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Protease, Polymerase, and Assembly Inhibitors for the Treatment of Hepatitis C Virus Infection
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
Marianne Martinello, Jason Grebely, Gregory Dore
Dasabuvir is a nonnucleoside RdRp inhibitor approved for use in HCV genotype 1 infection in combination with ombitasvir and ritonavir-boosted paritaprevir (Gentile et al., 2014b). After exposure to dasabuvir in HCV genotype 1a replicons, single NS5B substitutions C316Y, M414I/T, E446K/Q, Y448C/H, A553T, G554S, S556G/R, and Y561H reduced dasabuvir antiviral activity by 8- to 1472-fold, whereas in genotype 1b replicons, single NS5B substitutions C316H/N/Y, S368T, N411S, M414I/T, Y448C/H, A553V, S556G, and D559G reduced dasabuvir antiviral activity by 5- to 1569-fold (AbbVie, 2015).
Cost-effectiveness of novel regimens for Chinese patients with chronic hepatitis C
Published in Current Medical Research and Opinion, 2019
Bin Wu, Zhenhua Wang, Qing Xie
The recent rapid development of direct-acting antiviral (DAA) therapies for HCV infection, such as daclatasvir + asunaprevir, ombitasvir/paritaprevir/ritonavir/+dasabuvir, and sofosbuvir + ledipasvir provides shorter, simpler, and safer regimens with improved SVR and safety profiles in comparison with interferon-based regimens. These interferon-free regimens are highly effective and well-tolerated treatment options for East Asian patients with HCV genotype 1b infection4, which is the predominant genotype (56.8%) in China, followed by genotypes 2, 3, and 65,6. In Asian patients with HCV, the use of interferon-free regimens also leads to greater patient-reported outcomes during treatment7. Recently, sofosbuvir, daclatasvir, asunaprevir, ombitasvir/paritaprevir/ritonavir, and dasabuvir have been licensed by the Chinese State Food and Drug Administration. However, due to the expensive nature of DAAs, their wide prescription was limited in a health resource-limited context, especially where inexpensive generic interferon α plus ribavirin is still one of the main treatment alternatives. At this stage, however, it is unclear whether these novel DAAs could represent a cost-effective strategy for treating Chinese patients. Therefore, this study aimed to examine the health and economic outcomes of novel regimens containing DAAs and pegylated interferon α-based treatments for managing genotype 1b, 2, 3, and 6 HCV infections in the context of Chinese patients.
Dynamics and management of oral anticoagulant treatment in chronic hepatitis C patients undergoing therapy with direct antiviral agents
Published in Journal of Chemotherapy, 2019
Martina Vitrone, Antonio Parrella, Rosina Albisinni, Emanuele Durante-Mangoni, Rosa Zampino
Current regimens of direct-acting antiviral agents (DAA) are well tolerated, very safe and effective, with sustained virological response (SVR) rates, denoting cure of the infection, >95%. These drugs include (i) inhibitors of hepatitis C virus (HCV) polyprotein maturation (NS3-4A protease inhibitors (PI), such as simeprevir, paritaprevir, grazoprevir, glecaprevir, voxilaprevir), (ii) HCV-RNA polymerase inhibitors (sofosbuvir, dasabuvir) and inhibitors of polymerase cofactor NS5A (daclatasvir, ombitasvir, ledipasvir, velpatasvir, pibrentasvir, elbasvir).6,7 In patients with advanced fibrosis and cirrhosis, SVR reduces the rate of decompensation and can also reduce, but not abolish, the risk of hepatocellular carcinoma.8 However, DAA often interfere with concurrent medications, with potentially harmful consequences.9
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
Since then, more effective DAAs have been approved by the European Medicines Agency (EMA) and US Food and Drugs Administration (FDA) to treat patients with chronic HCV infection. The newer drugs have excellent tolerance and SVR rates. These newer medications opened up a new scenario in HCV therapy: elimination of Peg-IFN, shorter duration of treatment, lower toxicity, and higher compliance [8]. Sofosbuvir (SOF), a nucleotide NS5B polymerase inhibitor, was the first of the second-generation DAA [9]. It was followed by the NS3/4A protease inhibitor simeprevir (SMV) [8] and two NS5A inhibitors, ledipasvir (LPV) [10] and DCV [11]. In 2014, two fixed-dose drug combinations were approved for HCV management: SOF/LPV [12] and paritaprevir/ombitasvir/ritonavir with dasabuvir [13].