ILE 50B ILE 50B

Table 10: Residues in interaction with the drug of treatment 2 (second treatment to overcome drug resistance) are listed. Those highlighted in yellow are part of the critical set (see Table, Supplemental Digital Content 8, which shows the critical residues involved in ARV interactions and characterized in the crystal HIV-1 proteases from HIV-PDI database). These residues are no longer involved in the interaction with the drug of treatment 1 (Treatment which produce drug resistance).