TABLE 2.

Activities of GRL-216 and GRL-286 against laboratory PI-resistant HIV-1 variants^a

Virus	EC50 (μM)
	SQV	NFV	APV	LPV	AZV	TPV	DRV	GRL-216	GRL-286
HIV-1NL4- 3	0.005 ± 0.002	0.045 ± 0.032	0.034 ± 0.001	0.046 ± 0.025	0.004 ± 0.0004	0.32 ± 0.07	0.003 ± 0.0006	0.005 ± 0.001	0.009 ± 0.0006
HIV-1SQV-5 μM	>1 (>200)	0.51 ± 0.081 (11)	0.18 ± 0.10 (5)	0.12 ± 0.02 (2)	0.21 ± 0.065 (53)	0.022 ± 0.009 (0.1)	0.003 ± 0.0002 (1)	0.020 ± 0.009 (4)	0.046 ± 0.021 (5)
HIV-1NFV-5 μM	0.003 ± 0.002 (1)	>1 (>22)	0.028 ± 0.005 (1)	0.037 ± 0.004 (1)	0.027 ± 0.005(7)	0.039 ± 0.041 (0.1)	0.006 ± 0.0002 (2)	0.040 ± 0.017 (8)	0.041 ± 0.006 (5)
HIV-1APV-5 μM	0.026 ± 0.010 (5)	0.30 ± 0.03 (7)	>1 (>29)	>1 (>22)	0.006 ± 0.002 (2)	0.22 ± 0.089 (0.7)	0.29 ± 0.0018 (97)	>1 (>200)	>1 (>111)
HIV-1LPV-5 μM	0.028 ± 0.007 (6)	0.32 ± 0.12 (7)	0.26 ± 0.07 (8)	>1 (>22)	0.036 ± 0.001 (9)	0.31 ± 0.030 (1)	0.025 ± 0.0066 (8)	0.035 ± 0.005 (7)	0.35 ± 0.019 (39)
HIV-1AZV-5 μM	0.031 ± 0.005 (6)	>1 (>22)	0.28 ± 0.06 (8)	>1 (>22)	>1 (>250)	0.41 ± 0.047 (1)	0.009 ± 0.0025 (3)	0.023 ± 0.005 (5)	0.030 ± 0.006 (3)

^aThe amino acid substitutions identified in the protease-encoding regions of HIV-1_{SQV-5 μM}, HIV-1_{NFV-5 μM}, HIV-1_{APV-5 μM}, HIV-1_{LPV-5 μM}, and HIV-1_{AZV-5 μM} compared to the consensus type B sequence cited from the Los Alamos database include L10I/G48V/I54V/A71V/I84V/L90 M, L10F/D30N/K45I/A71V/T74S, L10F/M46I/I50V/A71V/I84V/L90 M, L10F/M46I/I54V/V82A, and L23I/E34Q/K43I/M46I/I50L/G51A/L63P/A71V/V82A/T91A, respectively. MT-4 cells (10⁴) were exposed to 100 TCID₅₀s of each HIV-1 isolate, and inhibition of p24 Gag protein production by each drug was used as the end point. Numbers in parentheses represent the n-fold changes in the EC₅₀s for each isolate compared to the EC₅₀s for wild-type isolate HIV-1_NL4-3. All assays were conducted in duplicate or triplicate, and the data shown represent mean values (±1 standard deviation) derived from the results of three independent experiments.