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Pharmacodynamics of PEG-IFN alpha-2a and HCV response as a function of IL28B polymorphism in HIV/HCV co-infected patients

journal contribution
posted on 08.11.2013, 00:00 authored by Evaldo Stanislau Affonso de Araújo, Harel Dahari, Scott J. Cotler, Thomas J. Layden, Avidan U. Neumann, Carlos Eduardo Melo, Antonio Alci Barone
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.


Grant support: Study carried out with the assistance of Roche Laboratories of Brazil, which provided financial support in the form of the pegylated interferon ‐2a, kits for molecular assays and the shipping of samples. HD is supported by the University of Illinois Walter Payton Liver Center GUILD and by NIH grant P20‐RR018754.


Publisher Statement

This is a copy of an article published in the JAIDS Journal of Acquired Immune Deficiency Syndromes © 2011 Lippincott, Williams & Wilkins DOI: 10.1097/QAI.0b013e3182020596.


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