Wodarz, Nowak, 1999

Model Status

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

Model Structure

Despite significant improvements in antiviral therapy for HIV-infected patients, there are still problems such as negative side effects and viral resistance. In addition, long-lived infected cells make it unlikely that combination therapy alone will be able to eradicate HIV from infected patients. Consequently there is a considerable interest in finding a therapy regime which reduces viral loads and restimulates immune responses.

There is clinical evidence to suggest that antiviral immune responses play an important role in determining virus load and the rate of disease progression in infected patients. Good CD4- and CD8-mediated immune responses against HIV, together with a low virus load, mean that patients can carry the disease for long periods without the severity of the infection increasing.

In the study described here, Wodarz and Nowak develop a mathematical model to study the interaction between HIV and the immune system. They use the results of model simulations to analyse how specific antiviral treatment regimes can lead to the establishment of effective immune responses and long-term control of HIV. Their model contains four variables: uninfected CD4⁺ T cells, infected CD4⁺ T cells, cytotoxic T lymphocyte (CTL) precursors, and CTL effectors (see the figure below).

The complete original paper reference is cited below:

Specific therapy regimes could lead to long-term immunological control of HIV, Dominik Wodarz and Martin A. Nowak, 1999, Proceedings of the National Academy of Sciences, USA , 96, 14464-14469. (Full text (HTML) and PDF versions of the article are available on the Proceedings of the National Academy of Sciences, USA website.) PubMed ID: 10588728

Schematic diagram of a model of the interaction between HIV and the immune system.

Model simulations suggest that an efficient CTL memory response (defined as long-term persistence of CTL precursors in the absence of antigen) is required to control HIV. Infection and depletion of CD4⁺ T helper cells interfere with CTL memory generation, resulting in persistent viral replication and disease progression. Antiviral drug therapy during the primary infection can enable the development of CTL memory. In chronically infected patients, specific treatment schedules can lead to a re-establishment of CTL memory.