Sofosbuvir
| 1. Harvoni US Product Lable | ||||||||
|---|---|---|---|---|---|---|---|---|
| 2. Chariton (2016) EASL PS099 | ||||||||
| 3. EASL Guidelines 2106 | ||||||||
| 4. Xu et al. (2017) Antiviral therapy 22:587-97. | ||||||||
| 5. Verrmhren et al. Www.natap.org/2017/AASLD_156.htm | ||||||||
| 6. Camus G, J Viral Hepat. 2017;00:1–10. https://doi.org/10.1111/jvh.12795 | ||||||||
| Sofosbuvir in GT4 | ||||||||
| EC50 (uM) | Fold-shift | Phenotype | Repliation Fitness | Clinical RAS | Reference | Comments | ||
| WT | 0.014-0.11 | 1x | likely susceptible | 100 (6) | 1,6 | |||
| K231A | 1.3x | likely susceptible | 101 | 4 | ||||
| E237G | 1.3x | resistance possible | 66 | Yes | 2,4 | clinical TE RAV (2) | ||
| S282T | 6.x | resistance likely | 5.3 | Yes | 1,3,4,6 | clinical TE RAV (5) | ||
| S282T+V321I | 3x | resistance likely | 2.7 | 6 | ||||
| S282R | resistance likely | catalytic triad | ||||||
| S282G | resistance likely | catalytic triad | ||||||
| V321I | 0.7x | resistance possible | 23.6 | Yes | 6,1 | clinical RAV n=2 | ||
| A324V | 0.9x | likely susceptible | 46 | 4 | ||||
| The current dataset does not contain resistance possible classification | ||||||||
| >2.5x FS, resistance likely | ||||||||
| All S282 substitutions are considered resistance likely | ||||||||
| Multiple RASs: | ||||||||
| Data for variants with multiple mutations take precedence over estimation from individual RASs | ||||||||
| If RAV data are not available, follow rules for individual RASs in the variant | ||||||||
| 2 likely susceptible = likely susceptible | ||||||||
| 2 resistance possible = resistance likely | ||||||||
| likely susceptible + resistance possible = resistance possible | ||||||||
| >/= 1 resistance likely RASs = resistance likely | ||||||||
| Clinical RAV: | ||||||||
| without data but observed in Clinical VF = resistance possible | ||||||||
| likely susceptible RASs + clinical RAV = resistance possible | ||||||||
| Positions monitored for "Mutations Detected, effects unknown" | ||||||||
| 159, 282, 316, 320, 321 | ||||||||
| For NGS data: only RASs with >/=2% frequency will be included | ||||||||
| strikthrough= mutations obsreved in VFs with NGS but deemed unimportant by FDA. | ||||||||
| 1. Harvoni US Product Lable |
| 2. Chariton (2016) EASL PS099 |
| 3. EASL Guidelines 2106 |
| 4. Xu et al. (2017) Antiviral therapy 22:587-97. |
| 5. Verrmhren et al. Www.natap.org/2017/AASLD_156.htm |
| 6. Camus G, J Viral Hepat. 2017;00:1–10. https://doi.org/10.1111/jvh.12795 |