HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

Model Status

This model is currently non-functional (unsuitably constrained).

Model Structure

HIV-1 replication in vivo occurs continuously at high rates. Experimental studies have shown that when a protease inhibitor is administered to infected individuals, plasma concentrations of HIV-1 decreased exponentially. This observed decrease was due to the clearance of free virions from the plasma, and also the loss of virus producing cells. To better understand the kinetics of these two processes, Perelson et al. monitored the viral load of five HIV-1-infected patients after the administration of a protease inhibitor and they tried to simulate these observations using a mathematical model of viral kinetics.

A schematic representation of this mathematical model can be seen in the figure below. The authors assumed that HIV-1 infects target CD4⁺ lymphocytes to become productively infected cells. After the protease inhibitor ritonavir was administered, there was an initial delay period before the exponential decline in plasma viral RNA occurred. The mathematical model was used to analyse the experimental data. Perelson et al. discovered that the rate of total HIV-1 production was surprisingly high at 10.3 * 10⁹ virions per day. This, together with other findings, provided them with a clear image of HIV-1 pathogenesis, and also gave them the theoretical principles to guide the development of therapeutic treatment approaches.

The complete original paper reference is cited below:

HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time, Alan S. Perelson, Avidan U. Neumann, Martin Markowitz, John M. Leonard, and David D. Ho, 1996, Science , 271, 1582-1586. (Full text (HTML) and PDF versions of the article are available on the Science website.) PubMed ID: 8599114

Schematic summary of the dynamics of HIV-1 infection in vivo. Shown in the centre is the cell-free virion population that is sampled when the virion load in the plasma is measured.