TABLE 3.
Effects of selected anti-HBV drugs on replication of HBV mutants derived from the viral quasispecies of chronically infected patientsa
| HBV strainb | LAM
|
ADV
|
TDF
|
ETV
|
PMEO-DAPym
|
|||||
|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (μM) | FRc | EC50 (μM) | FR | EC50 (μM)d | FR | EC50 (μM)d | FR | EC50 (μM)d | FR | |
| wt 1 | 0.64 ± 0.17d | 1 | 13.6 ± 4.08d | 1 | 13.6 ± 4 | 1 | 0.09 ± 0.03 | 1 | 4.4 ± 0.5 | 1 |
| wt 2 | 0.1 ± 0.2e | 1 | 10 ± 3e | 1 | 25 ± 7.1 | 1 | 0.06 ± 0.01 | 1 | 5.6 ± 1.0 | 1 |
| LAMr | ||||||||||
| rtL180M/M204V | >100e | >1,000 | 15 ± 6e | 1.5 | 27 ± 10 | 1.1 | 10.5 ± 2.2 | 175 | 5.3 ± 0.88 | 0.9 |
| rtL180M/A181V | 80 ± 9e | 800 | 27 ± 16e | 2.7 | 36 ± 13 | 1.4 | 1.5 ± 0.6 | 28 | 27 ± 10.3 | 4.8 |
| rtV173L/L180M/M204V | >100d | >156 | 9.8 ± 2.5d | 0.7 | 16 ± 5.8 | 1.2 | 3.7 ± 1.4 | 43 | 4.1 ± 0.4 | 0.9 |
| LAMr +ADVr | ||||||||||
| rtV173L/L180M/A181V | 100 ± 5e | 1,000 | 48 ± 19e | 4.8 | 42 ± 8.1 | 1.6 | 2.75 ± 1.2 | 50 | 24 ± 4.5 | 4.3 |
| rtV173L/L180M/A181V/M204V | >100e | >1,000 | 40 ± 20e | 4.0 | 45 ± 21.3 | 1.8 | ≥50 ± 15.9 | ≥800 | 18 ± 7.0 | 3.2 |
| rtV173L/L180M/A181V/M204V/N236T | >100e | >1,000 | 77 ± 20e | 7.7 | 46 ± 18.3 | 1.8 | 25.4 ± 5.5 | 461 | 12 ± 3.0 | 2.1 |
| rtV173L/L180M/A181V/N236T | >100e | >1,000 | >100e | >10 | 28 ± 5.6 | 1.1 | 0.5 ± 0.14 | 9.0 | 29 ± 5.3 | 5.1 |
| ETVr | ||||||||||
| rtL180M/S202G/M204V | >100d | >156 | 15 ± 4.5d | 1.1 | 27 ± 9.8 | 2 | 18 ± 8.7 | 210 | 4.5 ± 0.9 | 1.0 |
LAM, lamivudine; ADV, adefovir; TDF, tenofovir; ETV, entecavir.
LAMr, lamivudine resistant; LAMr + ADVr, lamivudine-adefovir resistant; ETVr, entecavir resistant.
FR, fold resistance, which is equal to (mutant EC50)/(wt EC50). For mutants rtV173L/L180M/M204V and rtL180M/S202G/M204V, the corresponding wt strain is wt1 (genotype H) and the fold resistance is equal to (mutant EC50)/(wt1 EC50). For the other mutants, the corresponding wt strain is wt2 (genotype E) and the fold resistance is equal to (mutant EC50)/(wt2 EC50).
Values represent the means of at least three independent experiments, each of which was performed in triplicate. For each experiment, the drug-resistant HBV strains and their corresponding wt strains were treated simultaneously with the same range of drug concentrations (from 0 to 100 μM for PMEO-DAPym, lamivudine, adefovir, and tenofovir; from 0 to 10 μM for entecavir), and all the samples were extracted and analyzed by Southern blotting, in parallel.
The data were reported previously (24).