Km and Ki Dataset for Selection of HIV-1 for Resistance to Fifth Generation Protease Inhibitors Reveals Two Independent Pathways to High-Level Resistance

Ki values were determined against all UMASS inhibitors (Table 1). Brackets above the bars represent significant p-values between the two groups using the unpaired t-test. Data were pooled in different ways for the following analyses: A) The Ki values against the inhibitors with the larger R1-2 moiety (n=34) were more potent against resistant proteases compared to the inhibitors with the smaller R1-1 moiety (n=35) B) Ki values for the inhibitors with the R2-2 group (n=10) showed a trend toward being more potent against the highly mutated proteases compared to the other R2 groups (n=40). C) Ki values for enzymes with the I50V mutation (n=33) showed greater resistance to the inhibitors compared to enzymes with the I84V mutation (n=22). D) The R1-2 moiety provided increased potency to enzymes with the I84V mutation (n=20) but not the I50V mutation (n=20). E) The R2-2 moiety was more potent against the enzymes with I84V mutation (n=10) compared to the enzymes with the I50V mutation (n=10). The unpaired t-test was used to assess differences in Ki values.