Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Aguiar, Bruna Forte [1] ; Campos, Guilherme Rodrigues Fernandes [2] ; Rodrigues, Joao Paulo Vilela ; Marques, Nayara Nathie [2] ; Molina, Barbara Floriano [2] ; Bittar, Cintia [2] ; Souza, Fernanda Fernandes [3] ; Martinelli, Ana de Lourdes Candolo [3] ; Rahal, Paula [2] ; Pereira, Leonardo Regis Leira [1]
Total Authors: 10
[1] Univ Sao Paulo, FCFRP USP, Ribeirao Preto Fac Pharmaceut Sci, Cafe Ave, BR-14040903 Ribeirao Preto, SP - Brazil
[2] UNESP Sao Paulo State Univ, Inst Biosci, Dept Biol Language & Exact Sci IBILCE, Cristovao Colombo St 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[3] Univ Sao Paulo, FMRP USP, Ribeirao Preto Sch Med, Bandeirantes Ave 3900, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 1

Background: The World Health Organization estimates that 1% of the world population (71 million) is infected with hepatitis C virus (HCV). In 2015, three direct-acting antivirals (DAAs), simeprevir (SMV), sofosbuvir (SOF) and daclatasvir (DCV) were included in the Brazilian protocol for the treatment of chronic hepatitis C. Despite the fact that the use of these drugs is associated with higher treatment response rates and with lower incidence of side effects, studies have shown the association between the presence of viral resistance mutations and the failure of pharmacological treatment. Aim: This way, this study aimed to evaluate the safety and effectiveness of treatment for HCV genotypes 1a and 1b infected patients with these DAAs, also analyzing the occurrence and prevalence of baseline resistance associated substitutions (RAS), observing the impact of these mutations into the treatment success. Methods: Clinical data were collected from all the 262 HCV infected patients included for comparative analysis, while serum samples collected from 144 of these individuals, before treatment, were submitted to molecular biology approaches for mutation analysis into NS3. NS5A and NS5B regions. Results: Regarding the treatment regimens, 49.6% of the patients received SOF + DCV +/- ribavirin and 50.4% used SOF + SMV +/- ribavirin. The sustained virological response at 12 weeks post-treatment (SVR12) rate was 92.7% (93.9% for SOF plus DCV and 91.7% for SOF plus SMV). No clinical or laboratorial factor was statistically associated with SVR. The most common adverse reactions were haematological events, nausea/vomiting, headache and asthenia. Out of 144 blood samples, 70 (48.6%) had detected RAS, 34.8% treated with SOF + DCV +/- ribavirin and 61.3% SOF + SMV +/- ribavirin. The resistance mutations against SMV were detected into NS3: substitutions G122S (28%), I170V (22.7%), Y56F (17.3%) and V1321 (14.7%). The mutations against DCV R30Q (9.1%), P58H (6.1%) and Q62E (6.1%) were observed into NS5A, and for SOF the mutations A421V (10.6%), L159F (6.4%) and C316N (6.4%) were present inside NS5B viral protein. Four patients did not reach SVR, three of them presented viruses carrying RAS (1 treated with SOF + DCV and 2 with SOF+ SMV). Some of these mutations, like R30Q (present in relapsing samples) and L159F, are well known by their influence on antiviral resistance, while others, like C316N, have a compensatory effect on viral fitness, maintaining these baseline RAS. Conclusion: The use of treatment regimens composed of SOF and DCV or SOF and SMV showed a high SVR rate, despite of a high rate of RAS, and a good tolerability profile in patients with HCV genotype 1. However, the high occurrence of baseline RAS observed in this casuistic is still a concern and studies like this show the necessity to understand how they are maintained in the population and to direct more efficiently the use of DAAs. (C) 2019 Elsevier Masson SAS. All rights reserved. (AU)

FAPESP's process: 18/05974-7 - Survey of the frequency of resistance mutations to direct acting antivirals in the NS3 and NS5A regions of Hepatitis C Virus (HCV) genotype 1B
Grantee:Nayara Nathie Marques
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/05975-3 - Investigation of the prevalence of resistance mutations to Sofosbuvir in the NS5B region of Hepatitis C Virus genotype 1B (HCV G1b)
Grantee:Bárbara Floriano Molina
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/03807-0 - Study of resistance mutations to treatment with Directly Acting antivirals in patients infected with hepatitis C virus genotype 3
Grantee:Guilherme Rodrigues Fernandes Campos
Support Opportunities: Scholarships in Brazil - Doctorate