Lamivudine, adefovir and tenofovir exhibit long‐lasting anti‐hepatitis B virus activity in cell culture

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Abstract
In this work, we investigated the anti‐hepatitis B virus (HBV) activity of lamivudine, adefovir, tenofovir, penciclovir and lobucavir after short‐term (i.e. 24 or 48 h) or continuous (9 days) exposure of the HBV‐containing cell line, HepG2 2.2.15, to these drugs. Lamivudine maintained significant anti‐HBV activity when added for only 24 or 48 h to the cell cultures compared to when the drug was present for the whole period (9 days) on the cells, i.e. 50% effective concentration (EC50) values for the inhibition of HBV DNA synthesis were 0.07 ± 0.02 μg ml−1 after 24 h of incubation, 0.02 ± 0.01 μg ml−1 after 48 h of incubation and 0.0016 ± 0.001 μg ml−1 after 9 days of incubation. Similarly, the nucleoside phosphonate analogues, adefovir and tenofovir, retained significant anti‐HBV activity when added for only a short period of time to the cells. The EC50 values were 12 ± 1 μg ml−1 (24 h) and 1.0 ± 0.2 μg ml−1 (48 h) vs 0.003 ± 0.001 μg ml−1 (9 days) for adefovir, and 6.5 ± 1.1 μg ml−1 (24 h) and 0.8 ± 0.1 μg ml−1 (48 h) vs 0.03 ± 0.02 μg ml−1 (9 days) for tenofovir. In contrast, penciclovir and lobucavir lost most of their anti‐viral activity when present on the cells for 48 h or less.