| Distinct effects of protease and reverse transcriptase inhibition in an immunological model of HIV-1 infection with impulsive drug effects. | |
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MedLine Citation:
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PMID: 15294425 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We present an immunological model that considers the dynamics of CD4+ T cells interacting with free virions, reverse transcriptase inhibiting drugs and protease inhibiting drugs. We divide the T cells into multiple classes and use impulsive differential equations to describe the drug activity. As expected, we find that insufficient dosing of either drug corresponds to high viral load and a large population of infectious T cells. The model further predicts that, in the absence of physiological limits on tolerable drug concentrations, sufficiently frequent dosing with the reverse transcriptase inhibitor alone could theoretically maintain the CD4+ T cell count arbitrarily close to the T cell count in the uninfected immune system. However, for frequent dosing of the protease inhibitor alone, the limiting T cell populations may not be enough to maintain the immune system. Furthermore, frequent dosing of both drugs has the same net effect on the T cell population as frequent dosing of the reverse transcriptase inhibitor only. Thus, the two drug classes can have fundamentally different effects on the long-term dynamics and the reverse transcriptase inhibitor, in particular, plays a crucial role in maintaining the immune system. We also provide estimates for the dosing intervals of each drug that could theoretically sustain the T cell population at a desired level. |
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Authors:
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R J Smith; L M Wahl |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Bulletin of mathematical biology Volume: 66 ISSN: 0092-8240 ISO Abbreviation: Bull. Math. Biol. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-08-05 Completed Date: 2005-06-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0401404 Medline TA: Bull Math Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1259-83 Citation Subset: IM |
Affiliation:
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Department of Applied Mathematics, University of Western Ontario, London, ON, N6A 5B7, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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CD4 Lymphocyte Count CD4-Positive T-Lymphocytes / drug effects, immunology, virology Computer Simulation Drug Therapy, Combination HIV Infections / drug therapy*, immunology* HIV Protease Inhibitors / therapeutic use* HIV-1 / immunology* Humans Models, Immunological* Reverse Transcriptase Inhibitors / therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/HIV Protease Inhibitors; 0/Reverse Transcriptase Inhibitors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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