Pharmacodynamics of PEG-IFN alpha-2a and HCV response as a function of IL28B polymorphism in HIV/HCV co-infected patients
journal contributionposted on 08.11.2013 by Evaldo Stanislau Affonso de Araújo, Harel Dahari, Scott J. Cotler, Thomas J. Layden, Avidan U. Neumann, Carlos Eduardo Melo, Antonio Alci Barone
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We examined the association between IL28B single‐nucleotide‐polymorphism rs12979860, hepatitis C virus (HCV) kinetic and pegylated‐interferon‐alpha‐2a pharmacodynamic parameters in HIV/HCV‐co‐infected patients from South America. Twenty‐six subjects received PEG‐IFN‐alpha‐2a+ribavirin. Serum HCV‐RNA and interferon concentrations were measured frequently during the first 12‐weeks of therapy and analyzed using mathematical models. African Americans and Whites had a similar distribution of IL28B genotypes (p=0.5). The CC genotype was overrepresented (p=0.015) in patients infected with HCV genotype-3 compared to genotype-1. In both genotype-1 and genotype-3, the first‐phase‐viral decline and the average PEG‐IFNalpha‐ 2a effectiveness during the first week of therapy were larger (trend P≤0.12) in genotype‐CC compared with genotypes‐TC/TT. In genotype‐1 patients, the secondslower phase of viral decline (days 2‐29) and infected‐cells‐loss rate, , were larger (p=0.02 and 0.11, respectively) in genotype‐CC than in genotypes‐TC/TT. These associations were not observed in genotype‐3 patients.