Estimation of the Initial Viral Growth Rate and Basic Reproductive Number during Acute HIV-1 Infection
Estimation of the Initial Viral Growth Rate and Basic Reproductive Number during Acute HIV-1 Infection
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DOI：
10.1128/jvi.00127-10
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Perelson, Alan S.
中科院分区：
文献类型：
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作者：
Ribeiro, Ruy M.;Qin, Li;Perelson, Alan S.
在初次感染期间，血浆中HIV-1颗粒的数量迅速增加，达到峰值，然后下降，直到达到设定点水平。了解原发感染的动力学及其对慢性感染的影响，对于确定HIV的早期发病机制非常重要。我们研究了47例通过血浆捐献筛查确定的极早期HIV-1感染者的病毒动力学。我们计算了病毒载量增加的速度以及个体之间该参数的变化。我们还估计了基本繁殖率，即当靶细胞不受限制时，感染细胞在感染开始时产生的新感染细胞的数量。初始病毒倍增时间的中位数为0.65天，四分位数范围为0.56 - 0.91天。中位基本生殖比为8.0，四分位数范围为4.9至11。在15例患者中，我们还观察到血浆病毒的峰后衰减，发现病毒衰减的中位速率为0.60天（-1），对应于1.2天的半衰期。中位峰值病毒载量为5.8 log（10）HIV-1 RNA拷贝/ml，在病毒可通过检测定量后14天达到，检测下限为50拷贝/ml。这些结果更好地表征了急性HIV感染的早期血浆病毒动力学。它们还更好地定义了免疫反应（或治疗干预）必须克服的挑战，以在早期阶段击败艾滋病毒。
During primary infection, the number of HIV-1 particles in plasma increases rapidly, reaches a peak, and then declines until it reaches a set point level. Understanding the kinetics of primary infection, and its effect on the establishment of chronic infection, is important in defining the early pathogenesis of HIV. We studied the viral dynamics of very early HIV-1 infection in 47 subjects identified through plasma donation screening. We calculated how fast the viral load increases and how variable this parameter is among individuals. We also estimated the basic reproductive ratio, the number of new infected cells generated by an infectious cell at the start of infection when target cells are not limiting. The initial viral doubling time had a median of 0.65 days with an interquartile range of 0.56 to 0.91 days. The median basic reproductive ratio was 8.0 with an interquartile range of 4.9 to 11. In 15 patients, we also observed the postpeak decay of plasma virus and found that the virus decay occurred at a median rate of 0.60 day(-1), corresponding to a half-life of 1.2 days. The median peak viral load was 5.8 log(10) HIV-1 RNA copies/ml, and it was reached 14 days after the virus was quantifiable with an assay, with a lower limit of detection of 50 copies/ml. These results characterize the early plasma viral dynamics in acute HIV infection better than it has been possible thus far. They also better define the challenge that the immune response (or therapeutic intervention) has to overcome to defeat HIV at this early stage.