TABLE 5.
Antiviral activity of darunavir and GRL-1388 against GRL-1398-resistant HIV-1a
| Virus | Amino acid substitutions in protease | Mean EC50 (nM) ± SD |
||
|---|---|---|---|---|
| DRV | GRL-1388 | GRL-1398 | ||
| HIV-1NL4-3 | 3.1 ± 0.4 | 3.0 ± 0.3 | 0.2 ± 0.1 | |
| HIV-1GRL1398-1μMExp.I | L10F, M46I, I47V, I50V, A71V, I84V | 67.3 ± 12.0 | 151.9 ± 10.5 | 505.1 ± 168.0 |
| HIV-1GRL1398-1μMExp.II | L10F, A28S, L33F, M46I | >1,000 | >1,000 | 552.8 ± 213.3 |
a
GRL-1398-resistant HIV-1 was selected in vitro by propagating HIV-1NL4-3 in the presence of increasing concentrations of GRL-1398 in MT-4 cells (Fig. 4). All assays to determine the EC50s were conducted in duplicate or triplicate, and the data shown represent mean values (±1 standard deviation) derived from the results of three independent assays.