Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil

Aguiar, Bruna Forte; Campos, Guilherme Rodrigues Fernandes; Rodrigues, Josemar; Marques, Nayara Nathiê; Molina, Bárbara Floriano; Bittar, Cíntia; Souza, Fernanda Fernandes; Martinelli, Ana de Lôurdes Candolo; Rahal, Paula; Pereira, Leonardo Régis Leira

doi:10.1016/j.clinre.2019.07.015

Cited by 8 publications

(5 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prevalence of a baseline RAS determined in this study aligns with that reported in other countries 24 - 26 . The NS5A region, as expected, is more susceptible to RAS than the NS5B region, especially in GT1-b, corroborating the conclusions of other studies highlighting that the NS5B region of the HCV genome represents a high barrier to mutations 39 , 40 .…”

Section: Discussionsupporting

confidence: 90%

Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

Santos

Silva

Mendes-Corrêa

et al. 2022

Rev. Inst. Med. trop. S. Paulo

View full text Add to dashboard Cite

The Hepatitis C virus (HCV) infection is a public health problem. The high level of HCV replication and its lack of post-transcriptional correction mechanisms results in the emergence of viral variants and the difficulty in determining polymorphisms and variants that contain the substitutions associated with resistance towards new antivirals. The main focus of this study was to map the NS5A and NS5B polymorphisms and resistance mutations to new antiviral drugs in HCV strains genotype 1 from patients with chronic hepatitis C infection. Serum samples were collected from patients who underwent routine viral load tests at the Instituto Adolfo Lutz, Sao Paulo city, Brazil. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions, respectively, which comprise the HCV genotypes 1a and 1b. The prevalence of resistance mutations found in the NS5A region was 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B-associated RAS was observed for any of the analyzed drugs. These findings support that the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens.

show abstract

Section: Discussionsupporting

confidence: 90%

Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

Santos

Silva

Mendes-Corrêa

et al. 2022

Rev. Inst. Med. trop. S. Paulo

View full text Add to dashboard Cite

show abstract

“…Substitution V1062L was evaluated pan-genotypically (genotypes 1, 2, 3, 4, 5, and unclassified), which is validated by the results of Keiffer et al [51], and Lin et al [50]. V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were found to be genotype 1-specific mutations (Figure 3), which are consistent with reports of Aguiar et al [55], Costa et al [56], and Dietz et al [57]. Additionally, in this study, major NS3 variants that fostered resistance to a particular DAA and/or more than one DAA and NS5A and NS5B resistant variants to a particular DAA were determined, which suggests the possibility of treatment failure.…”

Section: Discussionsupporting

confidence: 88%

Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections

Izhari

2023

Diagnostics

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is a hepatotropic virus that affects millions of human lives worldwide. Direct-acting antiviral (DAA) regimens are the most effective HCV treatment option. However, amino acid substitution-dependent resistance to DAAs has been a major challenge. This study aimed to determine the increasing risk of DAA resistance due to substitutions in DAA target non-structural proteins (NS3/4A, NS5A, and NS5B). Using a Sequence Retrieval System (SRS) at the virus pathogen resource (ViPR/BV-BRC), n = 32763 target protein sequences were retrieved and analyzed for resistance-associated amino acid substitutions (RAASs) by the Sequence Feature Variant Type (SFVT) antiviral-resistance assessment modeling tool. Reference target protein sequences with 100% identity were retried from UniProt following NCBI BLAST. The types and locations of RAASs were identified and visualized by AlphaFold and PyMol. Linux-r-base/R-studio was used for the data presentation. Multi-drug-resistant variants of NS3/4A in genotype 1 (n = 9) and genotype 5 (n = 5) along with DAA-specific NS3/4A, NS5A, and NS5B variants were identified pan-genotypically. A total of 27 variants (RAASs) of all the targets were identified. Fourteen genotype 1-specific substitutions: V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were identified. The most frequent substitutions were V1062L and L2003M, followed by Q2002H. L2003V, Q2002H, M2000T, Y2065N, and NL2003M of NS5A and L2003M of NS5B conferred resistance to daclatasvir. S2702T NS5B was the sofosbuvir-resistant variant. D1194A NS3/4A was triple DAA (simeprevir, faldaprevir, and asunaprevir) resistant. The double-drug resistant variants R1181K (faldaprevir and asunaprevir), A1182V and Q1106K/R (faldaprevir and simeprevir), T1080S (faldaprevir and telaprevir), and single drug-resistant variants V1062L (telaprevir), D1194E/T (simeprevir), D1194G (asunaprevir), S1148A/G (simeprevir), and Q1106L (Boceprevir) of NS3/4A were determined. The molecular phenomenon of DAA resistance is paramount in the development of HCV drug candidates. RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure.

show abstract

“…One patient (# 12) presented RAV Y56F with a high prevalence in both pre-and post-treatment samples. The Y56F is associated with resistance to voxalaprevir and is also associated with disease progression (Vallet et al, 2007), and was frequently reported in Brazilian studies (Aguiar et al, 2020;da Silva et al, 2021). The other patient (# 13), the variant R155 K was found in low frequency (1.9%) that confers resistance to DAAs simeprevir, asunaprevir, boceprevir, grazoprevir, paritaprevir and telaprevir.…”

Section: Discussionmentioning

confidence: 71%

“…observed substitutions in the amino acid positions 168 (D168A/G/T) and 122 (S122G) in a group of few therapy-naïve patients (Andrade et al, 2020). Another study found a variety of RAVs in the NS3 region: S122G/N; G122S/T/N; and I170V in a group of patients infected with HCV-1 (Aguiar et al, 2020).…”

Section: Discussionmentioning

confidence: 95%

Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals

Cabral

Ramos

Silveira

et al. 2022

International Journal of Infectious Diseases

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil

Cited by 8 publications

References 41 publications

Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections

Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals

Contact Info

Product

Resources

About