Table 3.
Antiviral activity against resistant HIV-1 variants.
| Virus speciesa | Antiviral EC50 (μM) (fold change) | ||||
|---|---|---|---|---|---|
| DRV | U7 | PU7 | U9 | PU9 | |
| HIV-1-WT | 0.008 ± 0.002 | 0.003 ± 0.001 | 0.005 ± 0.001 | 0.006 ± 0.001 | 0.003 ± 0.002 |
| HIV-1-SLK | 0.056 ± 0.01 (7) | NT | <0.010 (<2) | NT | <0.010 (<3) |
| HIV-1-Gag-PR | 0.77 ± 0.13 (96) | 0.14 ± 0.02 (47) | 0.038 ± 0.005 (6) | NT | NT |
| HIV-1-RT-PR | 1.46 ± 0.13 (183) | 0.25 ± 0.03 (83) | 0.085 ± 0.006 (17) | NT | NT |
| HIV-1-V3 (virus culture) | 1.06 ± 0.52 (133) | 0.80 ± 0.18 (267) | 5.33 ± 1.34 (1066) | 11.1 ± 13.2 (1850) | 1.17 ± 2.03 (390) |
| HIV-1-V4 (virus culture) | 15.8 ± 4.3 (1975) | 5.38 ± 1.38 (1793) | 1.06 ± 0.41 (212) | 5.77 ± 1.44 (962) | 3.90 ± 1.50 (1300) |
| HIV-1-V5 (virus culture) | 1.87 ± 2.22 (234) | 21.8 ± 11.1 (7267) | 0.37 ± 0.11 (74) | 6.44 ± 4.69 (1073) | 13.4 ± 11.0 (4467) |
| HIV-1-V9 (virus culture) | 12.9 ± 9.5 (1613) | 16.7 ± 2.0 (5567) | 0.54 ± 0.18 (108) | >100 (>16667) | 2.85 ± 0.71 (950) |
| HIV-1-DRV (virus culture) | >100 (>12500) | 1.60 ± 0.49 (533) | 0.28 ± 0.12 (56) | 0.78 ± 0.19 (130) | 0.22 ± 0.11 (73) |
NT: not tested.
The resistant HIV-1 variants contain the following amino acid substitutions in HIV-1 protease compared to the wild-type NL4-3 strain.
HIV-1-SLK: L10I, V11I, I13V, K14R, A22V, E35D, M36I, N37D, G48M, F53L, I54V, I62V, L63P, A71V, T74S, V82A, I84V, T91S, Q92K
HIV-1-Gag-PR/RT-PR: I13V, G16E, V32I, L33F, K45I, M46I, A71V, L76V, V82F, I84V (additional mutations in the Gag and RT regions)
HIV-1-V3: L10F, L33F, M46I, I47V, I50V, F53L, L63P, A71V, L76S, V82I, I85V, L89I (81%)
HIV-1-V4: L10F, V11I, I13V, V32I, L33F, K43T, M46L, I54L, A71V, V82I, I84V, L89M, T91S, Q92R (93%)
HIV-1-V5: L10F, I15V, M46I, I47V, I50V, F53L, A71V, V82I, I84V, L89T (89%)
HIV-1-V9: L10F, I13V, L33F, K45R, M46I, I47V, I50V, F53L, I54L, I66F, A71V, T74A, L76S, V82I (95%)