This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The proposed research will investigate the hypothesis that pre-treatment sequence variation of NS5A region and the decrease in diversity of Hepatitis C Virus (HCV) quasispecies over time is associated with a faster 1st phase decline in viral titer during interferon (IFN) therapy. To test this hypothesis, we have proposed the following specific aims: 1. Define the 1st and 2nd phase viral decay in patient populations known to have lower responses to HCV therapy. We will compare HCV kinetics of African Americans to Caucasians as well as HIV/HCV to HCV. Patients will be equally distributed between African Americans and Caucasians infected with HCV genotype 1 alone or with concurrent HIV infection. Patients will be treated with pegylated IFN and ribavirin (RBV), as standard of care. Viral decay kinetic analysis will be used to further define whether there is a relationship between early responses to therapy and race or HIV status. 2. Determine the relationship of HCV sequence diversity in the NS5A -coding region with the early phase viral decay and the outcome of IFN therapy. Using the samples derived in Specific Aim 1, we will examine the temporal dynamics of HCV-NS5A sequence complexity and diversity during the 1st phase of interferon therapy.
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