Optimization by Simulated Annealing of Structured Therapeutic Interruptions for Highly Active Anti Retroviral Therapy

Highly Active Anti Retroviral Therapies(HAART) are currently the only therapies for treatment of HIV infections. Even if HAART cannot completely clear the infection, it extends the life expectancy of HIV positive individuals, often leading HIV almost to the state of a cronical disease. Unfortunately such therapies have several issues including the emergence of drug resistant mutants and side effects of the drugs that force therapy interruption. For this reason many attempts have been taken in finding a suitable schedule of Structured Therapeutic Interuptions (STI) to suspend therapy without losing too much of the treatment protection. Early experiments on human seemed to yield good results on the short term but recent studies showed to a negative effect of STI on the long term. Although the use of STI is still very controversial, tests on humans have slowed down because of the high risks.
Given this situation, a computational model to investigate the effect of STI on the infection dynamics seems extremely useful. We describe an application of Simulated Annealing algorithm (SA) aiming at finding the optimal schedule for a HAART simulated with the C-ImmSim, an agent based model (ABM) of the immune system. C-ImmSim features the most significant entities and molecular mechanisms of the immune system, reproducing the immune response of several virtual patients to the HIV-1 infection. In this colloquium we'll introduce the C-ImmSim and discuss the simulated annealing algorithm designed to search for the optimal STI that maximizes immune restoration and minimizes both the viral load and the dose of drugs administered to the virtual patient.