MONDAY JUNE 12, 2006

SIMULATIONS OF HIV INFECTION

This is a joint work with Fabrizio Poccia, Gianpiero D'Offizi (Internationalal Center for AIDS and other Emerging Infections, Institute for Infectious Diseases (IRCCS)) and Massimo Bernaschi (IAC - CNR)

We implemented a discrete (Cellular Automata or Agent-Based) simulator of the cellular and humoral immune response to the HIV-1 infection. We study the dynamics of the HIV-1 diversity and divergence from the wild-type as an adaptive walk in a bit-string space. Statistical analysis of a set of simulations indicates that the model we employ is able to confirm a number of experimental and clinical findings about the progression to the immunodeficiency syndrome. We found that HIV-1 accumulates bit-mutations mainly in the peptide due to the cytotoxic activity of the CD8 T cells. The viral load appears to be very closely correlated with the time from the infection to AIDS for the short-term progressors than for normal or long-term progressors. Impairment of the CD4 repertoire, while not directly correlated with the onset of AIDS, determines the final outbreak of an opportunistic disease. Simulations do not disagree with the viral-diversity-threshold hypothesis. Realistic correlations between CD4, CD8 counts and viral load is found. Statistics computed over a large number of simulations representing identical initial conditions, are in good agreement with corresponding studies showing a log-normal distribution for the time from infection to AIDS in the real case.

P. Paci, F. Martini, M. Bernaschi, G. D'Offizi and F. Castiglione. Earlier is better: a timely HAART initiation may pave the way for best controllers. BMC Infectious Diseases 11:56 (2011) doi:10.1186/1471-2334-11-56

F. Castiglione and P.Paci. Criticality of timing for anti-HIV therapy initiation. PLoS ONE 5(12): e15294 (2010)

doi:10.1371/journal.pone.0015294

P. Paci, R. Carello, M. Bernaschi, G. D'Offizi and F. Castiglione. Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy. BMC Infectious Diseases. 9: 172 (2009)

doi:10.1186/1471-2334-9-172.

F. Castiglione and M. Bernaschi. HIV-1 strategies of immune evasion. Int J Mod Phys C, 16(12), 1869-1879 (2006)

F. Castiglione, F. Poccia, G. D'Offizi and M. Bernaschi. Mutation, fitness, viral diversity and predictive markers of disease progression in a computational model of HIV-1 infection. AIDS Research and Human Retrovirus 20(12) 1316-1325 (2004)