_^^^^^ Mathematical modeling combined with experiment has led to increased understanding of the processes that underlie HIV-1 infection the development of improved therapies. Nevertheless HIV has not eradicated from infected individuals. Here we propose to develop more realistic models of HIV infection and treatment that include coreceptor usage and effects of CCR5 blocking drugs. We will also analyze the dynamics of SIV and T cell populations in SIV infections in their natural hosts, which are nonpathogenic, in order to better understand the nature of HIV pathogenesis. Infection by hepatitis C virus (HCV) and hepatitis B virus (HBV) continue to cause liver failure and hepatocellular carcinoma in infected individuals. Understanding the basis of pathogenesis and the development of potent antiviral therapies for these viruses lag behind our advances in HIV. We propose to expand our efforts in modeling HCV and HBV in vivo kinetics and the effects of antiviral therapy. In the case of HCV we propose to develop realistic models of new treatments using ribavirin, pegylated interferon a2b, protease and polymerase inhibitors, as well as to understand the effects on infection on CD4+ and CD8+ T cell kinetics. For HBV we propose to both develop new dynamic models of infection as well as to examine with modeling the effectiveness of therapies involving combinations of antiviral agents. Our goal in all of these analyses is to gain basic understanding and help move that understanding into new treatments.
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