Drug resistance in antiviral therapy

The introduction of nucleos(t)ide analog therapy has seen the emergence of antiviral drug resistance, which has become the main factor limiting the long-term application of these antiviral agents for patients with chronic hepatitis B. The prevention of resistance requires the adoption of strategies that effectively control virus replication and exploit an understanding of the mechanisms and processes that drive the emergence of drug resistance, namely high replication rates, low fidelity of the hepatitis B virus rt/polymerase, selective pressure of the nucleos(t)ide analog, role of replication space (liver turnover), fitness of the mutant, and genetic barrier to the drug.