In my talk I will summarize our work over the last decade, which was aimed at improving the efficacy of anti-HIV chemotherapy. To this end we defined a simple optimization problem whose solution suggested that in chronic HIV treatments a single large AZT daily dosing will be less toxic than the currently used protocol. Recently we have investigated an elaborate optimization problem which enables us to come forward with a consistent, but more subtle, chemotherapy policy. Our murine experiments generally support our theoretical predictions and, in addition, show that 48 hrs following AZT treatment there is a large increase in the lymphoid/erythroid bone-marrow compartment. The possibility that this effect can be manifested in blood T-cells has been ignored in recent mathematical models and clinical experiments, used for evaluating viral and CD4+ cell dynamics in treated patients. In order to investigate it experimentally we applied a long-term, intermittent sub-toxic AZT treatment to virus-free cats. Our results suggest

• a significant AZT damage to the hemopoietic system and, in particular, to CD4+ cells;
• a long-term `memory' of AZT damage;
• exhaustion of the lymphocyte re-population capacity due to chronic AZT treatment.

1. Agur Z., Biomedical modelling and Simulation, ed. Eisenfeld et al., (JC Baltzer AG, Scientific Publ. Co. 59, 1988).
2. Agur Z., Lancet 334 (ii), (1989), pp. 737.
3. Agur Z, Arnon R. Sandak B. and Schechter B., Exp. Hematol. 19 (1991) pp. 364.
4. Cojocaru L. and Agur Math. Biosci. 109 (1992) pp. 531.
5. Agur Z. Cojocaru L. et al., JBS. 3 (1995) pp. 241.
6. Kestel A. Danon YL et al., (Submitted).
7. Levy S. Hassin R. and Agur Z (In preparation).

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1998-1999 Mathematics in Biology