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Modeling Plasma Virus Concentration and CD4+ T Cell Kinetics during Primary HIV Infection

Listed author(s):
  • Max A. Stafford
  • Yunzhen Cao
  • David D. Ho
  • Lawrence Corey
  • Crystal L. Mackall
  • Ronald E. Gress
  • Alan S. Perelson
Registered author(s):

    During primary HIV infection the viral load in plasma increases, reaches a peak, and then declines. Phillips has suggested that the decline is due to a limitation in the number of cells susceptible to HIV infection, while other authors have suggested that the decline in viremia is due to an immune response. Here we address this issue by developing models of primary HIV-1 infection, which include T cell kinetics, and by comparing predictions from these models with data from nine, anti-retroviral drug-naive infected patients. Applying nonlinear least squares estimation, we find that relatively small variations in parameters are capable of mimicking the highly diverse patterns found in patient viral load data. This approach yields an estimate of two days for the lifespan of productively infected cells during primary infection, a value that is consistent with results obtained by drug perturbation experiments. We find that all patient data sets considered are consistent with a target-cell limited model from the time of initial infection until shortly after the peak in viremia, but some data sets are not consistent after the peak value with the assumptions of such a model. We illustrate that two possible immune response mechanisms, cytotoxic T lymphocyte destruction of infected target cells and cytokine suppression of viral replication, could account for declines in viral load data not predicted by the original target-cell limited model. We conclude that some additional process, perhaps mediated by CD8+ T cells, is important in at least some patients. Submitted to J. Theor. Biol.

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    Paper provided by Santa Fe Institute in its series Working Papers with number 99-05-036.

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    Date of creation: May 1999
    Handle: RePEc:wop:safiwp:99-05-036
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    1. Ashley T. Haase & Keith Henry & Mary Zupancic & Gerlad Sedgewick & Russell A. Faust & Holly Melroe & Winston Cavert & Kristin Gebhard & Katherine Staskus & Zhi-Qiang Zhang & Peter J. Dailey & Henry H., 1996. "Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue," Working Papers 96-07-045, Santa Fe Institute.
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