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.
OBJECTIVE
HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Abbate
Isabella
I
Department of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
Lo Iacono
Oreste
O
Di Stefano
Rosa
R
Cappiello
Giuseppina
G
Girardi
Enrico
E
Longo
Roberta
R
Ferraro
Donatella
D
Antonucci
Giorgio
G
Di Marco
Vito
V
Solmone
Mariacarmela
M
Craxì
Antonio
A
Ippolito
Giuseppe
G
Capobianchi
Maria R
MR
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011092:Polyethylene Glycols; D011379:Prognosis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D014764:Viral Proteins / Q000235:genetics*
D000998:Antiviral Agents; C400562:HVR1 protein, Hepatitis C virus; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014764:Viral Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b