Modeling the dynamical impact of HIV on the immune system: Viral clearance, infection, and AIDS
A phenomenological model simulating the time-dependent consequences of the HIV challenge on the immune system is presented. One of the important features of the model is its ability to handle T helper cell production and apoptosis (genetically determined suicide). The values of the independent, generally time-dependent, model parameters were chosen to be compatible with known experimental data. A new approach to the numerical solution of the resulting coupled, nonlinear model equations is presented, and simulations of a typical viral challenge that is cleared and one that leads to infection and AIDS are exhibited. It is shown that a change in the saturated value of a single model parameter is sufficient to change a simulated challenge on its way to being cleared into one that leads to infection instead (and vice versa). If the saturated values of all of the independent model parameters are known at the beginning of a challenge, the outcome of the challenge can be predicted in advance. If the virulence of the HIV strain (defined in this paper) is above a critical threshold at inoculation, infection will result regardless of the initial viral load. This latter result could explain why accidental HIV contaminated needle sticks sometime result in infection regardless of the counter-measures undertaken. A model simulating the time evolution of the collapse of the T helper cell density leading to AIDS is introduced. This model consists of immunological and mathematical parts and is compatible with experimental data. The immediate cause of the beginning of this collapse is postulated to be a spontaneous mutation of the virus into a more virulent form that not only leads to an explosion in the viral load but also to a dramatic increase in the level of induced apoptosis of T helper cells. The results of this model are consistent with the known experimental behavior of the viral load and T helper cell densities in the final stage of HIV infection. (C) 1999 Elsevier Science Ltd. All rights reserved.
aids apoptosis viral load t helper cell density hiv infection