TABLE 3.
Activity of UIC-94017 against laboratory PI-resistant HIV-1a
| Virus | Amino acid substitutions in the protease | IC50 (μM)
|
|||||
|---|---|---|---|---|---|---|---|
| SQV | APV | IDV | NFV | RTV | UIC-94017 | ||
| HIV-1NL4-3 | Wild type | 0.009 ± 0.002 | 0.027 ± 0.008 | 0.011 ± 0.002 | 0.020 ± 0.005 | 0.018 ± 0.004 | 0.003 ± 0.0005 |
| HIV-1SQV5μM | L101, G48V, I54V, L90M | >1 (>111) | 0.17 ± 0.09 (6) | >1 (>91) | 0.30 ± 0.04 (15) | >1 (>56) | 0.005 ± 0.0009 (2) |
| HIV-1APV5μM | L10F, V32I, M46I, I54M, A71V, I84V | 0.02 ± 0.008 (2) | >1 (>37) | 0.31 ± 0.05 (28) | 0.21 ± 0.05 (11) | >1 (>56) | 0.22 ± 0.05 (73) |
| HIV-1IDV5μM | L10F, L24I, M46I, L63P, A71V, G73S, V82T | 0.015 ± 0.004 (2) | 0.33 ± 0.01 (12) | >1 (>91) | 0.74 ± 0.04 (37) | >1 (>56) | 0.029 ± 0.0007 (10) |
| HIV-1NFV5μM | L10F, D30N, K45I, A71V, T74S | 0.031 ± 0.009 (3) | 0.093 ± 0.003 (3) | 0.28 ± 0.08 (25) | >1 (>50) | 0.09 ± 0.06 (5) | 0.003 ± 0.0002 (1) |
| HIV-1RTV5μM | M46I, V82F, I84V | 0.013 ± 0.009 (1) | 0.61 ± 0.29 (23) | 0.31 ± 0.07 (28) | 0.24 ± 0.09 (12) | >1 (>56) | 0.025 ± 0.006 (8) |
a
MT-4 cells (104) were exposed to each HIV-1 (100 TCID50s), and the inhibition of p24 Gag protein production by the drug was used as an endpoint. The numbers in parentheses represent the fold changes of IC50s for each isolate compared to the IC50s for HIV-1NL4-3. The data shown are means ± 1 standard deviation derived from the results of three independent experiments conducted in triplicate.