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Talk Abstract
Multi-Phasic HIV Decline During HAART Explained by a CD4 Target/Helper Mathematical Model Implications for AIDS Progression, Immune Reconstitution and Vaccine Development

Avidan U. Neumann and the Comet Study Group
Hopital Pitie-Salpetriere
75012 Paris, France
Department of Life Sciences
Bar-Ilan University
Ramat-Gan 52900, Israel

We show that HIV viral load decline during highly active anti-retroviral therapy (HAART) is multi-phasic, starting with t1/2=0.6 days in first 4 days down to t1/2=80 days after 30 days, rather than bi-phasic as previously reported. This is explainable by a mathematical model that considers the anti-HIV CD4 cells as both target cells and immune helper cells. Reduction in immune activation during therapy has then an important role in HIV kinetics.

The same model also predicts a threshold of target/helper ratio, which explains the rapid progression towards AIDS in some patients and the importance of anti-HIV CD4 cells in long term survivors. In addition, for immune control to be successful, the killing rate of infected cells by the immune system has to be greatly faster than their killing due to the virus according to this model. Based on current estimates for the latter we show that protection from HIV infection by cellular immune response alone is improbable.

Lastly, the result of interruption in HAART is predicted by the model to have a few possible outcomes depending on the changes in the number of CD4 cells as target cells versus as helper cells. We will discuss the various scenarios that can lead to rebound of the viral load back to its steady state before therapy versus control of viral replication by the immune system.

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1998-1999 Mathematics in Biology