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Gene therapy of T helper cells in HIV infection: Mathematical model of the criteria for clinical effect

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Abstract

The paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction of cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.

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  1. Laboratory for Infectious Diseases, Hyidovre Hospital, University of Copenhagen, DK-2650, Hvidovre, Denmark

    Ole Lund, Ole Søgaard Lund, Gregers Gram, Susanne Dam Nielsen, Kristian Schønning, Jens Ole Nielsen & John-Erik Stig Hansen

  2. Department of Physics, Technical University of Denmark, DK-2800, Lyngby, Denmark

    Erik Mosekilde

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Lund, O., Lund, O.S., Gram, G. et al. Gene therapy of T helper cells in HIV infection: Mathematical model of the criteria for clinical effect. Bltn Mathcal Biology 59, 725–745 (1997). https://doi.org/10.1007/BF02458427

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