Table 3.
Mutations in hepatitis B virus (HBV) reverse-transcriptase genes detected by direct polymerase chain reaction (PCR) sequencing and by ultra-deep pyrosequencing (UDPS) of 20 samples from 11 patients infected with HBV and treated with nucleoside and/or nucleotide reverse-transcriptase inhibitors (NRTIs).
| Subject identifier,a sample no. | HBV genotype | NRTI(s)b (no. of months administered) | Mutations detected by direct PCR | Additional mutations detected by UDPSc (sample reads detected, %) |
|---|---|---|---|---|
| G1 | B | 3TC (27), ADV (21), ETV (7) | N131S, L180M, M204V, A222T, R274K | … |
| A6 | D | 3TC (12), ETV (10), ETV and ADV (4) | L91L/I, L180L/M, M204M/V/I, S219A, L229L/V, I266K | L80V (1.5), S202G (9.9),V207L (3.1) |
| C5 | B | ADV and 3TC (3), ADV (17), none (19) | T38T/A, L91L/I, N118N/T, N131N/D | T16I (4.5), N53I/V (15, 4.6), T54N (4.6), H124D (15), N134D (16), Y141F (8.1), A222T (8.3), N236T (6.6), V253I (2.1) |
| CM | C | 3TC (24), 3TC and ADV (15), none (7) | L267Q, N337H | … |
| HTT | B | 3TC (38) | E1D, N53E, S117P, N124H, N134D, L180M, A181V, M204V, A222A/T, T259S, M271S, K275Q, G295A, Q334L, L336M | L29V (2.8), N33I (6.9), P325S (3.4), L336I (2.1) |
| 7774 | ||||
| 1 | A | None | A7D, I53I/N/V/D, T54T/N, I103V, S116S/T, L129M, S143S/T, I163V, L217R, S219/SA, V253I | A7N (15), H35N (4.2), I53S (2.7), D134E (6.0), R138K (8.9), V207I (8.8), N238H (7.7), H271Q (4.3), M336L (10) |
| 2 | A | 3TC (12) | A7D, I103V, L129M, I163V, L180L/M, M204I, L217R, L229L/V, V253I, H271Q, M336L | I53S (12), S116T (7.7), T184S (2.7), A200V (7.7), M204V (8.0), S219A (9.9) |
| 3 | A | 3TC (24) | A7D, I53I/N, I103V, L129M, S116S/T, S143S/T, I163V, L180M, M204V, V207V/I/M, L217R, S219S/A, V253I | I53S (3.9), N131H (2.5), S135A (18), T184S (2.2), M204I (9.3), L229V (5.4), H271Q (8.0), S332R (15), M336L (9.0) |
| 16375 | ||||
| 1 | A | 3TC (1) | A7D, I53V, V112I, A113A/T, S117S/C, L129M, L140L/I, M145M/L, I163V, V173V/L, L217R, S219S/A, V253I | L115V (3.4), N122H /S (3.1/2.5), G127R (7.4), I169M (3.9), N248H (15), H271Q (2.6) |
| 2 | A | 3TC (12) | A7D, I53V, V112I, L129M, I163V, V173L, L180M, M204V, L217R, V253I | N33I (2.4), V112L (2.7), N122H (8.4), V207L (6.2), W243R (5.2), N248H (3.5), H271Q (8.3) |
| 3 | A | 3TC (24) | A7D, I53V, V112I, L129M, I163V, V173L, L180M, M204V, L217R, S219S/A, V253I | N33I (4.1), N76K (5.2), N122H (4.0), V207L (2.8), N248H (13), H271Q (3.7), S332R (2.1) |
| 1329 | ||||
| 1 | A | 3TC (41) | A7D, L129M, I163V, L180M, M204V, L217R, S219A, V253I, K333Q | I16T (3.5), I53T (3.4), N123D (13), V173L (5.1), V191I (2.8), M204I (1.6) |
| 2 | A | 3TC (48) | A7D, L129M, I163V, L180M, M204V, L217R, S219A, V253I, K333Q | I16T (11), I53T (5.5), N123D (10), V173L (16), V191I (2.9) |
| 26278 | ||||
| 1 | G | 3TC (48) | A54A/T, I163I/V, L180M, M204M/I/V, V207V/I/M, T266T/K | T7D (3.6), S53I (7.3), V103I (8.4), D118N (5.5), L122N/K (4.8/4.0), D123N (8.9), H124N (9.0), T128A (4.6), L129M (8.8), F151Y (9.6), R153W (9.4), V173L (11), A181T (1.4), V191I (5.2), L217R (6.1), S219A (3.1), L229F (19), V253I (5.7), E263D (5.7), T266V (5.6), Q271H (5.9), T291V (2.6), C332S (7.7) |
| 2 | G | 3TC (48), none (3) | A54A/T, I163I/V, L180M, M204M/I/V, V207V/I/M, T266T/K | T7D (2.3), S53I (7.7), V103I (7.0), D118N (4.6), L122N/K (4.6/2.5), D123N (7.4), H124N (7.3), T128A (4.2), L129M (7.2), F151Y (8.0), R153W (7.8), V173L (13), V191I (5.1), L217R (7.1), S219A (2.4), L229F (18), V253I (5.7), E263D (5.7), T266V (5.6), Q271H (5.6), T291V (2.8), C332S (7.4) |
| 3 | G | 3TC (48), none (3), TDF and FTC (3) | A54A/T, I163I/V, L180M, M204M/I/V, V207V/I/M, T266T/K | T7D (3.2), S53I (6.8), V103I (7.0), D118N (5.4), L122N/K (4.0/3.4), D123N (8.1), H124N (7.0), T128A/M (5.0/7.6), F151Y (8.3), R153W (7.8), V173L (12), V191I (3.3), L217R (5.3), L229F (19), V253I (4.3),E263D (4.2), T266V (4.0), Q271H (4.3), C332S (6.4), M336I (2.7) |
| 4089 | ||||
| 1 | G | 3TC (24), none (12) | T7T/A/D, S53S/I, A54A/T, V103V/I, D118D/N, L122L/H, D123D/N, H124H/N, F151F/Y, E263E/D, T266T/A/I/V, Q267Q/K, Q271Q/H, V278V/I, T291T/V/A/I/M, C332C/S, M336M/L | … |
| 2 | G | 3TC (24), none (12), 3TC (17) | T7T/A, V103V/I, D118D/N, L122L/H, D123D/N, H124H/N, F151F/Y, V173V/L, L180M, M204V, E263E/D, T266T/A/I/V, Q267K/Q, Q271Q/H, V278V/I, T291T/A/I/M/V, C332C/S | T7D (12), S53I (14), A54T (14), V112I (5.2), L229W (12), M336L (14) |
| 3 | G | 3TC (24), none (12), 3TC (36) | V173L, L180M, M204V, Q267K | … |
| 1284 | ||||
| 1 | G | 3TC (43) | V173L, L180M, M204V | T7D (13), S53I (12), A54T (12), V103I (9.1), D118N (10), L122N (10), D123N (9.5), H124N (10), T128N (10), L129M (10), F151Y (8.6), R153W (8.6), I163V (7.0), L217R (8.8), L229F (3.9), V253I (9.2), E263D (9.3), T266V (9.2), Q271H (9.3), T291V (3.9), C332S (11) |
| 2 | G | 3TC (52), none (27) | … | T7D (2.2), S53I (2.8), A54T (2.9), V103I (2.8), D118N (4.1), L122N (3.8), D123N (4.0), H124N (4.1), T128N (3.9), L129M (3.9), F151Y (3.3), R153W (3.5), I163V (4.1), V173L (13), L180M (13), A181T (3.9), M204V (9.0), L217R (2.1), E263D (2.6), C332S (2.8) |
NOTE. Mutations were defined as differences from the consensus genotype sequence. Mutations in bold type are established NRTI-resistance mutations. Underlined mutations have been considered accessory NRTI-resistance mutations. ADV, adefovir; ETV, entecavir; FTC, emtricitabine; NRTI, nucleoside and/or nucleotide reverse-transcriptase inhibitor; TDF, tenofovir; 3TC, lamivudine.
Samples from subjects 1329, 7774, 1284, 26278, 16375, and 4089 were obtained from HIV-infected patients; the remaining patients were HIV-1 seronegative.
NRTIs administered to the patient from whom the sample was obtained. When the data in this column includes “none” as the last or only item, this indicates that the patient was not receiving NRTI therapy at the time the sample was obtained.
Mutations shown are those with a prevalence ≥1.0% at positions known to be associated withNRTI-resistance or prevalence ≥2.0% at any other reverse-transcriptase position.