TABLE 1 .
Infectious clone | Amino acid substitution(s) in PR | IC50 (mean ± SD) (nM) (fold change)a |
|||
---|---|---|---|---|---|
DRV | APVb | AZTc | RALd | ||
rHIVWT | None | 3.1 ± 0.3 | 24 ± 2 | 30 ± 9 | 4.9 ± 3.2 |
rHIVDRVRP51I32V | L10I, I15V, K20R, L24I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, L89M |
29 ± 8 (9) | ND | ND | ND |
rHIVDRVRP51F33L | L10I, I15V, K20R, L24I, V32I, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, L89M |
120 ± 33 (38) | ND | ND | ND |
rHIVDRVRP51M54I | L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, L63P, K70Q, V82I, I84V, L89M |
43 ± 15 (14) | ND | ND | ND |
rHIVDRVRP51V84I | L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, L89M |
28 ± 6 (9) | ND | ND | ND |
rHIVDRVRP51 | L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, L89M |
330 ± 10 (106) | ND | ND | ND |
rHIVV32I/L33F/I54M/I84V | V32I, L33F, I54M, I84V | 639 ± 17 (205) | ND | ND | ND |
rHIVV32I | V32I | 0.2 ± 0.05 (0.06) | 31 ± 3 (1.3) | 32 ± 6 (1.1) | 4.7 ± 0.5 (1.0) |
rHIVL33F | L33F | 3.2 ± 0.1 (1.0) | 35 ± 2 (1.3) | 45 ± 12 (1.5) | 5.6 ± 1.1 (1.1) |
rHIVI54M | I54M | 2.7 ± 0.1 (0.9) | 324 ± 86 (13) | 34 ± 17 (1.1) | 5.1 ± 2.2 (1.0) |
rHIVI84V | I84V | 3.3 ± 0.3 (1.1) | 313 ± 98 (13) | 44 ± 18 (1.5) | 6.4 ± 6.0 (1.3) |
Data shown represent mean IC50 values (±1 standard deviation) derived from the results of three independent experiments conducted in triplicate. The IC50s were determined by employing MT-4 cells exposed to each infectious HIV-1 clone (50 TCID50s) in the presence of each inhibitor and using the inhibition of p24 Gag protein production as an end point. The fold change values in parentheses were calculated by dividing IC50s against each virus by the IC50 against rHIVWT. ND, not determined.
APV, amprenavir, a protease inhibitor.
AZT, zidovudine, a nucleoside reverse transcriptase inhibitor.
RAL, raltegravir, an integrase strand transfer inhibitor.