01 抗病毒药物耐药与影响因素幻灯片.pptVIP

置换对病毒生存率的影响 耐药置换经常会使病毒复制率降低 Tenney DJ, et al. Antimicrob Agents Chemother. 2004;48:3498-07 野生型 LVDr 病毒 (V173L, L180M, M204V) ETVr 病毒 (I169T, V173L, L180M, M204V, M250V 2 3 4 5 6 0 1 2 3 4 5 pg HBV DNA/RLU (106) 转染后天数 谢 谢！ * 对于所有抗病毒药物，强大的抑制病毒能力与无耐药发生直接相关，因为病毒在一个很低的复制水平就能选择产生耐药突变。 初期在土拨鼠模型中ETV治疗14月和36月，持续抑制病毒DNA至不可测水平，结果既没有发生病毒学反弹也无耐药的证据。 为明确临床研究中ETV持续抑制病毒复制的能力是否可导致良好的耐药特性，需对耐药性进行全面评价，包括体外和体内研究，以及超过1500名使用ETV治疗的临床样本量。 For all antivirals, there is direct relationship between potent viral suppression and absence of viral resistance emergence, because viruses require a minimal threshold level of replication to select for resistant variants. Sustained suppression of viral DNA at undetectable levels in the woodchuck model described earlier resulted in an absence of virologic rebound and no evidence of resistance over the 14 and 36 month treatment periods. To ascertain whether the potent and sustained suppression of viral replication achieved by ETV in clinical studies results in a favorable resistance profile, a comprehensive resistance evaluation was conducted that included in vitro and in vivo studies, along with characterization of over 1500 clinical samples from ETV treated patients. (SLIDE CLICK) * * 对于所有抗病毒药物，强大的抑制病毒能力与无耐药发生直接相关，因为病毒在一个很低的复制水平就能选择产生耐药突变。 初期在土拨鼠模型中ETV治疗14月和36月，持续抑制病毒DNA至不可测水平，结果既没有发生病毒学反弹也无耐药的证据。 为明确临床研究中ETV持续抑制病毒复制的能力是否可导致良好的耐药特性，需对耐药性进行全面评价，包括体外和体内研究，以及超过1500名使用ETV治疗的临床样本量。 For all antivirals, there is direct relationship between potent viral suppression and absence of viral resistance emergence, because viruses require a minimal threshold level of replication to select for resistant variants. Sustained suppression of viral DNA at undetectable levels in the woodchuck model described earlier resulted in an absence of virologic rebound and no evidence of resistance over the 14 and 36 month treatment periods. To ascertain whether the potent and sustained suppression of viral replication achieved by ETV in clinical studies results in a favorable