Nelson, Murray, Perelson, 2000

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

In recent years, clinical research together with mathematical modelling has enhanced our understanding of HIV-1 infection dynamics. For example, the introduction of a new class of antiretroviral drugs called protease inhibitors has helped to define the kinetic parameters underlying HIV-1 infection. However, many of the mathematical models that have been developed have incorrectly assumed that drug treatments are 100 percent effective, and that upon infection, a cell immediately begins to produce virus.

In HIV-1 infection, the virus life cycle plays a crucial role in disease progression. The binding of a viral particle to a receptor on a target T-cell initiates a cascade of of events that can lead to the targeted cell becoming productively infected, that is, producing new virus (see the figure below). There is a significant time delay between initial viral entry into a cell and subsequent viral production.

In 2000, Nelson et al. published a mathematical model of HIV-1 pathogenesis that included an intracellular delay in the initiation of virus production. Their model also allowed for the fact that the effects of drugs can be less than perfect. Analysis showed that when drug efficacy is less than perfect, as is frequently the case in vivo, the predicted rate of decline in plasma virus concentration depends on three factors: the death rate of infected, virus producing T-cells, the efficacy of the drug therapy, and the length of the time delay between infection of a T-cell and virus production. From their model, Nelson et al. suggest that previous estimates of infected cell loss rates may be unrealistic and could be improved upon by considering more realistic models of viral infection.

The complete original paper reference is cited below:

A model of HIV-1 pathogenesis that includes an intracellular delay, Patrick W. Nelson, James D. Murray, and Alan S. Perelson, 2000, Mathematical Biosciences , 163, 201-215. (A PDF version of the article is available for Journal Members on the Mathematical Biosciences journal website.) PubMed ID: 10701304

A schematic diagram showing the cascade of events triggered by the binding of a HIV-1 virus particle to a receptor on a target T-cell.