Analysis of hepatitis B viral load decline under potent therapy: Complex decay profiles observed
Analysis of hepatitis B viral load decline under potent therapy: Complex decay profiles observed
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DOI：
10.1053/jhep.2001.28509
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发表时间：
2001-11-01
期刊：
影响因子：
13.5
通讯作者：
Perelson, AS
中科院分区：
文献类型：
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作者：
Lewin, SR;Ribeiro, RM;Perelson, AS
我们使用了一种新的实时聚合酶链反应（PCR）为基础的检测，是敏感的，有一个宽的动态线性范围，并具有高度的可重复性，以量化B型肝炎病毒（HBV）DNA在感染的个人接受有效的抗病毒治疗的血清。此外，我们在治疗开始后频繁测量病毒载量，并保持随访约12周。为了分析这些数据，我们使用了一种新的HBV衰减模型，该模型考虑到现有的药物治疗不能完全阻断dc novo感染以及感染细胞的非细胞溶解性损失的可能性。在治疗开始时，平均延迟1.6天，随后是血浆HBV DNA的双相或多相衰减。第一阶段的斜率变化很大，其中一个个体具有快速衰减，对应于1小时的病毒体半衰期，但其他个体的半衰期长达92小时。个体要么有缓慢的第二阶段下降（t（1/2）= 7.2 +/- 1.2天），要么有平坦的第二阶段。一些个体表现出复杂的“阶梯模式”的衰变，具有病毒DNA下降的进一步阶段和病毒载量几乎没有变化的阶段。
We used a new real-time polymerase chain reaction (PCR)-based assay that is sensitive, has a wide dynamic linear range, and is highly reproducible to quantify hepatitis B virus (HBV) DNA in the serum of infected individuals undergoing potent antiviral therapy. In addition, we made frequent measurements of viral load after initiation of treatment and maintained follow-up to about 12 weeks. To analyze the data we used a new model of HBV decay, which takes into account that existing drug treatments do not completely block dc novo infection and the possibility of noncytolytic loss of infected cells. On initiation of therapy, there was a mean delay of 1.6 days followed by a biphasic or muliphasic decay of plasma HBV DNA. The slope of the first phase varied considerably, with one individual having rapid decay, corresponding to a virion half-life of I hour, but others showing half-lives of up to 92 hours. Individuals either had a slow second-phase decline (t(1/2) = 7.2 +/- 1.2 days) or a flat second phase. Some individuals exhibited a complex "staircase pattern" of decay, with further phases of viral DNA decline and phases with little change in viral load.