Table 1.
Effect of N348I on Etravirine and Tenofovir Resistance
| Strain | Amino acid at Indicated RT Codona | Etravirine | Tenofovir | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 41 | 103 | 181 | 210 | 215 | 348 | Mean EC50 ± SE (μM)b | Resistance (fold)c | Mean EC50 ± SE(μM)d | Resistance (fold)c | |
| NL | M | K | Y | L | T | N | 0.0056 ± 0.0003 | 1 | 6.1 ± 0.6 | 1 |
| NL/348 | - | - | - | - | - | I | 0.0090 ± 0.0014 | 1.6 | 4.0 ± 0.9 | 0.7 |
| NL/103 | - | N | - | - | - | - | 0.0084 ± 0.0025 | 1.5 | ND | - |
| NL/103+348 | - | N | - | - | - | I | 0.0086 ± 0.0014 | 1.5 | ND | - |
| NL/181 | - | - | C | - | - | - | 0.0125 ± 0.0024 | 2.2 | ND | - |
| NL/181+348 | - | - | C | - | - | I | 0.0360 ± 0.0084 | 6.4 | ND | - |
| NL/2AZT | L | - | - | - | Y | - | ND | - | 7.5 ± 0.8 | 1.2 |
| NL/2AZT+348 | L | - | - | - | Y | I | ND | - | 10.6 ± 0.6 | 1.7 |
| HX | - | - | - | - | - | - | ND | - | 3.0 ± 0.3 | 1 |
| HX/348 | - | - | - | - | - | I | ND | - | 4.1 ± 0.9 | 1.4 |
| HX/3AZT | L | - | - | W | Y | - | ND | - | 5.8 ± 1.2 | 1.9 |
| HX/3AZT+348 | L | - | - | W | Y | I | ND | - | 18.0 ± 4.1 | 6.0 |
RT amino acid residues shown are numbered as for NL4.3 (NL) and HXB-2 (HX) and are those that differ from WT sequences.
Effective concentration (EC50) and standard error (SE) values were determined in drug susceptibility assays performed in the TZM-bl indicator cell line from at least four independent assays. The differences between the etravirine EC50 values for NL compared to NL/348 (p=0.019, n=4), NL/103+348 (p=0.019, n=5), NL/181 (p=0.02, n=4) and NL/181+348 (p=0.02, n=4) were statistically significant as was NL/181+348 compared to NL/181 (p=0.03, n=4). The difference in the etravirine EC50 values for NL/103 (p=0.54, n=5) compared to NL was not statistically significant. Statistical analyses were performed using the Wilcoxon Rank Sum test. ND denotes not done.
The differences between the etravirine or tenofovir EC50 values for mutant strain divided by the EC50 for corresponding WT strain. Values >1 indicate resistance. Statistically significant differences compared to WT are denoted in bold-type.
The differences between the tenofovir EC50 for NL and NL2AZT+348 (p=0.014, n=4), and HX compared to HX/3AZT (p=0.05, n=4) and HX/3AZT+348 (p=0.009, n=5) were statistically significant as was HX/3AZT+348 compared to HX/3AZT (p=0.008, n=4). The difference in the tenofovir EC50 values for NL/2AZT and HX/348 compared to the corresponding WT strain was not statistically significant. ND denotes not done.