Model-based analysis of inhibition phenomena: immunological tolerance and HIV infection

Although HIV is cytopathogenic for CD4⁺ lymphocytes in vitro, the depletion of these cells in HIV-infected individuals seems to be caused by some other mechanism. The mathematical model of immunological tolerance was used for simulation of CD4⁺ lymphocyte depletion dynamics in HIV infection under the assumption that it is caused by HIV products. This model was unable to simulate the observed three-stage dynamics of CD4⁺ cell counts. When an immune reaction limiting HIV reproduction was included in the model, all these three phases of CD4⁺ lymphocyte depletion could be simulated. In the paper, different modifications and extensions of the model are reviewed and compared with available clinical data, and their relevance for HIV research is discussed together with its suitability to analyze various treatment schemes including chemotherapy and immunotherapy