Table 2.

Antiviral activity of Pis 3 and 4 against multi-drug resistant clinical isolates in PHA-PBMs (EC₅₀, μM)

Virus (phenotype)	APV	DRV	3 (GRL-04810)	4 (GRL-05010)
HIV-1ERS104pre (wild-type X4)	0.0295 ± 0.0004	0.004 ± 0.001	0.0023 ± 0.0001	0.0027 ± 0.0003
HIV-1MDR/B(X4)	0.49 ± 0.05 (15)	0.021 ± 0.001 (5)	0.014 ± 0.001 (7)	0.011 ± 0.001 (3)
HIV-1MDR/C(X4)	0.21 ± 0.02 (7)	0.005 ± 0.001 (1)	0.002 ± 0.001 (1)	0.002 ± 0.001 (1)
HIV-1MDR/G(X4)	0.31 ± 0.08 (11)	0.014 ± 0.009 (4)	0.004 ± 0.001 (2)	0.004 ± 0.001 (1)
HIV-1MDR/TM(X4)	0.328 ± 0.001 (12)	0.03 ± 0.01 (9)	0.004 ± 0.001 (2)	0.004 ± 0.001 (2)
HIV-1MDR/MM(R5)	0.630 ± 0.009 (22)	0.025 ± 0.002 (5)	0.021 ± 0.004 (10)	0.020 ± 0.0002 (7)
HIV-1MDR/JSL(R5)	0.27 ± 0.01 (9)	0.010 ± 0.001 (3)	0.002 ± 0.001 (1)	0.003 ± 0.001 (1)

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 IC₅₀ 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.