TABLE 3.
Effects of L33I, L33F, I54V, and V82T substitutions on the susceptibility of cHIVNL4-3 and cHIVB to TPVa
| Infectious clone | Amino acid substitution(s) in PR | Mean ± SD IC50 (μM) | Fold resistance |
|---|---|---|---|
| cHIVNL4-3 | Wild type | 0.27 ± 0.003 | 1 |
| cHIVNL4-3L33I | L33I | Does not replicate | |
| cHIVNL4-3L33F | L33F | 0.27 ± 0.001 | 1 |
| cHIVNL4-3I54V | I54V | 0.37 ± 0.005 | 1 |
| cHIVNL4-3V82T | V82T | 0.31 ± 0.025 | 1 |
| cHIVNL4-3V82L | V82L | 0.33 ± 0.023 | 1 |
| cHIVNL4-3L33I/M36I | L33I, M36I | 0.33 ± 0.004 | 1 |
| cHIVNL4-3I54V/V82T | I54V, V82T | 0.28 ± 0.004 | 1 |
| cHIVB | L10I, L33I, M36I, M46I, F53L, K55R, I62V, L63P, A71V, G73S, V82A, L90M, I93L | 0.30 ± 0.02 | 1 |
| cHIVBI33L | L10I, M36I, M46I, F53L, K55R, I62V, L63P, A71V, G73S, V82A, L90M, I93L | 0.26 ± 0.03 | 1 |
| cHIVBI54V | L10I, L33I, M36I, M46I, I54V, K55R, I62V, L63P, A71V, G73S, V82A, L90M, I93L | 2.9 ± 0.11 | 11 |
| cHIVBI54V/V82T | L10I, L33I, M36I, M46I, I54V, K55R, I62V, L63P, A71V, G73S, V82T, L90M, I93L | 3.2 ± 0.1 | 12 |
| cHIVBI33L/154V | L10I, M36I, M46I, I54V, K55R, I62V, L63P, A71V, G73S, V82A, L90M, I93L | 1.2 ± 0.19 | 4 |
| cHIVBI33L/154V/V82T | L10I, M36I, M46I, I54V, K55R, I62V, L63P, A71V, G73S, V82T, L90M, I93L | 2.5 ± 0.26 | 9 |
a
Data shown represent mean 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 PI and using the inhibition of p24 Gag protein production as the endpoint.