HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substituti...

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Bibliographic Details
Published in:Journal of hepatology 2004-05, Vol.40 (5), p.831-836
Main Authors: Abbate, Isabella, Iacono, Oreste Lo, Di Stefano, Rosa, Cappiello, Giuseppina, Girardi, Enrico, Longo, Roberta, Ferraro, Donatella, Antonucci, Giorgio, Di Marco, Vito, Solmone, Mariacarmela, Craxı̀, Antonio, Ippolito, Giuseppe, Capobianchi, Maria R
Format: Article
Language:English
Subjects:
Adult
Antiviral Agents - administration & dosage
Antiviral Agents - therapeutic use
Biological and medical sciences
Drug Resistance, Viral - genetics
Drug Therapy, Combination
Evolution, Molecular
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genetic Variation
HCV
Hepacivirus - genetics
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - virology
Humans
HVR-1
Interferon
Interferon-alpha - administration & dosage
Interferon-alpha - therapeutic use
Male
Medical sciences
Middle Aged
Phylogeny
Polyethylene Glycols
Prognosis
Quasispecies
Recombinant Proteins
Ribavirin - administration & dosage
Ribavirin - therapeutic use
Viral Proteins - genetics
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Summary:HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy ( T1) and at follow-up ( T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2004.01.019