Location: Nelson, Murray, Perelson, 2000 @ 039700a89cc6 / nelson_murray_perelson_2000_delay.cellml

Author:
Tessa Paris <tpar054@aucklanduni.ac.nz>
Date:
2010-02-19 14:53:24+13:00
Desc:
Split the model into the general and delay versions. Neither recreate the figure in the paper
Permanent Source URI:
http://models.cellml.org/workspace/nelson_murray_perelson_2000/rawfile/039700a89cc6491d6495f1f1fa790e5783838b3f/nelson_murray_perelson_2000_delay.cellml

<?xml version="1.0" encoding="utf-8"?>
<!--
This CellML file was generated on 12/02/2010 at 2:20:07 at p.m. using:

COR (0.9.31.1333)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk

CellML 1.0 was used to generate this model
http://www.cellml.org/
-->
<model 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:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" name="nelson_murray_perelson_2000_version01" cmeta:id="nelson_murray_perelson_2000_version01" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
	<documentation xmlns="http://cellml.org/tmp-documentation">
		<article>
			<articleinfo>
				<title>A Model of HIV-1 Pathogenesis</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 the delay model from the paper. It runs in COR and OpenCell but it does not replicate the figures in the paper. The parameter 'm' is not known.
          </para>
			</section>
			<sect1 id="sec_structure">
				<title>Model Structure</title>
				<para>
				ABSTRACT:
				</para>
				<para>
Mathematical modeling combined with experimental measurements have yielded important insights into HIV-1 pathogenesis. For example, data from experiments in which HIV-infected patients are given potent antiretroviral drugs that perturb the infection process have been used to estimate kinetic parameters underlying HIV infection. Many of the models used to analyze data have assumed drug treatments to be completely efficacious and that upon infection a cell instantly begins producing virus. We consider a model that allows for less then perfect drug effects and which includes a delay in the initiation of virus production. We present detailed analysis of this delay differential equation model and compare the results to a model without delay. Our analysis shows that when drug efficacy is less than 100%, as may be the case in vivo, the predicted rate of decline in plasma virus concentration depends on three factors: the death rate of virus producing cells, the efficacy of therapy, and the length of the delay. Thus, previous estimates of infected cell loss rates can be improved upon by considering more realistic models of viral infection..
				</para>
				<para>
The complete original paper reference is cited below:
</para>
				<para>
A model of HIV-1 pathogenesis that includes an intracellular delay, Patrick W. Nelson, James D. Murray, and Alan S. Perelson, 2000, <emphasis>Mathematical Biosciences</emphasis>, 163, 201-215.  <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/10701304?dopt=Abstract">PubMed ID: 10701304</ulink>
				</para>
				<informalfigure float="0" id="fig_reaction_diagram">
					<mediaobject>
						<imageobject>
							<objectinfo>
								<title>reaction schematic for the model</title>
							</objectinfo>
							<imagedata fileref="nelson_2000.png"/>
						</imageobject>
					</mediaobject>
					<caption>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.</caption>
				</informalfigure>
			</sect1>
		</article>
	</documentation>
	<rdf:RDF>
		<rdf:Bag rdf:about="rdf:#749d1119-0fcc-4a2a-8adc-9827b7083403">
			<rdf:li>viral dynamics</rdf:li>
			<rdf:li>hiv-1</rdf:li>
			<rdf:li>immunology</rdf:li>
		</rdf:Bag>
		<rdf:Seq rdf:about="rdf:#7a8ec4ac-cc9d-4ecd-84ee-55e4fb2aa8f9">
			<rdf:li rdf:resource="rdf:#f30f8234-9eff-4782-bc29-66b4ff442f15"/>
			<rdf:li rdf:resource="rdf:#2e7a36f4-a80f-4484-a183-7425f2f1499c"/>
			<rdf:li rdf:resource="rdf:#a69705df-52c6-462b-9ceb-8bfc2bd5fa28"/>
		</rdf:Seq>
		<rdf:Description rdf:about="">
			<dc:publisher>
        The University of Auckland, Bioengineering Institute
      </dc:publisher>
			<cmeta:modification xmlns:cmeta="http://www.cellml.org/metadata/1.0#" rdf:resource="rdf:#3978135f-92f8-4c74-96eb-9dcd1f89376e"/>
			<cmeta:modification xmlns:cmeta="http://www.cellml.org/metadata/1.0#" rdf:resource="rdf:#95b7541c-7fd8-4e18-b69c-6a4735f7f9cc"/>
			<dcterms:created rdf:resource="rdf:#cac9fbaf-82e3-41b6-8980-f9b08394ef2c"/>
			<dc:creator rdf:resource="rdf:#3a47a9ff-8d86-4581-8cba-71fda376c533"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#1f1f7b30-757a-41be-b35c-ce6b8845c877">
			<dc:subject rdf:resource="rdf:#6ccc5777-1271-4a22-9ddb-47c190828b6b"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#4b2ad750-50dc-46d4-a1ff-48c8504c61c8">
			<dc:creator rdf:resource="rdf:#27decb27-3604-43a1-9806-b21f55e45817"/>
			<rdf:value>
          This is the CellML description of Nelson et al's 2000 mathematical 
          model of HIV-1 pathogenesis.
        </rdf:value>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#2e7a36f4-a80f-4484-a183-7425f2f1499c">
			<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
			<vCard:N rdf:resource="rdf:#32879fab-cd44-48bd-bc7a-2a3747b8fe0d"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#672024df-27d6-4e66-a6fc-d1efc2588114">
			<vCard:Given>Autumn</vCard:Given>
			<vCard:Family>Cuellar</vCard:Family>
			<vCard:Other>A</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#b11da091-0bb0-4fd0-ad1c-8545ef3926fb">
			<vCard:Given>Peter</vCard:Given>
			<vCard:Family>Villiger</vCard:Family>
			<vCard:Other>J</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#0b8595b9-aa60-46c1-b809-ac351938d98c">
			<dcterms:W3CDTF>2000-02</dcterms:W3CDTF>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#1718289f-4a02-443a-804d-35c1ed924d4e">
			<vCard:Given>Catherine</vCard:Given>
			<vCard:Family>Lloyd</vCard:Family>
			<vCard:Other>May</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#6ccc5777-1271-4a22-9ddb-47c190828b6b">
			<bqs:subject_type>keyword</bqs:subject_type>
			<rdf:value rdf:resource="rdf:#749d1119-0fcc-4a2a-8adc-9827b7083403"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#32879fab-cd44-48bd-bc7a-2a3747b8fe0d">
			<vCard:Given>James</vCard:Given>
			<vCard:Family>Murray</vCard:Family>
			<vCard:Other>D</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#64d552c3-b1e2-4259-b7c4-094d3783c255">
			<bqs:Pubmed_id>10701304</bqs:Pubmed_id>
			<bqs:JournalArticle rdf:resource="rdf:#3a98986f-83c2-414e-b931-2f71f65dec02"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#3978135f-92f8-4c74-96eb-9dcd1f89376e">
			<dcterms:modified rdf:resource="rdf:#b9f4b57a-2a32-4cbd-8f9d-4724e72923db"/>
			<rdf:value>
          Added publication date information.
        </rdf:value>
			<cmeta:modifier xmlns:cmeta="http://www.cellml.org/metadata/1.0#" rdf:resource="rdf:#e050cd59-4eaa-4585-8d49-d786993f42a0"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#23464419-faba-4253-85ab-8dff106712d0">
			<vCard:Given>Patrick</vCard:Given>
			<vCard:Family>Nelson</vCard:Family>
			<vCard:Other>W</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#83ae3667-b517-47f5-9a98-9c10807851c4">
			<vCard:Orgname>The University of Auckland</vCard:Orgname>
			<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#3a47a9ff-8d86-4581-8cba-71fda376c533">
			<vCard:ORG rdf:resource="rdf:#83ae3667-b517-47f5-9a98-9c10807851c4"/>
			<vCard:EMAIL rdf:resource="rdf:#5a476bfe-899a-439d-bf2f-067d0befc3ff"/>
			<vCard:N rdf:resource="rdf:#1718289f-4a02-443a-804d-35c1ed924d4e"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#b9f4b57a-2a32-4cbd-8f9d-4724e72923db">
			<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#5a476bfe-899a-439d-bf2f-067d0befc3ff">
			<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
			<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
		</rdf:Description>
		<rdf:Description rdf:about="#nelson_murray_perelson_2000_version01">
			<dc:title>
         Nelson et al's 2000 mathematical model of HIV-1 pathogenesis.
      </dc:title>
			<cmeta:bio_entity xmlns:cmeta="http://www.cellml.org/metadata/1.0#">T-cells</cmeta:bio_entity>
			<cmeta:comment xmlns:cmeta="http://www.cellml.org/metadata/1.0#" rdf:resource="rdf:#4b2ad750-50dc-46d4-a1ff-48c8504c61c8"/>
			<bqs:reference rdf:resource="rdf:#1f1f7b30-757a-41be-b35c-ce6b8845c877"/>
			<bqs:reference rdf:resource="rdf:#64d552c3-b1e2-4259-b7c4-094d3783c255"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#e050cd59-4eaa-4585-8d49-d786993f42a0">
			<vCard:N rdf:resource="rdf:#672024df-27d6-4e66-a6fc-d1efc2588114"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#3a98986f-83c2-414e-b931-2f71f65dec02">
			<dc:creator rdf:resource="rdf:#7a8ec4ac-cc9d-4ecd-84ee-55e4fb2aa8f9"/>
			<dc:title>
            A model of HIV-1 pathogenesis that includes an intracellular delay
          </dc:title>
			<bqs:volume>163</bqs:volume>
			<bqs:first_page>201</bqs:first_page>
			<bqs:Journal rdf:resource="rdf:#48d11cbb-9218-4869-a5bd-ac549a7c1c0b"/>
			<dcterms:issued rdf:resource="rdf:#0b8595b9-aa60-46c1-b809-ac351938d98c"/>
			<bqs:last_page>215</bqs:last_page>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#a69705df-52c6-462b-9ceb-8bfc2bd5fa28">
			<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
			<vCard:N rdf:resource="rdf:#60e0c060-b4f4-4621-924e-2c14cba0d784"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#cac9fbaf-82e3-41b6-8980-f9b08394ef2c">
			<dcterms:W3CDTF>2002-12-05</dcterms:W3CDTF>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#f30f4744-c1b1-4397-b619-3af752f22d97">
			<vCard:N rdf:resource="rdf:#b11da091-0bb0-4fd0-ad1c-8545ef3926fb"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#95b7541c-7fd8-4e18-b69c-6a4735f7f9cc">
			<dcterms:modified rdf:resource="rdf:#315aca85-981c-45b0-bb40-c9483d37ff1d"/>
			<rdf:value>
          Corrected syntax error with base_units
        </rdf:value>
			<cmeta:modifier xmlns:cmeta="http://www.cellml.org/metadata/1.0#" rdf:resource="rdf:#f30f4744-c1b1-4397-b619-3af752f22d97"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#48d11cbb-9218-4869-a5bd-ac549a7c1c0b">
			<dc:title>Mathematical Biosciences</dc:title>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#27decb27-3604-43a1-9806-b21f55e45817">
			<vCard:FN>Catherine Lloyd</vCard:FN>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#f30f8234-9eff-4782-bc29-66b4ff442f15">
			<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
			<vCard:N rdf:resource="rdf:#23464419-faba-4253-85ab-8dff106712d0"/>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#60e0c060-b4f4-4621-924e-2c14cba0d784">
			<vCard:Given>Alan</vCard:Given>
			<vCard:Family>Perelson</vCard:Family>
			<vCard:Other>S</vCard:Other>
		</rdf:Description>
		<rdf:Description rdf:about="rdf:#315aca85-981c-45b0-bb40-c9483d37ff1d">
			<dcterms:W3CDTF>2005-04-20</dcterms:W3CDTF>
		</rdf:Description>
	</rdf:RDF>   <units xmlns="http://www.cellml.org/cellml/1.0#" name="day">
      <unit units="second" multiplier="86400"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="per_day">
      <unit units="day" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="ml">
      <unit units="litre" prefix="milli"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="cell" base_units="yes"/>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="viron" base_units="yes"/>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="cells_per_day">
      <unit units="cell"/>
      <unit units="day" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="cells_per_ml">
      <unit units="cell"/>
      <unit units="ml" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="virons_per_day">
      <unit units="viron"/>
      <unit units="day" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="virons_per_cell">
      <unit units="viron"/>
      <unit units="cell" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="virons_per_ml">
      <unit units="viron"/>
      <unit units="ml" exponent="-1"/>
   </units>
   <units xmlns="http://www.cellml.org/cellml/1.0#" name="ml_per_virons_per_day">
      <unit units="ml"/>
      <unit units="viron" exponent="-1"/>
      <unit units="day" exponent="-1"/>
   </units>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="environment">
      <variable name="time" units="day" public_interface="out"/>
      <variable name="tau" units="day" initial_value="1" public_interface="out"/>
      <variable name="lambda" units="cells_per_ml" initial_value="0.005" public_interface="out"/>
      <variable name="delta_1" units="cells_per_day" initial_value="0.03" public_interface="out"/>
      <variable name="delta" units="cells_per_day" initial_value="0.5" public_interface="out"/>
      <variable name="np" units="dimensionless" initial_value="1" public_interface="out"/>
      <variable name="c" units="virons_per_day" initial_value="3" public_interface="out"/>
      <variable name="k" units="ml_per_virons_per_day" initial_value="3.43e-5" public_interface="out"/>
      <variable name="N" units="virons_per_cell" initial_value="480" public_interface="out"/>
      <variable name="m" units="per_day" initial_value="0.000001" public_interface="out"/>
   </component>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="uninfected_T_cells">
      <variable name="T0" units="cells_per_ml" public_interface="out"/>
      <variable name="T" units="cells_per_ml" initial_value="0.0018" public_interface="out"/>
      <variable name="lambda" units="cells_per_ml" public_interface="in"/>
      <variable name="delta" units="cells_per_day" public_interface="in"/>
      <variable name="delta_1" units="cells_per_day" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <variable name="VI" units="virons_per_ml" public_interface="in"/>
      <variable name="k" units="ml_per_virons_per_day" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>T0</ci>
            <cn cellml:units="cells_per_ml">0.0018</cn>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>T</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <ci>lambda</ci>
                     <cn cellml:units="per_day">1</cn>
                  </apply>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <ci>delta_1</ci>
                        <ci>T</ci>
                     </apply>
                     <cn cellml:units="cell">1</cn>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>k</ci>
                  <ci>VI</ci>
                  <ci>T</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="infected_T_cells">
      <variable name="T_in" units="cells_per_ml" initial_value="0.000036" public_interface="out"/>
      <variable name="T0" units="cells_per_ml" public_interface="in"/>
      <variable name="delta" units="cells_per_day" public_interface="in"/>
      <variable name="m" units="per_day" public_interface="in"/>
      <variable name="VI" units="virons_per_ml" public_interface="in"/>
      <variable name="k" units="ml_per_virons_per_day" public_interface="in"/>
      <variable name="tau" units="day" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>T_in</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>k</ci>
                  <ci>T0</ci>
                  <ci>VI</ci>
                  <apply>
                     <minus/>
                     <ci>time</ci>
                     <ci>tau</ci>
                  </apply>
                  <apply>
                     <exp/>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <ci>m</ci>
                        </apply>
                        <ci>tau</ci>
                     </apply>
                  </apply>
                  <cn cellml:units="per_day">1</cn>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <ci>delta</ci>
                     <cn cellml:units="cell">1</cn>
                  </apply>
                  <ci>T_in</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="infectious_virus">
      <variable name="VI" units="virons_per_ml" initial_value="134e3" public_interface="out"/>
      <variable name="delta" units="cells_per_day" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <variable name="N" units="virons_per_cell" public_interface="in"/>
      <variable name="np" units="dimensionless" public_interface="in"/>
      <variable name="c" units="virons_per_day" public_interface="in"/>
      <variable name="T_in" units="cells_per_ml" public_interface="in"/>
      <variable name="log_VI" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>VI</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <apply>
                        <minus/>
                        <cn cellml:units="dimensionless">1</cn>
                        <ci>np</ci>
                     </apply>
                     <ci>N</ci>
                     <ci>delta</ci>
                     <ci>T_in</ci>
                  </apply>
                  <cn cellml:units="cell">1</cn>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <ci>c</ci>
                     <ci>VI</ci>
                  </apply>
                  <cn cellml:units="viron">1</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>log_VI</ci>
            <apply>
               <log/>
               <apply>
                  <divide/>
                  <ci>VI</ci>
                  <cn cellml:units="virons_per_ml">1</cn>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="non_infectious_virus">
      <variable name="VNI" units="virons_per_ml" initial_value="0" public_interface="out"/>
      <variable name="delta" units="cells_per_day" public_interface="in"/>
      <variable name="time" units="day" public_interface="in"/>
      <variable name="N" units="virons_per_cell" public_interface="in"/>
      <variable name="np" units="dimensionless" public_interface="in"/>
      <variable name="c" units="virons_per_day" public_interface="in"/>
      <variable name="T_in" units="cells_per_ml" public_interface="in"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>VNI</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <ci>np</ci>
                     <ci>N</ci>
                     <ci>delta</ci>
                     <ci>T_in</ci>
                  </apply>
                  <cn cellml:units="cell">1</cn>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <ci>c</ci>
                     <ci>VNI</ci>
                  </apply>
                  <cn cellml:units="viron">1</cn>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component xmlns="http://www.cellml.org/cellml/1.0#" name="total_virus">
      <variable name="VNI" units="virons_per_ml" public_interface="in"/>
      <variable name="VI" units="virons_per_ml" public_interface="in"/>
      <variable name="virus_total" units="virons_per_ml"/>
      <variable name="log_virus_total" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>virus_total</ci>
            <apply>
               <plus/>
               <ci>VI</ci>
               <ci>VNI</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>log_virus_total</ci>
            <apply>
               <log/>
               <apply>
                  <divide/>
                  <ci>virus_total</ci>
                  <cn cellml:units="virons_per_ml">1</cn>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <group xmlns="http://www.cellml.org/cellml/1.0#">
      <relationship_ref relationship="containment"/>
      <component_ref component="environment">
         <component_ref component="uninfected_T_cells"/>
         <component_ref component="infected_T_cells"/>
         <component_ref component="infectious_virus"/>
         <component_ref component="non_infectious_virus"/>
         <component_ref component="total_virus"/>
      </component_ref>
   </group>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="uninfected_T_cells" component_2="environment"/>
      <map_variables variable_1="delta" variable_2="delta"/>
      <map_variables variable_1="delta_1" variable_2="delta_1"/>
      <map_variables variable_1="lambda" variable_2="lambda"/>
      <map_variables variable_1="k" variable_2="k"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="infected_T_cells" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="k" variable_2="k"/>
      <map_variables variable_1="delta" variable_2="delta"/>
      <map_variables variable_1="tau" variable_2="tau"/>
      <map_variables variable_1="m" variable_2="m"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="infectious_virus" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="np" variable_2="np"/>
      <map_variables variable_1="N" variable_2="N"/>
      <map_variables variable_1="c" variable_2="c"/>
      <map_variables variable_1="delta" variable_2="delta"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="non_infectious_virus" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="np" variable_2="np"/>
      <map_variables variable_1="N" variable_2="N"/>
      <map_variables variable_1="c" variable_2="c"/>
      <map_variables variable_1="delta" variable_2="delta"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="uninfected_T_cells" component_2="infected_T_cells"/>
      <map_variables variable_1="T0" variable_2="T0"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="infected_T_cells" component_2="infectious_virus"/>
      <map_variables variable_1="T_in" variable_2="T_in"/>
      <map_variables variable_1="VI" variable_2="VI"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="infected_T_cells" component_2="non_infectious_virus"/>
      <map_variables variable_1="T_in" variable_2="T_in"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="uninfected_T_cells" component_2="infectious_virus"/>
      <map_variables variable_1="VI" variable_2="VI"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="total_virus" component_2="non_infectious_virus"/>
      <map_variables variable_1="VNI" variable_2="VNI"/>
   </connection>
   <connection xmlns="http://www.cellml.org/cellml/1.0#">
      <map_components component_1="total_virus" component_2="infectious_virus"/>
      <map_variables variable_1="VI" variable_2="VI"/>
   </connection>
</model>