TABLE 1.
V36 substitutions observed in patients included in the PROVE2 clinical trial
| V36 variant | No. (%) of V36 variants in PROVE 2 trial |
NS3/4A protease enzyme assaya |
HCV replicon assaya |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Variant found as dominant (100%) viral population at baseline (n = 241) | Variant found as dominant (100%) viral population at the time of breakthrough or relapse (n = 64) | Mean IC50 (μM) ± SD | Mean fold change in IC50 relative to wild type ± SD | Mean Km (μM) ± SD | Mean Vmax (μM/μg/s) ± SD | Mean EC50 (μM) ± SDc | Mean fold change in EC50 relative to wild type ± SD | Mean relative replication capacity ± SDd | |
| V36 (wild type) | 227 (94) | 40 (62.5) | 0.6 ± 0.2 | 1.0 ± 0.5 | 10.1 ± 6.1 | 0.0026 ± 0.0007 | 0.4 ± 0.1 | 1.0 | 100 |
| V36M | 2 (0.8) | 18 (28.1) | 3.0 ± 0.8 | 5.0 ± 1.8 | 5.1 ± 1.3 | 0.0018 ± 0.0002 | 3.4 ± 0.8b | 7.0 ± 1.6b | 77 ± 12b |
| V36A | 0 (0) | 4 (6.3) | NAe | NA | NA | NA | 3.6 ± 1.1b | 7.4 ± 2.2b | 104 ± 26b |
| V36L | 10 (4.1) | 6 (9.4) | 1.3 ± 0.1 | 2.2 ± 0.6 | 4.6 ± 1.0 | 0.0022 ± 0.0002 | 1.1 ± 0.2b | 2.2 ± 0.4b | NTf |
| V36C | 0 (0) | 1 (1.6) | 2.4 ± 1.3 | 4.0 ± 1.3 | 6.4 ± 2.6 | 0.0023 ± 0.0004 | 3.8 ± 0.5 | 9.5 ± 0.9 | 98 ± 9 |
a
Results were calculated based on three independent experiments.
b
Data from Zhou et al. (6); fold change calculated with respect to their wild-type sequence.
c
Data generated with a stable replicon.
d
Data generated with a transient replicon.
e
NA, no soluble protein obtained.
f
NT, not tested.