Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen

Objectives To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. Methods Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. Results We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. Conclusions One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.

DEPRESSIVE EPISODE INCIDENCE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGYLATED INTERFERON AND RIBAVIRIN

ABSTRACT Background The effectiveness of antiviral therapy with pegylated interferon and ribavirin for chronic hepatitis C is far from ideal and presents several adverse events. Among such events, there is the depressive episode that can even lead to treatment discontinuity Objective Analyze the incidence of depressive episodes in patients with chronic hepatitis C treated with pegylated interferon (IFN-PEG) and ribavirin, as well as the possible factors associated with its occurrence and its impact on patients' sustained virological response. Methods People with chronic hepatitis C undergoing antiviral therapy were interviewed at the baseline, at the 4th, 12th, 24th and 48th treatment weeks and 4 weeks after the end of it, using the HADS scale for tracking the depressive episode. Patients with HADS ≥9 were subjected to Beck Depression Inventory (BDI-II) to grade the episode. Clinical, sociodemographic, laboratorial and histological variables were obtained to identify factors related to the onset of depression. The sustained virological response rate (negative HCV-RNA 6 months after end of therapy) was compared among patients with and without depressive symptoms. Results The study comprised 32 patients, most men (59%) with mean age of 54±11.13 years old. Genotype non-1 was prevalent (56%) and 81% of the patients were non-cirrhotic. The depressive episode was diagnosed in 25% of the patients and the peak incidence was found in the 12th treatment week. The depressive episode was moderate in 87% of the patients and only one patient abandoned the treatment. None of the analyzed factors was associated with depressive episode onset. A trend was observed in female patients ( P=0.08). The sustained virological response rate was of 75% and 67% in patients with and without depressive episode, respectively (P =0.66). Conclusion The incidence of depressive episodes in patients with chronic hepatitis C undergoing antiviral therapy was of 25% and the 12th treatment week was the most critical one. The presence of depressive episode did not affect the sustained virological response rate.