Document Detail


Genetic heterogeneity of hepatitis C virus (HCV) in clinical strains of HIV positive and HIV negative patients chronically infected with HCV genotype 3a.
MedLine Citation:
PMID:  14518715     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The clinical correlation between the degree of HCV variability and the response to anti-HCV treatment in HIV positive patients infected with HCV genotype 3a is unknown. In this study, 27 HIV positive and 5 HIV negative patients with HCV genotype 3a infection were treated with interferon-alpha-2b with or without ribavirin. Nine patients (5 HIV positive) achieved a sustained virological response (SR) and 23 (only one HIV negative) were non-responders (NR). Sequence analyses of the partial E2 domain and the non-structural 5A protein were performed at baseline in all patients, and before and during treatment in the HIV positive NRs. There was no difference in the mean number of amino acid mutations from HCV 3a prototype, within E2 region, between the HIV positive and HIV negative patients: 17 (range 11-25) vs 16 (range 14-17). The mean baseline number of mutations in E2 region, was similar in HIV positive SRs and NRs: 18 (range 14-25) vs 16 (range 11-19). Phylogenetic analysis of HCV paired serum samples at baseline and during treatment revealed identical E2 sequence in 5/21 HIV positive NR patients, whereas 6 other sequences were strictly related to baseline E2 domain and the remaining 10 were divergent. The mean number of amino acid mutations in the NS5A protein at baseline, was 1 (range 0-3) in HIV negative patients and 2 (range 0-4) in HIV positive ones. This region was highly conserved in all isolates of HIV positive NRs analysed during treatment. These results suggest that genetic variability at baseline within the E2 region and NS5A protein of HCV 3a strain obtained from HIV positive and HIV negative patients is not associated with treatment response. Furthermore, the anti-HCV treatment did not influence HCV heterogeneity within the E2 and NS5A domains in HIV positive patients infected with HCV genotype 3a.
Authors:
S Bagaglio; R Bruno; S Lodrini; M S De Mitri; P Andreone; E Loggi; L Galli; A Lazzarin; G Morsica
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Journal of biological regulators and homeostatic agents     Volume:  17     ISSN:  0393-974X     ISO Abbreviation:  J. Biol. Regul. Homeost. Agents     Publication Date:    2003 Apr-Jun
Date Detail:
Created Date:  2003-10-01     Completed Date:  2004-06-09     Revised Date:  2005-12-23    
Medline Journal Info:
Nlm Unique ID:  8809253     Medline TA:  J Biol Regul Homeost Agents     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  153-61     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, San Raffaele Vita-Salute University, San Raffele Scientific Institute IRCCS, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Alanine Transaminase / blood
Amino Acid Sequence
CD4 Lymphocyte Count
DNA Mutational Analysis / methods
Female
Genetic Heterogeneity*
Genotype
HIV Infections / complications*
Hepacivirus / classification,  drug effects,  genetics*
Hepatitis C / complications,  drug therapy*,  virology
Humans
Interferon Alfa-2b / therapeutic use
Male
Middle Aged
Molecular Sequence Data
Mutation / genetics
Phylogeny
RNA, Viral / blood,  drug effects
Reverse Transcriptase Polymerase Chain Reaction
Ribavirin / therapeutic use
Sequence Alignment
Sequence Homology, Amino Acid
Treatment Outcome
Viral Envelope Proteins / genetics
Viral Load / methods
Viral Nonstructural Proteins / genetics
Viral Proteins / drug effects,  genetics
Chemical
Reg. No./Substance:
0/HVR1 protein, Hepatitis C virus; 0/NS-5 protein, hepatitis C virus; 0/RNA, Viral; 0/Viral Envelope Proteins; 0/Viral Nonstructural Proteins; 0/Viral Proteins; 157184-61-7/glycoprotein E2, Hepatitis C virus; 36791-04-5/Ribavirin; 99210-65-8/Interferon Alfa-2b; EC 2.6.1.2/Alanine Transaminase

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