<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : wodarz_model_1999.xml
CREATED : 10th December 2003
LAST MODIFIED : 10th December 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Wodarz and Nowak's 1999 mathematical model of immunological control of HIV.
CHANGES:
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the Interaction between HIV and the Immune System</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
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 <emphasis>and</emphasis> restimulates immune responses.
</para>
<para>
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.
</para>
<para>
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<superscript>+</superscript> T cells, infected CD4<superscript>+</superscript> T cells, cytotoxic T lymphocyte (CTL) precursors, and CTL effectors (see the figure below).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.pnas.org/cgi/content/abstract/96/25/14464">Specific therapy regimes could lead to long-term immunological control of HIV</ulink>, Dominik Wodarz and Martin A. Nowak, 1999, <ulink url="http://www.pnas.org/">
<emphasis>Proceedings of the National Academy of Sciences, USA</emphasis>
</ulink>, 96, 14464-14469. (<ulink url="http://www.pnas.org/cgi/content/full/96/25/14464">Full text (HTML)</ulink> and <ulink url="http://www.pnas.org/cgi/reprint/96/25/14464.pdf">PDF</ulink> versions of the article are available on the <emphasis>Proceedings of the National Academy of Sciences, USA</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10588728&dopt=Abstract">PubMed ID: 10588728</ulink>
</para>
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<title>cell diagram</title>
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</mediaobject>
<caption>Schematic diagram of a model of the interaction between HIV and the immune system.</caption>
</informalfigure>
<para>
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<superscript>+</superscript> 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.
</para>
</sect1>
</article>
</documentation>
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<dc:title>
Wodarz and Nowak's 1999 mathematical model of immunological control of
HIV.
</dc:title>
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Proceedings of the National Academy of Science, USA
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Specific therapy regimes could lead to long-term immunological
control of HIV
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<bqs:volume>96</bqs:volume>
<bqs:first_page>14464</bqs:first_page>
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<dcterms:W3CDTF>1999-12-07</dcterms:W3CDTF>
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<vCard:Given>Martin</vCard:Given>
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<vCard:Other>A</vCard:Other>
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<dcterms:W3CDTF>2003-12-10</dcterms:W3CDTF>
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<vCard:Given>Catherine</vCard:Given>
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The University of Auckland, Bioengineering Institute
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