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dc.contributor.author
Sede, Mariano Miguel
dc.contributor.author
Laufer, Natalia Lorna
dc.contributor.author
Ojeda, Diego Sebastian
dc.contributor.author
Gun, A.
dc.contributor.author
Cahn, P.
dc.contributor.author
Quarleri, Jorge Fabian
dc.date.available
2015-09-03T16:06:24Z
dc.date.issued
2013-04
dc.identifier.citation
Sede, Mariano Miguel; Laufer, Natalia Lorna; Ojeda, Diego Sebastian; Gun, A.; Cahn, P.; et al.; Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected patients with a null response to nitazoxanide or peg-interferon plus ribavirin; Springer; Archives of Virology; 158; 9; 4-2013; 1001-1008
dc.identifier.issn
0304-8608
dc.identifier.uri
http://hdl.handle.net/11336/1916
dc.description.abstract
Even though new drugs have been approved for HCV treatment, the risk for drug-drug interactions and the concern over overlapping toxicities has hindered the development of studies in HIV/HCV coinfected individuals. Traditional treatment with pegylated interferon plus ribavirin (peg-IFN+RBV) is highly expensive and has low rates of sustained virological response in co-infected patients especially if infected with HCV genotype 1. Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic HCV infection both in HCV monoinfected and HIV/HCV coinfected patients. To understand NTZ resistance mechanism could allow minimizing the development of resistance and expanding the treatment options mainly in special populations such as HIV/HCV coinfected patients. Similarly to IFN, NTZ increases the activity of the cellular protein kinase activated by double-stranded RNA (PKR), a key kinase in the innate antiviral response. In order to elucidate whether sequence heterogeneity in the PKR-binding domain of the HCV genotype 1 NS5A protein could influence the antiviral activity of either NTZ monotherapy or, peg-IFN+RBV, baseline and end-of-therapy plasma samples from two groups of eleven non-responder HIV/HCV coinfected patients that received NTZ or peg-IFN+RBV were studied. Most of the HCV NS5A sequences examined at end-of-therapy did not change from baseline, even after 30 days course of antiviral therapy. An extensive comparison with database HCV-NS5A genotype 1 and 4 sequences with reported IFN therapy outcome was performed in order to infer their phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from therapy non-responder patients were intermingled amongst those the database, irrespective of their IFN-therapy outcome. When comparing the NS5A-PKRBD amino acid identity, it was only significantly different against those sequences ascribed to genotype 4 but not to those of genotype 1 (p<0.0001 and p>0.05, respectively). In conclusion, despite both IFN and NTZ sharing the protein kinase activated by double-stranded RNA as the cellular target, the HCV genotype 1 strategy to counteract the IFN action mediated by NS5A ISDR/PKRBD does not explain drug resistance in HIV/HCV coinfected patients. Other plausible viral factors involved are discussed as well.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Nitazoxanide
dc.subject
Hcv
dc.subject
Genotype 1
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Hiv Coinfection
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
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Farmacología y Farmacia
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected patients with a null response to nitazoxanide or peg-interferon plus ribavirin
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
158
dc.journal.number
9
dc.journal.pagination
1001-1008
dc.journal.pais
Austria
dc.journal.ciudad
Viena
dc.description.fil
Fil: Sede, Mariano Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
dc.description.fil
Fil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos;
dc.description.fil
Fil: Ojeda, Diego Sebastian. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
dc.description.fil
Fil: Gun, A.. Fundación Huésped; Argentina;
dc.description.fil
Fil: Cahn, P.. Fundación Huésped; Argentina; Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos;
dc.description.fil
Fil: Quarleri, Jorge Fabian. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
dc.journal.title
Archives of Virology
dc.relation.isreferencedin
info:eu-repo/semantics/reference es info:eu-repo/semantics/reference/pmid/23553458
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00705-013-1687-6/fulltext.html
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007/s00705-013-1687-6/fulltext.html


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