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长期应用拉米夫定的患者有部分出现耐药性 ,研究发现耐药性的产生与病毒多聚酶编码区变异相关。变异导致酪氨酸 蛋氨酸 天门冬氨酸 天门冬氨酸基序中的蛋氨酸突变为异亮氨酸或缬氨酸 ,后者常伴有第 52 8位亮氨酸被蛋氨酸替换。治疗起始时有高水平血清HBVDNA滴度的患者和在应用免疫抑制剂的患者或有前C区变异株感染的患者的变异发生率高。耐药性的发生机制与变异株产生后导致拉米夫定渗入DNA链的能力减低有关。病毒发生变异后可继续拉米夫定治疗。联合用药有可能降低变异的发生率。
Long-term use of lamivudine in patients with part of the emergence of drug resistance, the study found that the emergence of drug resistance and mutation of the viral polymerase coding region. Mutations result in the mutation of the methionine in the tyrosine-methionine aspartate motif to isoleucine or valine, which is often accompanied by the substitution of leucine at position 528 for methionine. Patients who had high levels of serum HBVDNA titer at the start of treatment had a high rate of mutation in patients who received immunosuppressive agents or in patients with pre-C-region mutations. The mechanism of drug resistance is related to the diminished ability of lamivudine to penetrate into the DNA strand after the mutant is produced. After the mutation of the virus can continue lamivudine treatment. Combination therapy may reduce the incidence of mutation.