Table 2.
Deep Sequencing Results of NS5B and NS5A of Patients with S282T and/or footprint codon
| Patient No. | Genotype | Treatment | Visit Name | Baseline HCV RNA, IU/mL | 282 codon (Amino Acid) Frequency | NS5B RASs Other Than S282T (Frequency) | NS5A RASs (Frequency) |
|---|---|---|---|---|---|---|---|
| 1 | 2b | SOF monotherapy, 12 weeks | Baseline | 23,600,000 | AGU (S) 54.9%; AGC (S) 44.8% | None | ND |
| 4 weeks posttreatment | 21,700 | ACU (T) >99% | None | ND | |||
| 8 weeks posttreatment | 647,000 | AGU (S) 68%; UCU (S) 4%; ACU (T) 27% | None | ND | |||
| 12 weeks posttreatment | 8,140,000 | AGU (S) 90%; UCU (S) 8% | None | ND | |||
| 24 weeks posttreatment | 11,400,000 | AGT (S) 56.7%; UCU (S) 40.6% | None | ND | |||
| 48 weeks posttreatment | 24,300,000 | AGU (S) 77%; UCU (S) 23% | None | ND | |||
| 2 | 1b | SOF monotherapy, 8 weeks | Baseline | 57,700,000 | AGC (S) 99.0% | None | ND |
| 8 weeks posttreatment | 107,000 | ACC (T) >99% | None | ND | |||
| 3 | 1a | LDV/SOF, 8 weeks | Baseline | 2,940,000 | AGC (S) >99% | None | L31M (25.5%) |
| 8 weeks posttreatment | UCC (S) 8.4%; ACC (T) 91.2% | None | Q30L (4.5%); L31M (>99%); Y93H (96.7%) | ||||
| 10 weeks posttreatment | 1,879,337 | UCC (S) 88.5%; ACC (T) 8.0%; AGC (S) 3.2% | None | Q30L (3.5%); L31M (94.4%); L31V (4.7%); Y93H (98.2%) | |||
| 4 | 1a | LDV/SOF, 24 weeks | Baseline | 2,520,000 | AGC (S) >99% | None | M28T (>99%); Q30R (>99%) |
| 4 weeks posttreatment | 2,610,000 | ACC (T) 1.7%; AGC (S) 97.9% | None | M28T (>99%); Q30R (>99%) | |||
| 6 weeks posttreatment | 4,330,000 | AGC (S) 99.0% | None | M28T (>99%); Q30R (>99%) | |||
| 12 weeks posttreatment | 3,860,000 | AGC (S) >99% | None | M28T (>99%); Q30R (>99%) | |||
| 5 | 1a | LDV/SOF, 24 weeks | Baseline | 5,170,000 | AGC (S) >99% | None | M28V (8.1%); Q30K (10.1%); Q30R (3.8%); Q30T (73.9%) |
| Week 18 | 33,000 | ACC (T) >99% | L159F (97.7%) | K24N (>99%); Q30K (>99%) | |||
| Week 20a | 625,000 | ACC (T) 98.8% | L159F (99.5%) | K24N (98.0%); Q30K (99.6%) | |||
| 4 weeks posttreatmenta | 1,690,000 | ACC (T) >99% | L159F (97.2%) | K24N (98.7%); Q30K (98.0%) | |||
| 6 | 1a | LDV/SOF, 24 weeks | Baseline | 1,370,000 | AGC (S) >99% | None | Y93N (>99%) |
| 5 weeks posttreatment | 288,000 | UCC (S) 84.6%; ACC (T) 14.5% | None | Y93N (>99%) | |||
| SOF/VEL+VOX, 12 weeks | Baseline of retreatmentb | 4,900,000 | UCC (S) 98.1% | None | Y93N (>99%) | ||
| 7 | 3a | LDV/SOF, 12 weeks | Baseline | 1,037,993 | AGU (S) >99% | None | None |
| 2 weeks posttreatment | 437,353 | AGU (S) 10.1%; ACU (T) 89.7% | None | ND | |||
| 4 weeks posttreatment | 990,822 | AGU (S) 62.0% ACU (T) 37.6% | None | None | |||
| 8 weeks posttreatment | 309,023 | AGU (S) 99.4% | None | None | |||
| 12 weeks posttreatment | 70,894 | AGU (S) 89.9% UCU (S) 9.6% | None | ND | |||
| 8 | 4r | LDV/SOF, 12 weeks | Baseline | AGC (S) >99% | None | L30R (>99%); M31M (>99%) | |
| 4 weeks posttreatment | ACC (T) >99% | None | L30R (>99%); M31M (>99%); Y93C (7.8%) | ||||
| 5 weeks posttreatment | ACC (T) 69.1%; AGC (S) 14.9%; UCC (S) 15.4% | None | ND | ||||
| 9 | 5a | LDV/SOF, 12 weeks | Baseline | AGC (S) >99% | None | L31M (>99%) | |
| 4 weeks posttreatment | ACC (T) 1.6%; AGC (S) 98.1% | None | L31M (>99%) | ||||
| 10 | 6l | LDV/SOF+RBV, 12 weeks | Baseline | 6,093,007 | AGU (S) >99% | None | Q24K (>99%); F28V (>99%); R30A (>99%); T58P (>99%) |
| 12 weeks posttreatment | 933,009 | ACU (T) 98.0%; UCU (S) 1.5% | None | Q24K (>99%); F28V (>99%); R30A (>99%); T58P (>99%) | |||
| 11‡ | 1a | LDV/SOF, 12 weeks | Baseline | AGC (S) | None | Y93F (1.22%); Y93N (9.93%) | |
| 12 weeks posttreatment | UCC (S) | None | Y93N (>99%) |
Footprint codons are shown in bold.
a
Full genome sequencing results.
b
Baseline sample of retreatment was collected 16 months after failure of LDV/SOF treatment. This patient has achieved SVR12 after treatment with SOF/VEL+VOX.
Patient 11, did not have S282T observed at posttreatment but the footprint codon UCC at 12 weeks posttreatment suggests that this patient may have had emergent S282T after an SOF‐based regimen that already had reverted to wild type.
Abbreviations: ND, not done; S, serine; T, threonine.