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. It is probably a direct destructive or inhibitory effect of the viral products or an (auto)immune reaction elicited by them, eventually directed at them. 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 not able to simulate the observed three-stage dynamics of CD4+ cell counts, i.e., drop of these counts around seroconversion, followed by a slow decrease over a prolonged period and an accelerated decrease before the development of AIDS. 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, compared with available clinical data, and their relevance for HIV research is discussed.
Mathematical modelling of the transmission dynamics of HIV infection and AIDS: a review