scholarly journals The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 16
Author(s):  
Stephanie Popping ◽  
Valeria Cento ◽  
Carole Seguin-Devaux ◽  
Charles Boucher ◽  
Adolfo de Salazar ◽  
...  

Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno—and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0–48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients’ characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm.

2021 ◽  
Vol 27 (2) ◽  
pp. 42-48
Author(s):  
Ayhan Balkan ◽  
Yasemin Balkan ◽  
Abdullah Emre Yıldırım ◽  
Buğra Tolga Konduk ◽  
Sezgin Barutçu ◽  
...  

2020 ◽  
Vol 15 (3) ◽  
Author(s):  
Narjes Shokatpour ◽  
Shahnaz Sali ◽  
Batool Daneshpazhouh ◽  
Masoud Mardani

Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents in patients with HCV/human immunodeficiency virus (HIV) co-infection remains controversial due to drug interactions with antiretroviral therapy (ART). Objectives: In this study, we assessed the efficacy and tolerability of daclatasvir/sofosbuvir (DCV/SOF) in patients with HIV-HCV co-infection in the real-life setting in Iran. Methods: A total of 44 patients with HCV-HIV co-infection (genotypes 1, 3, and 4) were treated with DCV/SOF±RBV (ribavirin) (dose-adjusted DCV for concomitant ART). Assessment of risk factors, sustained virologic response at 12 weeks after the end of treatment (SVR12), safety, and serum CD4 count was performed. Results: Most patients were male (95.2%). Four patients were HCV treatment-experienced cases, and 15 had cirrhosis or advanced fibrosis. The most common genotype was 3 (53.5%), followed by 1 (44.2%) and 4 (2.3%). HIV-1 RNA < 50 copies/mL and CD4 count > 250 cells/mm3 were observed in 81.8% and 79.1% of patients, respectively. The highest risk factor was a history of IV drug use (81.8%), followed by using a common syringe (77.3%) and tattooing (70.5%). All patients with or without cirrhosis (100%) completed the HCV treatment course and achieved SVR12. Also. 92.6% of patients on ART had CD4 count > 250 cells/mm3 at the end of treatment. The HCV treatment regimen was well-tolerated. Moreover, 15.9% of patients experienced adverse events (AEs), including anorexia, nausea, diarrhea, palpitations, and anxiety. No serious AEs or discontinuation due to AEs were reported. Conclusions: Our study showed excellent tolerability and efficacy of DCV/SOF±RBV in HIV-HCV co-infected patients with or without cirrhosis.


2021 ◽  
Vol 25 ◽  
pp. 100337
Author(s):  
Fabrizio Fabrizi ◽  
Cristina Alonso ◽  
Ana Palazzo ◽  
Margarita Anders ◽  
Maria Virginia Reggiardo ◽  
...  

2018 ◽  
Vol 4 (3) ◽  
pp. 179-181 ◽  
Author(s):  
Stephanie Popping ◽  
Valeria Cento ◽  
Federico García ◽  
Francesca Ceccherini-Silberstein ◽  
Carole Seguin-Devaux ◽  
...  

2016 ◽  
Vol 10 (1) ◽  
pp. 155-167 ◽  
Author(s):  
Anaïs Vallet-Pichard ◽  
Stanislas Pol

Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8–24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance. SVR rates and safety are similar in clinical trials and in real life, usually higher than 95% in the per-protocol analysis. Next-generation DAAs are now expected. To be competitive, these new combinations need to prove their added value regarding the pill burden, the reduced duration of treatment, the drug–drug interaction profile and safety. Zepatier is a fixed-dose combination product coformulating MK-5172 [grazoprevir (GZR), 100 mg QD] and MK-8742 [elbasvir or (EBR) 50 mg QD]: it combines highly potent inhibitors of the HCV NS3/4A protease and NS5A replication complex, respectively. This review provides a summary of the main evidence available for the use of GZR/EBR and highlights the strength of this combination.


2019 ◽  
Vol 39 (03) ◽  
pp. 341-353 ◽  
Author(s):  
Sasha R. Fehily ◽  
Tim Papaluca ◽  
Alexander J. Thompson

AbstractMore than 70 million people are chronically infected with hepatitis C virus (HCV) worldwide. Chronic hepatitis C is associated with progressive liver fibrosis, which can result in cirrhosis, liver failure, and hepatocellular carcinoma (HCC). HCV-related liver disease has been the most common indication for liver transplantation in the past decade. The development of direct-acting antiviral agents (DAAs) that are simple, well-tolerated, and highly effective means that most people living with hepatitis C can now be cured, leading the World Health Organization to set targets for reduction in deaths due to viral hepatitis by 2030. In this review, the authors will consider the emerging data showing that curative therapy with DAAs can prevent HCV-related morbidity and mortality, with a focus on patients with HCV-related cirrhosis.


2018 ◽  
Vol 68 ◽  
pp. S304-S305
Author(s):  
V.C. Di Maio ◽  
V. Cento ◽  
V. Micheli ◽  
C. Masetti ◽  
C.F. Magni ◽  
...  

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