Table 2.

Comparison of the antiviral activity of 35a and other PIs against multidrug resistant clinical isolates in PHA-PBMs cells

Virus	EC50 (μM)
	35a	ATV	LPV	DRV
HIV-1ERS104pre (X4)	0.0019 ± 0.0015	0.0027 ± 0.0006	0.031 ± 0.004	0.004 ± 0.001
HIV-1MDR/B (X4)	0.0145 ± 0.0001 (8)	0.470 ± 0.007 (174)	>1 (>32)	0.034 ± 0.008 (9)
HIV-1MDR/C (X4)	0.0037 ± 0.0018 (2)	0.039 ± 0.003 (14)	0.437 ± 0.004 (14)	0.009 ± 0.005 (2)
HIV-1MDR/G (X4)	0.0026 ± 0.0004 (1)	0.019 ± 0.008 (7)	0.181 ± 0.023 (6)	0.026 ± 0.009 (7)
HIV-1MDR/TM (X4)	0.0275 ± 0.0055 (14)	0.075 ± 0.003 (28)	0.423 ± 0.082 (14)	0.022 ± 0.015 (6)
HIV-1MDR/MM (R5)	0.0050 ± 0.0023 (3)	0.205 ± 0.024 (76)	0.762 ± 0.115 (25)	0.017 ± 0.005 (4)
HIV-1MDR/JSL (R5)	0.0275 ± 0.0009 (14)	0.293 ± 0.099 (109)	>1 (>32)	0.023 ± 0.005 (6)

The amino acid substitutions identified in the protease-encoding region of HIV-1_ERS104pre, HIV-1_B, HIV-1_C, HIV-1_G, HIV-1_TM, HIV-1_MM, HIV-1_JSL compared to the consensus type B sequence cited from the Los Alamos database include L63P; L10I, K14R, L33I, M36I, M46I, F53I, K55R, I62V, L63P, A71V, G73S, V82A, L90M, I93L; L10I, I15V, K20R, L24I, M36I, M46L, I54V, I62V, L63P, K70Q, V82A, L89M; L10I, V11I, T12E, I15V, L19I, R41K, M46L, L63P, A71T, V82A, L90M; L10I, K14R, R41K, M46L, I54V, L63P, A71V, V82A, L90M; I93L; L10I, K43T, M46L, I54V, L63P, A71V, V82A, L90M, Q92K; and L10I, L24I, I33F, E35D, M36I, N37S, M46L, I54V, R57K, I62V, L63P, A71V, G73S, V82A, respectively. HIV-1_ERS104pre served as a source of wild-type HIV-1. The EC₅₀ values were determined by using PHA-PBMs as target cells and the inhibition of p24 Gag protein production by each drug was used as an endpoint. The numbers in parentheses represent the fold changes of EC₅₀ values for each isolate compared to the EC₅₀ values for wild-type HIV-1_ERS104pre. All assays were conducted in duplicate, and the data shown represent mean values (± 1 standard deviations) derived from the results of two or three independent experiments.