In 1994 Dr. Richman was awarded a 5 year grant with a probable extension on the basis of a merit award. The grant, "Antiviral Resistance in AIDS", proposed to address six Aims relating to drug resistance of HIV and herpesviruses, one of which was to select for and characterize resistance to HIV protease inhibitors. Dr. Deenan Pillay addressed this question while he was visiting Dr. Richman lab in 1994 on a Visiting Fogarty Award. Recent work in the field, including that of Dr. Pillay, has indicated that HIV protease can acquire multiple mutations resulting in high level resistance to inhibitors. The ability to effectively utilize protease inhibitors for sustained clinical activity may well depend upon characterizing different resistance patterns of various inhibitors, selecting combinations of inhibitors with complementary activity with regard to resistance patterns and identifying combinations of inhibitors that might force mutations with impaired replicative capacity. This proposal would permit Dr. Pillay to extend the studies initiated in Dr. Richman s lab. It would also foster a collaboration between the two labs that would introduce and develop molecular biologic and antiviral research in HIV in Dr. Pillay's New laboratory at Birmingham Public Health Laboratories.