Department of R&MD, North Melbourne, Victoria, Australia.
Clin Liver Dis. 2010 Aug;14(3):439-59. doi: 10.1016/j.cld.2010.05.004.
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.
核苷（酸）类似物治疗的引入带来了抗病毒药物耐药性的出现，这已成为限制这些抗病毒药物在慢性乙型肝炎患者中长期应用的主要因素。耐药性的预防需要采取有效控制病毒复制的策略，并利用对耐药性产生机制和过程的了解，即乙型肝炎病毒 rt/聚合酶的高复制率、低保真度、核苷（酸）类似物的选择压力、复制空间（肝周转率）的作用、突变体的适应性以及药物的遗传屏障。
