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

• Published in: Clinics and research in hepatology and gastroenterology 2020-06, Vol.44 (3), p.329-339
• Main Authors: Aguiar, Bruna Forte, Campos, Guilherme Rodrigues Fernandes, Rodrigues, João Paulo Vilela, Marques, Nayara Nathie, Molina, Bárbara Floriano, Bittar, Cintia, Souza, Fernanda Fernandes, Martinelli, Ana de Lourdes Candolo, Rahal, Paula, Pereira, Leonardo Régis Leira
• Format: Article
• Language: English
• Subjects: Antiviral resistance; Baseline mutations; DAA treatment; Genotype 1; HCV
• ISSN: 2210-7401; 2210-741X
• DOI: 10.1016/j.clinre.2019.07.015

•The sustained virological response at 12 weeks post-treatment 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.•Out of 144 blood samples, 70 (48.6%) had detected resistance associated substitutions (34.8% treated with SOF+DCV±ribavirin and 61.3% SOF+SMV±ribavirin).•Important mutations associated with resistance against DAAs were detected in NS3 (G122S, I170V, Y56F and V132I), NS5A (R30Q, P58H and Q62E) and NS5B (A421V, L159F and C316N).•Three out of 4 relapsing patients presented virus carrying baseline resistance substitutions.•Substitutions with direct effect on virus resistance were observed occurring simultaneously with compensatory mutations that can improve virus replication. 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. 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. 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. 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