Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K

Martínez, Alfredo P.; Culasso, Andrés Carlos Alberto; Pérez, Paula Soledad; Romano, Vanesa; Campos, Rodolfo Héctor; Ridruejo, Ezequiel; García, Gabriel; Lello, Federico A. Di

doi:10.1016/j.virusres.2017.08.006

Cited by 7 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, no association between the presence of RASs in any region and the outcome of IFN‐free treatment was found; this result comes from the 22 treated patients who presented baseline RASs determinations in NS5A and NS5B. The only HCV‐1a infected patient treated with EBR/GZV who relapsed had a substitution in NS5A (H58L) but no mutations were observed in NS3, as analyzed in a previous study . Although it is an isolated case, this RAS should be taken into consideration.…”

Section: Discussioncontrasting

confidence: 40%

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Martínez

García

Ridruejo

et al. 2019

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

Direct acting antiviral (DAA) therapy against hepatitis C virus (HCV) increases sustained virologic response rates. Nevertheless, drug resistance has occasionally been associated with failure to DAA. However, the information about the prevalence of NS5A and NS5B resistance-associated substitutions (RASs) in Argentina is very scarce. In this study, we determine the prevalence of NS5A and NS5B resistances to treatment in Argentinean DAA treatment-naïve patients chronically infected with genotype 1 (HCV-1). In this retrospective cross-sectional study, 108 HCV-1-infected patients were studied. RASs in NS5A and NS5B were analyzed by Sanger at baseline and phylogenetic analysis was performed. NS5A and NS5B RASs were detected in 25.8% and 6.3% of the analyzed sequences, respectively. The most frequent primary RASs for NS5A were L31M (7.5%) and Y93H (3.2%) and for NS5B was L159F (3.8%). No association between the presence of RASs and the outcome of DAA treatment was found in this study. Additionally, most of the Argentinean samples were randomly distributed among sequences around the world in the phylogenetic analysis. Only one significant Argentinean cluster was observed in both regions but without any particular RASs pattern. Baseline RASs in NS5A and NS5B were frequently observed in HCV-1-infected patients from Buenos Aires, Argentina but not related to treatment outcome. No clusters related to RASs transmission were observed in the phylogenetic analysis. The frequency of RASs detected in this study supports the need for more molecular epidemiology studies on RASs to adjust local treatment guidelines with the incorporation of autochthonous data. K E Y W O R D Sdirect-acting antiviral, hepatitis C virus, molecular epidemiology, therapy

show abstract

Section: Discussioncontrasting

confidence: 40%

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Martínez

García

Ridruejo

et al. 2019

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite the availability of DAAs drugs for the treatment of HCV, natural mutation still remains a big challenge (Vermehren and Sarrazin, 2011;Paolucci et al, 2013;Martinez et al, 2017). The rate of PIs natural mutations reported being wide to conclude for all areas Genotype Variations 1a and 1b(N=5) S7A(3), Q9R, T10W, R11F, Q28R, V48I(2), V51A, K62R, A66G(3), P67A, T72N, P86Q/A(3), K87A(3), Q89P, R117C, V132I(2), F147S/A(4), A150V, I153L, V170I(3), N174S(2) 3a(N=9) T16A , N27D , T30A , S37Y , A39T(3), I52M(9), A67V(3), P89S , A98T(6), S102A(9), V107I , L132I(2), A133S, A151V, S166A(8), V170I(8), T177S , A179T Table 2.…”

Section: Discussionmentioning

confidence: 99%

“…The Substitutions and Their Frequency in Sample Sequences. The more prevalent substitutions were indicated by underline marker and PIs resistance mutations were bolded and genotypes (Vallet et al, 2005;Lopez-Labrador et al, 2008;Paolucci et al, 2012;Martinez et al, 2017;Morsica et al, 2017). Although there are a couple of reports regarding this issue around the world, in Iran limited publications have considered it.…”

Section: Discussionmentioning

confidence: 99%

“…Although there are a couple of reports regarding this issue around the world, in Iran limited publications have considered it. Actually, the impact of some PIs resistance on HCV DAAs treatment should be considered as their occurrence before the starting of therapy may render resistance even when being treated with other DAAs (Paolucci et al, 2012;Lamb, 2017;Martinez et al, 2017;Morsica et al, 2017). Herein, NS3 protease sequence of a small patient population that determined as non-responder to Peg-IFN plus Ribavirin treatment were analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…The natural and pre-existing drug resistance substitutions in the protease region have been reported in a couple of reports (Bartels et al, 2008;Paolucci et al, 2012;Vicenti et al, 2012;Zeminian et al, 2013;Jindal et al, 2017). There are different well-defined substitutions alongside the protease region that are responsible for PIs resistant, including V36L, T54S, V55A, Q80H, R155K, A156S and V170A and V36M which may affect the therapy response (Vallet et al, 2011;Jindal et al, 2017;Martinez et al, 2017).…”

Section: Research Articlementioning

confidence: 99%

See 2 more Smart Citations

The Investigation of Drug Resistance Substitutions in NS3 Protease Sequence of Hepatitis C Virus from Non-Responder Patients

Nejabat

Hosseini

Sarvari

et al. 2019

Asian Pac J Cancer Prev

View full text Add to dashboard Cite

Background:Even with the fantastic successes of direct-acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) infection, natural drug resistance remains a challenging obstacle for their impacts. The data regarding protease inhibitors (PIs) resistance in Iran population are limited. The aim of this study was to investigate the variations in NS3 protease of HCV from non-responder patients.Methods:In this cross-sectional study, 14 HCV infected patients with genotype 1(N=5) and 3(N=9) who have not responded to Interferon-related regime were enrolled from Liver Clinic, Shiraz. The NS3 protease region was amplified by Nested-PCR followed by product gel extraction. Besides, some amplified protease regions were cloned into a cloning vector to improve the sensitivity of mutation detection. Both crude and cloned sequences were then introduced into sequencing. The obtained sequences were compared with the NS3 reference sequences and analyzed by Geno2pheno available software to find possible substitutions. In the end, the phylogenetic tree was constructed. Results:Among variations responsible for PIs resistance, only one out of 14 (7%) sample who was infected with genotype 1a, harbored R117C+N174S double mutation, which causes reduced susceptibility to Telaprevir. Any another resistance mutation was not found among the studied population. The most frequent substitutions were determined as I52M(N=9), S102A(N=9), S166A(8) and V170I(8) for genotype 3a, and F147S/A(4) for genotype 1. However, some uncharacterized substitutions on scored position, including I132L(N=1), I170V(N=3) and N174S(N=2) were also determined among sequences. Phylogenetic analysis demonstrated that the protease region has enough power to correctly classify enrolled samples into relevant clusters on the tree. There were 2, 3 and 9 cases of sub-genotypes 1a, 1b, and 3a, respectively.Conclusion:A low frequency of PIs resistance mutations in our HCV infected population is a hopeful point of starting these drugs in HCV infected patients.

show abstract

World-wide Prevalence of Substitutions in HCV Genome Associated With Resistance to Direct-Acting Antiviral Agents

Liu

Mao

et al. 2021

Clinical Gastroenterology and Hepatology

View full text Add to dashboard Cite

Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K

Cited by 7 publications

References 50 publications

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

The Investigation of Drug Resistance Substitutions in NS3 Protease Sequence of Hepatitis C Virus from Non-Responder Patients

World-wide Prevalence of Substitutions in HCV Genome Associated With Resistance to Direct-Acting Antiviral Agents

Contact Info

Product

Resources

About