- Author:
- James Lawson <j.lawson@auckland.ac.nz>
- Date:
- 2009-09-15 12:52:33+12:00
- Desc:
- updated curation status
- Permanent Source URI:
- https://models.cellml.org/workspace/dixit_perelson_2004/rawfile/e0616ca9dbc844168c971634b62cf869a216af8c/dixit_perelson_2004.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : dixit_model_II_2004.xml
CREATED : 12th December 2003
LAST MODIFIED : 12th 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 Dixit and Perelson's 2nd 2004 mathematical model of viral dynamics in the presence of reverse transcriptase inhibitors.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="dixit_perelson_2004_version02" name="dixit_perelson_2004_version02">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the Complex Patterns of Viral Load Decay under Antiretroviral Therapy</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 model is valid CellML but can not be integrated as it is overconstrained. Some variables are not initialised and the value for delta is not contained in the publication.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
When treated with antiretroviral therapy, the plasma viral loads in HIV patients decline in three distinct phases:
</para>
<itemizedlist>
<listitem>
<para>When the treatment is initially administered there is a 6 to 72 hour delay before the viral loads begin to decline;</para>
</listitem>
<listitem>
<para>following this <emphasis>shoulder</emphasis> period viral load decline rapidly for about one week;</para>
</listitem>
<listitem>
<para>finally, viral loads continue to decrease, but at a slower rate.</para>
</listitem>
</itemizedlist>
<para>
In the Dixit and Perelson 2004 publication described here, the authors present a mathematical model that combines pharmacokinetics and viral dynamics and includes intracellular delay. The model of viral dynamics is based on that published by <ulink url="${HTML_EXMPL_PERELSON_MODEL}">Perelson <emphasis>et al.</emphasis>
</ulink> (see <xref linkend="fig_cell_diagram"/> below). To accurately represent the pharmacokinetics they assume a two compartment model consisting of blood and cells. The models of viral dynamics and pharmacokinetics are connected via a parameter which represents drug specific efficacy. Because reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) have very different effects on the duration of the intracellular delay, they have been modelled separately (see <xref linkend="fig_reaction_diagram1"/> and <xref linkend="fig_reaction_diagram2"/>). </para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Complex patterns of viral load decay under antiretroviral therapy: influence of pharmacokinetics and intracelllar delay, Narendra M. Dixit and Alan S. Perelson, 2004,
<emphasis>Journal of Theoretical Biology</emphasis>
, 226, 95-109. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14637059&dopt=Abstract">PubMed ID: 14637059</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="dixit_2004a.png"/>
</imageobject>
</mediaobject>
<caption>Schematic summary of the dynamics of HIV-1 infection <emphasis>in vivo</emphasis>. This model is based on that published by Perelson <emphasis>et al.</emphasis> in 1996.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram1">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram1</title>
</objectinfo>
<imagedata fileref="dixit_2004b.png"/>
</imageobject>
</mediaobject>
<caption>Pharmacokinetics - the two compartment model for protease inhibitors.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram2">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram2</title>
</objectinfo>
<imagedata fileref="dixit_2004c.png"/>
</imageobject>
</mediaobject>
<caption>Pharmacokinetics - the two compartment model for reverse transcriptase inhibitors. The main difference between the models is that RTIs must be phosphorylated within the cell in order to be in their active form.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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</units>
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<unit units="litre" prefix="milli" exponent="-1"/>
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<units name="day">
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<variable units="per_ml" public_interface="out" name="VI"/>
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<variable units="dimensionless" public_interface="in" name="epsilon_PI"/>
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<ci> epsilon_PI </ci>
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<rdf:RDF>
<rdf:Description rdf:about="epsilon_PI">
<dc:title>instantaneous drug efficacy</dc:title>
<dcterms:alternative>non-infectious viral load</dcterms:alternative>
</rdf:Description>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Seq rdf:about="rdf:#citationAuthorsSeq">
<rdf:li rdf:resource="rdf:#author1Vcard"/>
<rdf:li rdf:resource="rdf:#author2Vcard"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#author2VcardN">
<vCard:Given>Alan</vCard:Given>
<vCard:Family>Perelson</vCard:Family>
<vCard:Other>S</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#dce94775-74da-46a3-b668-f848194504e4">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cb2e90cf-8267-4746-a377-b69d2176da09">
<dc:creator rdf:resource="rdf:#d8541a94-3dba-46fa-8de6-c74b880ef203"/>
<rdf:value>This is the CellML description of Dixit and Perelson's 2nd 2004 mathematical model of viral dynamics in the presence of reverse transcriptase inhibitors.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8eed6c27-f49f-4f5f-bbab-b316a7c04b1c">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>
<rdf:Bag>
<rdf:li>immunology</rdf:li>
<rdf:li>antiretroviral therapy</rdf:li>
<rdf:li>hiv-1</rdf:li>
</rdf:Bag>
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Dixit and Perelson's 2nd 2004 mathematical model of viral dynamics in the presence of reverse transcriptase inhibitors.
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