Pharmacodynamics of PEG-IFN-alpha-2a and HCV Response as a Function of IL28B Polymorphism in HIV/HCV-Coinfected Patients
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Citações na Scopus
21
Tipo de produção
article
Data de publicação
2011
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Autores
DAHARI, Harel
COTLER, Scott J.
LAYDEN, Thomas J.
NEUMANN, Avidan U.
Citação
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v.56, n.2, p.95-99, 2011
Resumo
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-coinfected patients from South America. Twenty-six subjects received pegylated interferon 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 IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-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 second slower phase of viral decline (days 2-29) and infected cells loss rate, delta, 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.
Palavras-chave
Mathematical modeling, viral kinetics, pharmacodynamics, HCV, HIV, IL28B, pegylated interferon alpha-2a
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