A model for treatment strategy in the chemotherapy of AIDS.

Mathematical models are developed for the chemotherapy of AIDS. The models are systems of differential equations describing the interaction of the HIV infected immune system with AZT chemotherapy. The models produce the three types of qualitative clinical behavior: an uninfected steady state, an infected steady state (latency) and a progression to AIDS state. The effect of treatment is to perturb the system from progression to AIDS back to latency. Simulation of treatment schedules is provided for the consideration of treatment regimes. The following issues of chemotherapy are addressed: (i) daily frequency of treatment, (ii) early versus late initiation of treatment and (iii) intermittent treatment with intervals of no treatment. The simulations suggest the following properties of AZT chemotherapy: (i) the daily period of treatment does not affect the outcome of the treatment, (ii) treatment should not begin until after the final decline of T cells begins (not until the T cell population falls below approximately 300 mm-3) and then, it should be administered immediately and (iii) a possible strategy for treatment which may cope with side effects and/or resistance, is to treat intermittently with chemotherapy followed by interruptions in the treatment during which either a different drug or no treatment is administered. These properties are revealed in the simulations, as the model equations incorporate AZT chemotherapy as a weakly effective treatment process. We incorporate into the model the fact that AZT treatment does not eliminate HIV, but only restrains its progress. The mathematical model, although greatly simplified as a description of an extremely complex process, offers a means to pose hypotheses concerning treatment protocols, simulate alternative strategies and guide the qualitative understanding of AIDS chemotherapy.