Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis

被引:384
作者
Ramratnam, B
Bonhoeffer, S
Binley, J
Hurley, A
Zhang, LQ
Mittler, JE
Markowitz, M
Moore, JP
Perelson, AS
Ho, DD
机构
[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[2] ETH Zentrum NW, Zurich, Switzerland
[3] Friedrich Miescher Inst, CH-4002 Basel, Switzerland
[4] Los Alamos Natl Lab, Los Alamos, NM USA
关键词
D O I
10.1016/S0140-6736(99)02035-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:1782 / 1785
页数:4
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