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Ribavirin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Emily Woolnough, Amanda Wade, Joe Sasadeusz
After these treatment successes with serine protease inhibitors, attention turned to novel therapeutic targets important for hepatitis C viral assembly and replication. NS5A inhibitors, including daclatasvir and ledipasvir, act against a protein critical to both of these processes. In the COMMAND phase II trials, daclatasvir was combined with peginterferon–ribavirin for the treatment of HCV genotypes 1, 2 and 3. SVR rates were 83–88% at 12 and 16 weeks for genotype 2 but lower for genotypes 1 and 3 (Hezode et al., 2012; Dore et al., 2013). Further innovation in this field led to the development of NS5B inhibitors, which target the RNA-dependent RNA polymerase responsible for viral replication. Although there are several agents in various stages of development, sofosbuvir recently became the first NS5B inhibitor to be licensed for clinical use. In one large phase III study, 327 treatment-naive patients with genotype 1, 4, 5, or 6 demonstrated SVR rates of 90% when sofosbuvir was used in combination with peginterferon–ribavirin (Lawitz et al., 2013). The efficacy of triple therapy with sofosbuvir and peginterferon–ribavirin has also been established in patients with genotype 2 or 3 disease, including those with compensated cirrhosis (Lawitz et al., 2013).
Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal
Published in Postgraduate Medicine, 2023
Cristina Burgui, Ramón San Miguel, Silvia Goñi-Esarte, Regina Juanbeltz, Juan Isidro Úriz-Otano, Jesús Reparaz, Maite Sarobe, José Manuel Zozaya, Jesús Castilla
Previous treatments with interferon had limited efficacy and frequent side effects [12]. In 2011, first-generation direct-acting antivirals improved the efficacy, but still with significant adverse effects [13]. However, since 2013 highly effective and safe second-generation direct-acting antivirals (DAAs) have markedly changed the landscape of treatment of HCV infection. DAAs are combinations of two or more HCV antiviral drugs such as simeprevir, sofosbuvir, ledipasvir, daclatasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, elbasvir, grazoprevir, glecaprevir, pibrentasvir, velpatasvir and voxilaprevir, with or without ribavirin. The first clinical trials demonstrated efficacies above 90% in achieving SVR [14–22], and effectiveness estimates were even better in further observational studies [23–25].
Daclatasvir as a hepatitis C infection treatment option: an up-to-date evaluation
Published in Expert Opinion on Pharmacotherapy, 2023
Nirmeen Sabry, Ahmed M. Kamel, Ahmed Cordie, Gamal Esmat
According to the WHO, it is estimated that 58 million individuals are infected with hepatitis C virus (HCV), with approximately 1.5 million new cases occurring each year [1]. HCV is a major cause of end-stage liver disease and hepatocellular carcinoma [2]. Globally, the WHO estimated that 290,000 HCV patients died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019 [1]. Till 2011, the standard of care for the management of HCV infection was pegylated interferon (Peg-IFN) and ribavirin (RBV) combination. Nonetheless, the combination was associated with high rates of adverse effects and low rates of sustained virological response (SVR) [3]. This review aims to update the existing evidence regarding the safety, efficacy, and cost-effectiveness of daclatasvir (DCV) as an HCV treatment option based on real-world studies and more recent pharmacoeconomic (PE) evaluations to assess its current and potential future role as an HCV treatment option.
Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials
Published in Expert Review of Anti-infective Therapy, 2022
Chia Siang Kow, Amaan Javed, Dinesh Ramachandram, Syed Shahzad Hasan
Sofosbuvir–daclatasvir is an effective direct-acting antiviral agent against the hepatitis C virus. Sofosbuvir inhibits NS5B-RdRp, a crucial enzyme in replicating hepatitis C virus, while ledipasvir inhibits NS5A, an essential protein for RdRp function. An in-silico study reported that sofosbuvir and daclatasvir could have theoretical antiviral activity against SARS-CoV-2 due to their predictive ability to bind to RdRp and Mpro with high energy. Therefore, they are attractive to be repurposed for the treatment of COVID-19 [3,4]. Indeed, in an in vitro study [5], sofosbuvir and daclatasvir demonstrated antiviral activity against SARS-CoV-2-infected Huh-7 and Calu-3 cells. In the same study [5], daclatasvir demonstrated antiviral activity against Vero E6-infected cells but not for sofosbuvir. Sofosbuvir has also exhibited neutralizing activity against SARS-CoV-2-infected brain organoids, suggesting its potential protective effects against COVID-19 related neurological complications [6].