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Talk abstract

Improving Efficacy of Anti-Viral Chemotherapy - Theory and Experimental Verification

Improving Efficacy of Anti-Viral Chemotherapy - Theory and Experimental Verification

June 7-18, 2004

Tel Aviv University

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.

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