HIV infection is characterized by a dynamic equilibrium between virus production and clearance. Previously, the t1/2 of plasma virions has been estimated to be <6 hours by mathematical analyses of the decline in plasma viremia (PV) following antiviral therapy. To define the clearance rate of HIV particles with greater precision, we utilized plasma apheresis to perturb the dynamic equilibrium in 4 infected, untreated subjects (PV of 10⁴ to 2 x 10⁵ copies/ml), 2 of whom were co-infected by HCV (PV of 4 to 69 x 10⁶ copies/ml). The apheresis procedure abruptly increased particle clearance by an amount that we set experimentally (approximately 110 ml/min) for 1-2 hours, presumably without affecting HIV production. Thus, the magnitude of the decrease in plasma viremia during apheresis reflects the added clearance rate mediated by the procedure relative to that mediated by the host. Frequent determinations of the levels of PV before, during and after apheresis were made by bDNA assays. These results were fitted to an established mathematical model of viral dynamics (see example in Fig.), thereby yielding HIV particle t1/2 values of 39 to 109 minutes. Using the same approach, HCV particle t1/2 was found to be 100 to 182 minutes. These clearance half lives, in turn, allowed us to calculate the daily virion production in these subjects to be 4 to 30 billions for HIV and 0.4 to 10 trillion for HCV. (Figure: see text).

1999-01-31
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