Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis
复制标题
DOI：
10.1016/s0140-6736(99)02035-8
复制
发表时间：
1999-11-20
期刊：
影响因子：
168.9
通讯作者：
Ho, DD
中科院分区：
文献类型：
--
作者：
Ramratnam, B;Bonhoeffer, S;Ho, DD
背景在慢性HIV-1感染中，病毒产生和清除之间存在动态平衡。游离病毒体的半衰期可以通过用抗逆转录病毒药物抑制病毒体的产生并模拟血浆HIV-1 RNA的下降来估计。为了定义HIV-1和丙型肝炎病毒（HCV）的动力学，我们使用血浆分离术，以增加病毒粒子清除暂时离开病毒粒子productioninduced.Methods血浆病毒载量测定前，期间，和后的四个HIV-1感染的患者，其中两人也合并感染HCV。用非线性最小二乘法拟合血浆病毒载量与病毒动力学模型，计算病毒粒子清除速率，结果病毒粒子清除速率常数为0.0063/min HIV-1为0.0038/min（9.1/天）至0.025/min（36.0/天;半衰期28-110 min），HCV为0.0038/min（5.5/天）至0.0069/min（9.9/天;半衰期100-182 min）。这些值提供了HIV-1的9.3 log（10）-10.2 log（10）粒子和HCV的11.6 log（10）-13.0 log（10）粒子的每日粒子产生的估计值。解释我们的发现证实HIV-1和HCV的产生和清除非常迅速。对HIV-1清除率的新估计比以前的估计高出10倍，而HCV清除率与以前的估计相似。
Background In chronic HIV-1 infection, dynamic equilibrium exists between viral production and clearance. The half-life of free virions can be estimated by inhibiting virion production with antiretroviral agents and modelling the resulting decline in plasma HIV-1 RNA. To define HIV-1 and hepatitis C virus (HCV) dynamics, we used plasma apheresis to increase virion clearance temporarily while leaving Virion production unaffected.Methods Plasma virus loads were measured frequently before, during, and after apheresis in four HIV-1-infected patients, two of whom were also co-infected with HCV. Rates of virion clearance were derived by non-linear least-square fitting of plasma virus load to a model of Viral dynamics.Findings Virion clearance rate constants were 0.0063/min (9.1/day) to 0.025/min (36.0/day; half-life 28-110 min) for HIV-1 and 0.0038/min (5.5/day) to 0.0069/min (9.9/day; half-life 100-182 min) for HCV. These values provided estimates of daily particle production of 9.3 log(10)-10.2 log(10) particles for HIV-1 and 11.6 log(10)-13.0 log(10) particles for HCV.Interpretation Our findings confirm that HIV-1 and HCV are produced and cleared extremely rapidly. New estimates for HIV-1 clearance are up to ten times higher than previous ones, whereas HCV clearance is similar to previous estimates.