Author/Authors :
Bharat Ramratnam، نويسنده , , Sebastian Bonhoeffer، نويسنده , , James Binley، نويسنده , , Arlene Hurley، نويسنده , , Linqi Zhang، نويسنده , , John E Mittler، نويسنده , , M Markowitz، نويسنده , , John P Moore، نويسنده , , Alan S. Perelson and Gérard Weisbuch، نويسنده , , David D Ho، نويسنده ,
Abstract :
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 log10-10·2 log10 particles for HIV-1 and 11·6 log10-13·0 log10 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.