TABLE 2.
Antiviral effects against selected PI-resistant HIV-1 variants and recombinant clinical HIV-1 isolates
| HIV straina | Mean EC50
b
|
|||
|---|---|---|---|---|
| DRV | GRL-003-15 | GRL-001-15 | GRL-121-13 | |
| HIVNL4-3 | 3.0 ± 0.3 | 0.049 ± 0.02 | 0.061 ± 0.008 | 0.30 ± 0.02 |
| HIVSQV-5μM | 29 ± 17 (10) | 0.0032 ± 0.0002 (0.06) | 0.37 ± 0.05 (6) | 0.015 ± 0.02 (0.05) |
| HIVAPV-5μM | 98 ± 83 (33) | 0.0021 ± 0.0001 (0.04) | 0.00068 ± 0.00009 (0.01) | 0.068 ± 0.09 (0.2) |
| HIVLPV-5μM | 346 ± 93 (115) | 0.00015 ± 0.00001 (0.003) | 0.0040 ± 0.0005 (0.07) | 0.0022 ± 0.0006 (0.007) |
| HIVIDV-5μM | 22 ± 2 (7) | 0.00037 ± 0.00002 (0.007) | 0.00020 ± 0.00003 (0.003) | 0.0056 ± 0.005 (0.02) |
| HIVNFV-5μM | 5.1 ± 3.7 (2) | 0.00089 ± 0.0001 (0.02) | 0.00019 ± 0.0001 (0.03) | 0.024 ± 0.03 (0.08) |
| HIVATV-5μM | 24 ± 1 (8) | 0.00084 ± 0.0001 (0.02) | 0.0020 ± 0.001 (0.03) | 0.046 ± 0.07 (0.2) |
| HIVTPV-15μM | 29 ± 16 (10) | 0.0005 ± 0.00004 (0.01) | 0.057 ± 0.007 (0.9) | 0.087 ± 0.03 (0.3) |
| HIVDRVRP20 | 81 ± 4 (27) | 2.2 ± 0.1 (45) | 0.37 ± 0.04 (6) | 4.3 ± 1 (14) |
| HIVDRVRP30 | 216 ± 9 (72) | 3.3 ± 0.2 (66) | 0.17 ± 0.02 (3) | 23 ± 0.4 (77) |
| HIVDRVRP51 | 2707 ± 13 (902) | 38 ± 3 (771) | 36 ± 4 (594) | 99 ± 13 (330) |
| rCLHIVF16 | 2498 ± 122 (833) | 0.00063 ± 0.00004 (0.01) | 0.00044 ± 0.00005 (0.01) | 2.0 ± 0.7 (7) |
| rCLHIVF39 | 322 ± 13 (107) | 3.6 ± 0.2 (73) | 3.6 ± 0.5 (60) | 4.3 ± 0.7 (14) |
| rCLHIVV42 | 371 ± 39 (124) | 3.9 ± 0.3 (79) | 4.3 ± 0.6 (71) | 16 ± 6 (53) |
| rCLHIVT45 | 190 ± 20 (63) | 3.6 ± 0.2 (73) | 3.6 ± 0.5 (60) | 3.3 ± 0.2 (11) |
| rCLHIVT48 | 324 ± 12 (108) | 0.034 ± 0.002 (0.7) | 0.37 ± 0.05 (6) | 0.61 ± 0.5 (2) |
| rCLHIVF71 | 332 ± 45 (111) | 3.9 ± 0.3 (79) | 4.1 ± 0.5 (67) | 17 ± 8 (57) |
The amino acid substitutions identified in the proteases of laboratory-selected FDA-approved HIV variants (HIVSQV-5μM, HIVAPV-5μM, HIVLPV-5μM, HIVIDV-5μM, HIVNFV-5μM, HIVATV-5μM, and HIVTPV-15μM and the HIVDRVRs HIVDRVRP20, HIVDRVRP30, and HIVDRVRP51) and recombinant clinical HIV isolates (rCLHIVF16, rCLHIVF39, rCLHIVV42, rCLHIVT45, rCLHIVT48, and rCLHIVF71) compared to the wild-type HIVNL4-3 are illustrated in Fig. S1 in the supplemental material.
Numbers in parentheses represent the fold change in the EC50 for each isolate compared to the EC50 for wild-type HIVNL4-3. All assays were conducted in duplicate, and the data shown represent mean values (± 1 standard deviation) derived from the results of three independent experiments.