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Prevalence and Factors Related to Natural Resistance-Associated Substitutions to Direct-Acting Antivirals in Patients with Genotype 1 Hepatitis C Virus Infection

1
Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), CONICET, Instituto Universitario del Hospital Italiano (IUHI), Hospital Italiano (HIBA), C1199ACL Buenos Aires, Argentina
2
Sección de Hepatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires, C1199ABB Buenos Aires, Argentina
3
Departamento de Investigación, Hospital Italiano de Buenos Aires, C1199ABB Buenos Aires, Argentina
4
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina
5
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1425FQB Buenos Aires, Argentina
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(1), 3; https://doi.org/10.3390/v11010003
Received: 26 October 2018 / Revised: 14 December 2018 / Accepted: 19 December 2018 / Published: 21 December 2018
(This article belongs to the Section Antivirals & Vaccines)
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PDF [291 KB, uploaded 21 December 2018]

Abstract

This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide. View Full-Text
Keywords: hepatitis C virus; resistance-associated substitutions; direct-acting antivirals; quasispecies hepatitis C virus; resistance-associated substitutions; direct-acting antivirals; quasispecies
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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MDPI and ACS Style

Esposito, I.; Marciano, S.; Haddad, L.; Galdame, O.; Franco, A.; Gadano, A.; Flichman, D.; Trinks, J. Prevalence and Factors Related to Natural Resistance-Associated Substitutions to Direct-Acting Antivirals in Patients with Genotype 1 Hepatitis C Virus Infection. Viruses 2019, 11, 3.

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