TABLE 4.
Activity of UIC-94017 against HIV-1 clinical isolates in PHA-PBMCsa
| Virus | IC50 (μM)
|
||||||
|---|---|---|---|---|---|---|---|
| AZT | SQV | APV | IDV | NFV | RTV | UIC-94017 | |
| HIV-1ERS104pre (wild-type X4) | 0.004 ± 0.002 | 0.010 ± 0.004 | 0.023 ± 0.005 | 0.018 ± 0.004 | 0.019 ± 0.002 | 0.027 ± 0.009 | 0.003 ± 0.0003 |
| HIV-1MOKW (wild-type R5) | 0.016 ± 0.009 | 0.004 ± 0.001 | 0.011 ± 0.002 | 0.018 ± 0.003 | 0.033 ± 0.008 | 0.032 ± 0.008 | 0.003 ± 0.0005 |
| HIV-1TM (MDR X4) | 0.73 ± 0.29 (183) | 0.23 ± 0.02 (23) | 0.39 ± 0.11 (17) | >1 (>56) | 0.54 ± 0.01 (28) | >1 (>37) | 0.004 ± 0.0008 (1) |
| HIV-1MM (MDR R5) | 0.37 ± 0.07 (93) | 0.30 ± 0.04 (30) | 0.34 ± 0.16 (15) | >1 (>56) | >1 (>53) | >1 (>37) | 0.02 ± 0.009 (7) |
| HIV-1JSL (MDR R5) | 0.08 ± 0.03 (20) | 0.35 ± 0.16 (35) | 0.75 ± 0.07 (33) | >1 (>56) | >1 (>53) | >1 (>37) | 0.029 ± 0.007 (10) |
| HIV-1A (MDR X4) | ND | 0.14 ± 0.06 (14) | 0.16 ± 0.05 (7) | >1 (>56) | 0.36 ± 0.10 (19) | >1 (>37) | 0.004 ± 0.0004 (1) |
| HIV-1B (MDR X4) | ND | 0.31 ± 0.01 (31) | 0.34 ± 0.01 (15) | >1 (>56) | >1 (>53) | >1 (>37) | 0.013 ± 0.006 (4) |
| HIV-1C (MDR X4) | ND | 0.037 ± 0.001 (4) | 0.28 ± 0.13 (12) | >1 (>56) | 0.44 ± 0.02 (23) | >1 (>37) | 0.003 ± 0.0006 (1) |
| HIV-1G (MDR X4) | ND | 0.029 ± 0.001 (3) | 0.25 ± 0.11 (11) | 0.39 ± 0.05 (22) | 0.32 ± 0.06 (17) | 0.44 ± 0.19 (16) | 0.004 ± 0.001 (1) |
The amino acid substitutions identified in the protease-encoding region of HIV-1ERS104pre, HIV-1TM, HIV-1MM, HIV-1JSL, HIV-1A, HIV-1B, HIV-1C, and HIV-1G compared to the consensus type B sequence cited from the Los Alamos database include L63P; L10I, K14R, R41K, M46L, I54V, L63P, A71V, V82A, L90M, and I93L; L10I, K43T, M46L, I54V, L63P, A71V, V82A, L90M, and Q92K; L10I, L24I, L33F, E35D, M36I, N37S, M46L, I54V, R57K, I62V, L63P, A71V, G73S, and V82A; L10I, I15V, E35D, N37E, K45R, I54V, L63P, A71V, V82T, L90M, I93L, and C95F, L10I, K14R, L33I, M36I, M46I, F53I, K55R, I62V, L63P, A71V, G73S, V82A, L90M, and I93L; L10I, I15V, K20R, L24I, M36I, M46L, I54V, I62V, L63P, K70O, V82A, and L89M; and L10I, V11I, T12E, I15V, L19I, R41K, M46L, L63P, A71T, V82A, and L90M, respectively. HIV-1MOKW was confirmed to lack any known drug resistance-associated amino acid substitutions. The IC50s were determined by using PHA-PBMCs as target cells and the inhibition of p24 Gag protein production as an endpoint. All values were determined in triplicate, and those shown are derived from the results of three independent experiments. Numbers in parentheses represent the fold changes in IC50s for each isolate compared to the IC50s for HIV-1ERS104pre. MDR, multidrug resistant; ND, not determined.