TABLE 1.
Prevalence of HCV GT NS3, NS5A, and NS5B polymorphisms at clinically relevant residue positions associated with drug resistance
| Polymorphisms (n) ina: | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NS3 sequences (n = 104) | NS5A sequences (n = 130) | NS5B sequencesb (n = 104) | ||||||||||||||
| V36 | Y56 | K80 | A156 | D168 | I170 | L28 | R30 | L31 | T58 | T93 | L159 | S282 | L392 | V421 | V494 | P495 |
| V (78) | Y (93) | Q (81) | A (103) | D (102) | V (70) | V (52) | S (58) | L (126) | P (65) | T (109) | L (100) | S (102) | L (96) | V (103) | A (77) | P (103) |
| L (20) | F (11) | K (22) | V (1) | E (2) | I (33) | L (36) | R (38) | I (2) | T(46) | S (18) | F (3) | C (1) | I (8) | A (1) | V (25) | L (1) |
| I (6) | L (1) | A (1) | F (14) | A (28) | M (2) | G (5) | I (2) | ? (1) | ? (1) | M (2) | ||||||
| T (13) | N (4) | S (6) | ? (1) | |||||||||||||
| A (6) | E (1) | A (4) | ||||||||||||||
| M (6) | T (1) | ? (1) | ||||||||||||||
| ? (2) | L (2) | |||||||||||||||
| G (1) | L/Pc (1) | |||||||||||||||
The first row depicts the GT-6a consensus sequence (determined from alignment of 24 NS3, 36 NS5A, and 24 NS5B sequences). Underlining indicates polymorphisms previously shown to be associated with DAA resistance (21, 33, 35–37, 48); ?, undefined polymorphism. Only GT-6a reference polymorphisms were observed at NS3 (T54, V55, and R155), NS5A (P29 and P32), and NS5B (V321 and A499) resistance-associated residue positions. NS5A-A92P was detected in 1/130 NS5A sequences.
BCV-associated RASs include L392I, A421V, V494A, L495L/S, and A499T; SOF-associated RASs were found at L159F, S282T, and V321I.
One patient-derived NS5A sequence had a mixture of polymorphisms detected at T58. Each of these polymorphisms (L58 and P58) represented ≥15% of the viral population.