Table.
Results of Ultra-deep Sequencing Showing the Evolution of NS5A Resistance-associated Variants over Time.
| Case | point | aa28 | aa30 | aa31 | aa32 | aa54 | aa92 | aa93 |
|---|---|---|---|---|---|---|---|---|
| 1 | Before GLE/PIB | L(99.8%) · M(0.2%) | - | - | deletion (99.8%) | - | - | - |
| After GLE/PIB | - | - | L(99.6%) · V(0.2%) | deletion (99.6%) | - | - | - | |
| Before DCV/ASV/BCV | - | - | L(99.7%) · V(0.2%) | deletion (99.6%) | Q(99.3%) · L(0.4%) | - | - | |
| After DCV/ASV/BCV | L(98.9%) · M(1.0%) | - | L(95.7%) · V(4.2%) | deletion (99.7%) | - | - | - | |
| Before IFN† | L(98.9%) · M(1.0%) | - | L(95.7%) · V(4.2%) | deletion (99.7%) | - | - | - | |
| During IFN | L(99.4%) · M(0.5%) | - | L(91.1%) · V(8.8%) | deletion (99.5%) | - | - | - | |
| 2 | Before DCV/ASV | L(49.9%) · M(49.8%) | Q(99.9%) | - | - | Q(66%) · H(33.8%) | T(99.7%) | - |
| After DCV/ASV | T(98.6%) · M(1.4%) | Q(99.8%) · R(0.2%) | - | - | H(99.8%) | K(99.9%) | - | |
| Before LDV/SOF | T(28.7%) · M(71.2%) | E(49.9%) · Q(46.6%) · R(2.1%) · L(1.2%) | - | - | H(98.3%) · Y(1.7%) | K(40.3%) · E(35%) · T(21.7%) · N(2.3%) · Q(0.3%) | - | |
| After LDV/SOF | M(99.7%) | E(99.4%) · G(0.3%) | - | - | H(99.8%) | K(99.6%) · A(0.1%) | - | |
| Before GLE/PIB | M(99.8%) | E(98.8%) · D(0.8%) · G(0.1%) | L(99%) · C(0.8%) | - | H(99.9%) | K(70.4%) · T(29.5%) | - | |
| After GLE/PIB | M(99.8%) | E(99.4%) · G(0.3%) | - | - | H(99.7%) | K(99.6%) · A(0.2%) · R(0.2%) | - |
Substituted amino acids are shown by standard single-letter codes, and frequencies relative to the total coverage by ultra-deep sequencing are also presented.
Dashes indicate amino acids of L28, R30, L31, P32, Q54, P58, A92, and Y93.
†The result before IFN was similar to that after DCV/ASV/BCV.
aa: amino acid, ASV: asunaprevir, BCV: beclabuvir, DCV: daclatasvir, GLE: glecaprevir, IFN: interferon, LDV: ledipasvir, NS: non-structural protein, PIB: pibrentasvir, SOF: sofosbuvir