Table 1. NNRTI susceptibility of WT and mutant HIV-1 RT.
The concentrations of NNRTI required to inhibit the activity of purified RT and TyHRT by 50% (IC50) are reported as an average of three independent experiments±S.D. The effective concentrations of NNRTI required to inhibit virus replication by 50% (EC50) are reported as an average of two independent experiments±S.D. Values in parentheses indicate fold-resistance.
| IC50/EC50 | ||||
|---|---|---|---|---|
| RT | Assay | Efavirenz (nM) | Nevirapine (μM) | Delavirdine (μM) |
| WT | Purified RT | 94.16±6.33 (1.0) | 7.22±1.38 (1.0) | 2.18±0.62 (1.0) |
| TyHRT | 1.73±0.64 (1.0) | 1.16±0.55 (1.0) | * | |
| Antiviral | 0.90±0.00 (1.0) | 0.03±0.00 (1.0) | 0.04±0.01 (1.0) | |
| I132A | Purified RT | 90.07±5.11 (1.0) | 18.05±2.35 (2.5) | 8.70±1.02 (4.0) |
| TyHRT | 2.78±0.97 (1.6) | 1.95±0.52 (1.7) | * | |
| I132M | Purified RT | 432.42±11.31 (4.6) | 62.09±3.69 (8.6) | 30.25±3.35 (13.9) |
| TyHRT | 6.63±2.43 (3.7) | 7.10±1.67 (6.1) | * | |
| Antiviral | 2.00±0.00 (2.2) | 1.25±1.10 (42) | 0.80±0.20 (20.0) | |
| I135A | Purified RT | 188.08±9.34 (2.0) | 87.36±4.56 (12.1) | 34.60±5.59 (15.9) |
| TyHRT | 1.62±0.47 (0.9) | 1.63±0.58 (1.4) | * | |
| I135M | Purified RT | 197.09±13.18 (2.1) | 38.99±2.89 (5.4) | 3.92±0.99 (1.8) |
| TyHRT | 2.76±1.15 (1.6) | 2.02±0.50 (1.7) | * | |
| Antiviral | 2.00±0.00 (2.2) | 0.07±0.01 (2.3) | 0.05±0.02 (1.3) | |
| N136A† | ||||
| N137A | Purified RT | 87.35±22.28 (0.9) | 6.50±1.10 (0.9) | 1.52±0.55 (0.7) |
| TyHRT | 1.30±0.14 (0.8) | 1.28±0.37 (1.1) | * | |
| E138A | Purified RT | 188.08±12.11 (2.0) | 13.72±1.57 (1.9) | 7.62±0.91 (3.5) |
| TyHRT | 4.11±2.09 (2.4) | 1.19±1.03 (1.0) | * | |
| E138K | Purified RT | 216.34±12.13 (2.3) | 15.88±2.26 (2.2) | 13.06±1.56 (6.0) |
| TyHRT | 3.52±1.04 (2.0) | 1.51±0.75 (1.3) | * | |
| T139A† | ||||
| T139V | Purified RT | 113.44±9.23 (1.2) | 12.27±1.89 (1.7) | 2.61±0.97 (1.2) |
| TyHRT | 1.74±0.85 (1.0) | 1.85±0.24 (1.6) | * | |
| P140A† | ||||
*Delavirdine is not soluble in yeast media.
†RT activity too low to effectively evaluate NNRTI susceptibility.