Background
Results
Characterisation of the study group
Patient Group | Type of Response | Sex | Rx Naïve | Age (years) at Baseline | Viral Load log10 IU/ml at Baseline | Time points | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Pre treatment period | Early treatment period | Post treatment period | ||||||||||
Sustained virological response (SVR)
|
Mean Age 41 ± 12
|
Mean VL 5.66 ± 0.66
|
E
|
B
|
W1
|
W2
|
W3
|
W4
|
L
| |||
SVR3 | SVR | F | Yes | 28 | 5.47 | + | + | + | + | + | - (V) | TND |
SVR6 | SVR | F | Yes | 35 | 5.16 | + | + | - (V) | TND | TND | TND | TND |
SVR7 | SVR | F | Yes | 32 | 5.46 | + | + | + | - (V) | TND | TND | TND |
SVR8 | SVR | F | Yes | 59 | 6.89 | + | + | + | NA | NA | + (V) | TND |
SVR9 | SVR | F | No | 45 | 6.37 | + | + | + | + | NA | - (V) | TND |
SVR12 | SFR | F | Yes | 49 | 5.17 | + | + | TND | TND | TND | TND | TND |
Treatment failure (TF)
|
Mean Age 41 ± 7
|
Mean VL 6.23 ± 0.63
|
E
|
B
|
W1
|
W2
|
W4
|
W12*
|
L
| |||
NR2 | NR | F | Yes | 42 | 5.05 | + | + | + | NA | + | + | + (W3) |
R1 | R | M | Yes | 46 | 7.5 | + | + | + (V) | TND | TND | TND | + (W2) |
R4 | R | M | Yes | 45 | 7.11 | + | + | + | + (V) | TND | TND | + (W10) |
R13 | R | M | Yes | 31 | 6.32 | + | + | + | - | TND | TND | - (W12) |
Clonal analysis and sequences data
Genetic variation during the pre-treatment assessment period
Patient group | No. of patients | Time points | Interval mean weeks | Change in serum HCV RNA × 105 copy/ml | Change in Normalised Shannon Entropy (Nucleotides) | Change in Normalised Shannon Entropy (Amino Acids) | Change in genetic diversity (mean Hamming distance) | Change in genetic distance | |
---|---|---|---|---|---|---|---|---|---|
SVR
|
6
|
E vs B
| 34 ± 10 |
3.56 ± 9.01†
| 0.030 ± 0.297 | -0.026 ± 0.266 | -1.15 ± 4.56 | -0.005 ± 0.025 | |
4
|
B vs w1
| 1 ± 0 |
-17.21 ± 26.33†
| -0.177 ± 0.329 |
-0.111 ± 0.225*
| -0.05 ± 4.14 | 0.002 ± 0.026 | ||
2
|
B vs w2
| 2 ± 0 | -25.98 ± 30.95 | -0.001 ± 0.267 | -0.008 ± 0.257 | 1.10 ± 1.00 | -0.001 ± 0.004 | ||
2
|
B vs W3/4
| 3.5 ± 0.5 | -39.47 ± 38.11 | -0.243 ± 0.064 | -0.178 ± 0.156 | -3.35 ± 1.85 | -0.027 ± 0.015 | ||
HVR1
| |||||||||
TF
|
4
|
E vs B
| 24 ± 0 |
83.31 ± 92.20‡
| 0.147 ± 0.063 | 0.118 ± 0.141 | 8.75 ± 4.13 | 0.018 ± 0.032 | |
4
|
B vs w1
| 1 ± 0 |
-116.22 ± 125.37‡
| -0.126 ± 0.236 |
-0.086 ± 0.146*
| -7.63 ± 9.98 | -0.026 ± 0.036 | ||
2
|
B vs W2/4
| 3 ± 1 | -49.94 ± 56.35 | -0.073 ± 0.268 | -0.049 ± 0.220 | -0.50 ± 3.70 | -0.001 ± 0.016 | ||
3
|
B vs L
| 5 ± 4 | -33.70 ± 48.92 | -0.336 ± 0.348 | -0.398 ± 0.172 | -15.60 ± 15.99 | -0.054 ± 0.056 | ||
SVR
|
6
|
E vs B
| 0.092 ± 0.232 | 0.024 ± 0.174 | 0.02 ± 0.77 | 0.002 ± 0.006 | |||
4
|
B vs w1
| -0.104 ± 0.108 | -0.049 ± 0.142 | -0.45 ± 0.62 | -0.004 ± 0.005 | ||||
2
|
B vs w2
| 0.127 ± 0.047 | -0.003 ± 0.054 | 0.05 ± 0.05 | 0.000 ± 0.001 | ||||
2
|
B vs W3/4
| -0.071 ± 0.185 | -0.002 ± 0.026 | -1.35 ± 0.95 | -0.013 ± 0.010 | ||||
Outside
| |||||||||
TF
|
4
|
E vs B
| -0.089 ± 0.276 | -0.035 ± 0.223 | 0.18 ± 1.43 | -0.010 ± 0.018 | |||
4
|
B vs w1
| 0.064 ± 0.274 | 0.009 ± 0.065 | 0.15 ± 0.43 | -0.005 ± 0.008 | ||||
2
|
B vs W2/4
| 0.106 ± 0.239 | 0.032 ± 0.049 | 0.10 ± 0.10 | 0.001 ± 0.003 | ||||
3
|
B vs L
| -0.007 ± 0.109 | -0.049 ± 0.148 | 0.12 ± 0.48 | -0.007 ± 0.009 |
Genetic variation and molecular evolution of the HCV quasispecies during treatment in patients with different patterns of response
Phylogenetic analysis of the HCV quasispecies prior and during treatment in patient with different patterns of response
Intra-sample and inter-sample genetic distance variability during treatment in patient with different patterns of response
Region | Patient Group | Samples | aIntrasample variability | Samples | bIntersample variability | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Ks
|
Ka
|
Ka/Ks
| gd |
Ks
|
Ka
|
Ka/Ks
| gd | ||||
SVR
|
E
| 0.0195 ± 0.0141 | 0.0308 ± 0.0130 | 0.998 | 0.0283 ± 0.0095 | ||||||
B
| 0.0236 ± 0.0175 |
0.0225 ± 0.0115*
|
0.850
†
| 0.0233 ± 0.0091 |
B-B
| 0.0236 ± 0.0175 |
0.0225 ± 0.0115*
| 0.850 | 0.0233 ± 0.0091 | ||
W1
| 0.0277 ± 0.0152 | 0.0302 ± 0.0100 |
1.067
‡
| 0.0302 ± 0.0087 |
B-W1
| 0.0293 ± 0.0160 | 0.0305 ± 0.0110 | 1.041 | 0.0305 ± 0.0095 | ||
W2
| 0.0050 ± 0.0025 | 0.0375 ± 0.0155 | 2.700 | 0.0280 ± 0.0125 |
B-W2
| 0.0070 ± 0.0045 | 0.0370 ± 0.0205 | 7.300 | 0.0285 ± 0.0125 | ||
W3/W4
| 0.0000 ± 0.0000 | 0.0135 ± 0.0075 | NA | 0.0095 ± 0.0045 |
B-W3/4
| 0.0015 ± 0.0015 | 0.0150 ± 0.0085 | 9.333 | 0.0110 ± 0.0055 | ||
HVR1
| |||||||||||
NR
|
E
| 0.0292 ± 0.0185 | 0.0585 ± 0.0207 | 1.860 | 0.0492 ± 0.0145 | ||||||
B
| 0.0345 ± 0.0192 |
0.0802 ± 0.0227*
|
2.427
†
| 0.0667 ± 0.0185 |
B-B
| 0.0345 ± 0.0192 |
0.0802 ± 0.0227*
| 2.427 | 0.0667 ± 0.0185 | ||
W1
| 0.0172 ± 0.0115 | 0.0507 ± 0.0175 |
2.033
‡
| 0.0412 ± 0.0135 |
B-W1
| 0.0218 ± 0.0125 | 0.0538 ± 0.0178 | 2.332 | 0.0432 ± 0.0130 | ||
W2/4
| 0.0205 ± 0.0175 | 0.0320 ± 0.0135 | 1.574 | 0.0290 ± 0.0115 |
B-W2/4
| 0.0200 ± 0.0100 | 0.0325 ± 0.0135 | 1.648 | 0.0295 ± 0.0120 | ||
L
| 0.0160 ± 0.0033 | 0.008 ± 0.0036 | 0.285 | 0.0106 ± 0.0043 |
B-L
| 0.0153 ± 0.008 | 0.0133 ± 0.0057 | 0.873 | 0.0137 ± 0.0047 | ||
Outside
| |||||||||||
SVR
|
E
| 0.0106 ± 0.005 | 0.0023 ± 0.0015 | 0.216 | 0.0045 ± 0.0016 | ||||||
B
| 0.0130 ± 0.0061 | 0.0036 ± 0.0020 | 0.277 | 0.0061 ± 0.0023 |
B-B
| 0.0130 ± 0.0061 | 0.0036 ± 0.0020 | 0.277 | 0.0061 ± 0.0023 | ||
W1
| 0.0052 ± 0.0022 | 0.0017 ± 0.0015 | 0.327 | 0.0027 ± 0.0012 |
B-W1
| 0.0050 ± 0.0020 | 0.0018 ± 0.0018 | 0.360 | 0.0025 ± 0.0013 | ||
W2
| 0.0035 ± 0.0025 | 0.0025 ± 0.0015 | 0.714 | 0.0025 ± 0.0020 |
B-W2
| 0.0035 ± 0.0025 | 0.0025 ± 0.0020 | 0.714 | 0.0025 ± 0.0020 | ||
W3/W4
| 0.0015 ± 0.0015 | 0.0010 ± 0.0010 | 0.667 | 0.0010 ± 0.0010 |
B-W3/4
| 0.0015 ± 0.0015 | 0.0010 ± 0.0010 | 0.667 | 0.0010 ± 0.0010 | ||
NR
|
E
| 0.0612 ± 0.0205 | 0.0042 ± 0.0025 | 0.068 | 0.0180 ± 0.0052 | ||||||
B
| 0.0280 ± 0.0115 | 0.0017 ± 0.0012 | 0.061 | 0.0085 ± 0.0032 |
B-B
| 0.0280 ± 0.0115 | 0.0017 ± 0.0012 | 0.061 | 0.0085 ± 0.0032 | ||
W1
| 0.0132 ± 0.0085 | 0.0005 ± 0.0005 | 0.038 | 0.0040 ± 0.0022 |
B-W1
| 0.0148 ± 0.0090 | 0.0008 ± 0.0008 | 0.054 | 0.0043 ± 0.0025 | ||
W2/4
| 0.0100 ± 0.0060 | 0.0015 ± 0.0010 | 0.150 | 0.0047 ± 0.0026 |
B-W2/4
| 0.0095 ± 0.0060 | 0.0015 ± 0.0010 | 0.158 | 0.0035 ± 0.0020 | ||
L
| 0.0133 ± 0.0060 | 0.0006 ± 0.0006 | 0.045 | 0.0030 ± 0.0020 |
B-L
| 0.0140 ± 0.0057 | 0.0010 ± 0.0010 | 0.071 | 0.0043 ± 0.0020 |