TABLE 2.
Antiviral activities of GRL-015, -085, and -097 against in vitro PI-selected HIV-1 variantsa
| Viral variant | Mean EC50 (nM) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GRL-015 | GRL-085 | GRL-097 | GRL-012 | APV | LPV | ATV | DRV | AZT | 3TC | TDF | DTG | |
| HIV-1NL4-3 | 3.3 ± 0.4 | 3.2 ± 0.3 | 46 ± 21 | 3.2 ± 0.6 | 25 ± 2 | 12 ± 1 | 2.6 ± 0.6 | 2.8 ± 0.4 | 21 ± 7 | 420 ± 230 | 490 ± 190 | 0.4 ± 0.1 |
| HIV-1APV-5μM | 2.6 ± 0.8 (0.8) | 1.9 ± 0.2 (0.6) | 18 ± 4 (0.4) | 17 ± 3.2 (5.3) | >1,000 (>41) | 230 ± 18 (19) | 2.4 ± 0.7 (0.9) | 198 ± 21 (70) | ND | ND | ND | ND |
| HIV-1LPV-5μM | 2.5 ± 0.5 (0.7) | 2.6 ± 0.4 (0.8) | 32 ± 3 (0.7) | 2.1 ± 1.1 (0.6) | 340 ± 40 (14) | >1,000 (>83) | 36 ± 9 (14) | 28 ± 6 (10) | ND | ND | ND | ND |
| HIV-1ATV-5μM | 2.3 ± 0.4 (0.7) | 2.4 ± 0.6 (0.8) | 29 ± 4 (0.6) | 1.2 ± 0.7 (0.4) | 480 ± 10 (20) | 360 ± 50 (30) | >1,000 (>385) | 4.8 ± 0.4 (1.7) | ND | ND | ND | ND |
| HIV-1SQV-5μΜ | 2.8 ± 0.1 (0.8) | 2.7 ± 0.5 (0.8) | 30 ± 3 (0.7) | 3.0 ± 0.1 (0.9) | 365 ± 22 (15) | >1,000 (>83) | 430 ± 20 (165) | 15 ± 10 (5.3) | ND | ND | ND | ND |
| HIV-1TPV-15μM | 3.4 ± 0.4 (1.0) | 3.9 ± 0.7 (1.2) | 210 ± 20 (5) | 34 ± 6 (11) | >1,000 (>41) | >1,000 (>83) | >1,000 (>385) | 33 ± 1 (12) | ND | ND | ND | ND |
| HIV-1DRVRP30 | 16 ± 3 (4.7) | 2.8 ± 0.2 (0.9) | 28 ± 3 (0.6) | 1.2 ± 0.1 (0.4) | >1,000 (>41) | >1,000 (>83) | >1,000 (>385) | 222 ± 31 (80) | >1,000 (>48) | >1,000 (>2.4) | >1,000 (>2) | 0.3 ± 0.1 (0.8) |
| HIV-1DRVRP40 | 230 ± 40 (69) | 29 ± 6 (9) | 280 ± 40 (6) | 66 ± 23 (30) | >1,000 (>41) | >1,000 (>83) | >1,000 (>385) | 2,500 ± 500 (910) | ND | ND | ND | ND |
| HIV-1DRVRP51 | 220 ± 20 (68) | 42 ± 1 (13) | 310 ± 60 (6.8) | 170 ± 30 (53) | >1,000 (>41) | >1,000 (>83) | >1,000 (>385) | 2,800 ± 300 (1022) | >1,000 (>48) | >1,000 (>2.4) | >1,000 (>2) | 0.3 ± 0.5 (0.8) |
The amino acid substitutions identified in protease of HIV-1APV-5μM, HIV-1LPV-5μM, HIV-1ATV-5μM, HIV-1SQV-5μM, HIV-1TPV-15μM, HIV-1DRVRP30, HIV-1DRVRP40, and HIV-1DRVRP51 compared to the wild-type HIV-1NL4-3 include L10F/V32I/L33F/M46L/I54M/A71V, L10F/V32I/M46I/I47A/A71V/I84V, L23I/E34Q/K43I/M46I/I50L/G51A/L63P/A71V/V82A/T91A, L10I/N37D/G48V/I54V/L63P/G73C/I84V/L90M, L10I/L33I/M36I/M46I/I54V/K55R/I62V/L63P/A71V/G73S/V82T/L90M/I93L, L10I/I15V/K20R/L24I/V32I/M36I/M46L/L63P/K70Q/V82A/I84V/L89M, L10I/I15V/K20R/L24I/V32I/L33F/M36I/R41K/M46L/I54M/L63P/K70Q/V82A/I84V/L89M, and L10I/I15V/K20R/L24I/V32I/L33F/M36I/M46L/I54M/L63P/K70Q/V82I/I84V/L89M, respectively. Numbers in parentheses are fold changes in EC50 for each isolate compared to the EC50 for wild-type HIV-1NL4-3. All assays were conducted in triplicate, and the data are means ± 1 standard deviation derived from the results of three independent experiments. ND, not determined.