uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden
Vise andre og tillknytning
2015 (engelsk)Inngår i: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 47, nr 8, s. 555-562Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naive patients and such baseline resistance will potentially complicate future treatment strategies. Methods: A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naive patients of HCV genotypes 1a, 1b, 2b and 3a. Results: The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Conclusion: Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

sted, utgiver, år, opplag, sider
2015. Vol. 47, nr 8, s. 555-562
Emneord [en]
Hepatitis C virus, NS5A, prevalence, polymorphism, baseline resistance
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-259636DOI: 10.3109/23744235.2015.1028097ISI: 000357738200007PubMedID: 25851241OAI: oai:DiVA.org:uu-259636DiVA, id: diva2:847747
Merknad

Funding: Uppsala-Orebro Regional Research Council, Selander Foundation

Tilgjengelig fra: 2015-08-21 Laget: 2015-08-10 Sist oppdatert: 2016-01-07bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Lannergard, Anders

Søk i DiVA

Av forfatter/redaktør
Lannergard, Anders
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 350 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf