TABLE 2.
Antiviral activities of GRL-1388 and -1398 against laboratory PI-selected HIV-1variantsa
| Virus | Mean EC50 in nM ± SD (fold change) |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| SQV | RTV | NFV | LPV | ATV | APV | DRV | GRL-1388 | GRL-1398 | |
| HIV-1NL4-3 | 5.2 ± 1.7 | 40.4 ± 4.9 | 30.2 ± 3.0 | 27.8 ± 5.3 | 2.5 ± 0.8 | 34.3 ± 1.3 | 3.2 ± 0.3 | 3.1 ± 0.2 | 0.2 ± 0.1 |
| HIV-1SQV-5μM | >1,000 (192) | >1,000 (>25) | >1,000 (>33) | >1,000 (>36) | 415.0 ± 15.1 (166) | 353.7 ± 12.4 (10) | 30.4 ± 0.5 (10) | 32.6 ± 7.5 (11) | 5.7 ± 1.3 (29) |
| HIV-1RTV-5μM | 66.3 ± 8.9 (13) | >1,000 (>25) | 386.4 ± 84.7 (13) | 698.3 ± 87.4 (25) | 32.5 ± 5.9 (13) | 334.5 ± 42.5 (10) | 19.9 ± 13.5 (6) | 28.8 ± 1.8 (9) | 3.1 ± 0.2 (16) |
| HIV-1NFV-5μM | 24.1 ± 6.3 (5) | 46.5 ± 9.4 (1) | >1,000 (>33) | 37.2 ± 3.3 (1) | 12.3 ± 2.2 (5) | 71.3 ± 10.5 (2) | 2.7 ± 0.4 (1) | 2.6 ± 0.4 (1) | 0.1 ± 0.1 (1) |
| HIV-1LPV-5μM | 33.5 ± 0.9 (6) | >1,000 (>25) | 401.6 ± 11.0 (13) | >1,000 (>36) | 17.0 ± 7.7 (7) | 320.7 ± 23.2 (9) | 4.0 ± 0.9 (1) | 29.9 ± 12.5 (10) | 3.5 ± 0.4 (18) |
| HIV-1ATV-5μM | 134.3 ± 22.8 (26) | >1,000 (>25) | >1,000 (>33) | >1,000 (>36) | >1,000 (>400) | 521.0 ± 124.1 (15) | 6.8 ± 0.6 (2) | 21.9 ± 7.7 (7) | 3.1 ± 0.4 (16) |
| HIV-1APV-5μM | 47.3 ± 2.1 (9) | >1,000 (>25) | >1,000 (>33) | 633.2 ± 21.0 (23) | 453.6 ± 12.2 (181) | >1,000 (>29) | 423.9 ± 6.0 (132) | 475.7 ± 38.1 (153) | 49.0 ± 1.1 (245) |
The amino acid substitutions identified in protease of HIV-1SQV-5μM, HIV-1RTV-5μM, HIV-1NFV-5μM, HIV-1LPV-5μM, HIV-1ATV-5μM, and HIV-1APV-5μM compared to the consensus type B sequence cited from the Los Alamos database include L10I/N37D/G48V/I54V/L63P/G73C/I84V/L90M, L10I/M46L/I54V/V82A, L10F/K20T/D30N/K45I/A71V/V77I, L10F/M46I/I54V/V82A, L23I/E34Q/K43I/M46I/I50L/G51A/L63P/A71V/V82A/T91A, and L10F/V32I/L33F/M46L/I54M/A71V, respectively. Numbers in parentheses represent fold changes in EC50s for each isolate compared to the EC50s for wild-type HIV-1NL4-3. All assays were conducted in duplicate or triplicate, and the data shown represent mean values (±1 standard deviation) derived from the results of three independent experiments.