Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

Zeuzem, Stefan; Hézode, Christophe; Bronowicki, Jean–Pierre; Loustaud‐Ratti, Véronique; Gea, Francisco; Buti, María; Olveira, Antonio; Bányai, Tivadar; Al-Assi, M. T.; Petersen, J.; Thabut, Dominique; Gadano, Adrián; Pruitt, Ronald E.; Makara, Mihály; Bourlière, Marc; Pol, Stanislas; Beumont–Mauviel, Maria; Ouwerkerk‐Mahadevan, Sivi; Picchio, Gastón; Bifano, Marc; McPhee, Fiona; Boparai, Navdeep; Cheung, Kin Jip; Hughes, Eric; Noviello, Stephanie

doi:10.1016/j.jhep.2015.09.024

Cited by 46 publications

(49 citation statements)

References 15 publications

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“…Antiviral therapy response and optimal treatment duration may vary based on the genotype/subtype of infection. HCV-infected, genotype 1b treatment-naive patients treated for 12 weeks with either daclatasvir and simeprevir or daclatasvir, simeprevir, and ribavirin achieved a higher rate of sustained virologic response at posttreatment week 12 (SVR12) than HCV-infected genotype 1a treatment-naive patients with 24 weeks of daclatasvir, simeprevir, and ribavirin (32). For the TURQUOISE-II study, HCV-infected genotype 1a patients needed to be treated for 24 weeks, instead of 12 weeks, with ombitasvir, paritaprevir, The same subtype was assigned by both methods.…”

Section: Discussionmentioning

confidence: 99%

Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6

Chodavarapu

Martin

et al. 2016

J Clin Microbiol

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Direct-acting antivirals (DAAs) with activity against multiple genotypes of the hepatitis C virus (HCV) were recently developed and approved for standard-of-care treatment. However, sequencing assays to support HCV genotype 5 and 6 analysis are not widely available. Here, we describe the development of a sequencing assay for the NS3/4A, NS5A, and NS5B genes from HCV genotype 5 and 6 patient isolates. Genotype-and subtype-specific primers were designed to target NS3/4A, NS5A, and NS5B for cDNA synthesis and nested PCR amplification. Amplification was successfully performed for a panel of 32 plasma samples from HCV-infected genotype 5 and 6 patients with sequencing data obtained for all attempted samples. LiPA 2.0 (Versant HCV genotype 2.0) is a reverse hybridization line probe assay that is commonly used for genotyping HCV-infected patients enrolled in clinical studies. Using NS3/4A, NS5A, and NS5B consensus sequences, HCV subtypes were determined that were not available for the initial LiPA 2.0 result for genotype 6 samples. Samples amplified here included the following HCV subtypes: 5a, 6a, 6e, 6f, 6j, 6i, 6l, 6n, 6o, and 6p. The sequencing data generated allowed for the determination of the presence of variants at amino acid positions previously characterized as associated with resistance to DAAs. The simple and robust sequencing assay for genotypes 5 and 6 presented here may lead to a better understanding of HCV genetic diversity and prevalence of resistance-associated variants. Globally, 130 to 150 million people have chronic hepatitis C virus (HCV) infection. Without treatment, chronic hepatitis may lead to liver cirrhosis and hepatocellular carcinoma and the possible need for a liver transplantation (1-3). Hepatitis C virus has high genetic diversity and is classified into seven genotypes and at least 67 subtypes among the genotypes (4, 5). At the nucleotide level for the open reading frame, there is a 31 to 33% difference between genotypes and 20 to 25% difference between subtypes (6).HCV genotype 1 is the most prevalent genotype and is widely distributed across the globe. Genotype 1 accounts for the majority of the HCV cases in North America, northern and western Europe, South America, Asia, and Australia (7,8). Similarly, genotypes 2 and 3 have broad geographical distribution. In contrast, genotypes 4, 5, and 6 are common only in specific regions. Genotype 4 and genotype 5 are endemic to Egypt and South Africa, respectively. Genotype 6 has the highest prevalence in Southeast Asia and southern China. Although genotypes 5 and 6 are not widespread, there are an estimated 9.8 million and 1.4 million people infected with genotypes 5 and 6, respectively, worldwide (9-13). Better treatment options are needed for genotype 5-and 6-infected patients.Due to the high prevalence and broad geographical distribution of genotype 1, early HCV research and development efforts were focused on this genotype. With the recent approval of HCV direct-acting antivirals (DAAs) active against multiple genotypes, such as Sovaldi (...

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Section: Discussionmentioning

confidence: 99%

Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6

Chodavarapu

Martin

et al. 2016

J Clin Microbiol

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“…DCV has been combined with other DAAs than SOF for the treatment of chronic hepatitis C. A randomized, open-label, phase 2 study evaluated a 12 or 24-week regimen of DCV at low dose (30 mg/day) plus SMV (NS3 protease inhibitor, 150 mg/day), with or without RBV (1000 mg daily if the body weight was <75 kg and 1200 mg if the body weight was ≥75 kg), in patients chronically infected with HCV genotype 1, mainly non-cirrhotics [30]. For genotype 1b, 84.9% and 74.5% of treatmentnaive patients, and 69.6% and 95.0% of null responders, achieved SVR12 with DCV plus SMV alone and with addition of RBV, respectively.…”

Section: Daclatasvir-based Regimenmentioning

confidence: 99%

Ideal oral combinations to eradicate HCV: The role of ribavirin

Hézode

Bronowicki

2016

Journal of Hepatology

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“…DCV has been studied in combination with the HCV protease inhibitor asunaprevir and a nonnucleoside NS5B inhibitor, beclabuvir, but these drugs are not available in the United States. DCV has also been studied with the HCV protease inhibitor simeprevir (SIM) [21]. However, the primary use of DCV in the United States is in combination with SOF.…”

Section: Daclatasvirmentioning

confidence: 99%

Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV

Miyagami

Kiser

2016

Clin Infect Dis.

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Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIVinfected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development.Keywords. hepatitis C virus; human immunodeficiency virus; coinfection; drug interactions; direct-acting antivirals.Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission [1,2]. HIV accelerates the progression of HCV disease. Individuals with HIV coinfection have higher HCV RNA, a more rapid progression of fibrosis, and an increased frequency of liver decompensation and death [3][4][5][6]. Due to the increased risks associated with HIV coinfection, treatment guidelines consider this patient population a "high priority" for HCV treatment [7,8].There have been significant advances in the treatment of HCV in recent years. Pegylated interferon alfa (PEG) and ribavirin (RBV) were the standard of care for this disease for decades, but several agents that directly target specific steps in the HCV lifecycle (Figure 1) have recently received regulatory approval [9]. The approved direct-acting antiviral agents (DAAs) inhibit 3 specific steps in the HCV lifecycle including the NS3/4A protease enzyme, NS5A protein, and the NS5B polymerase. Inhibition of the NS3 protease prevents the cleavage of the replication complex responsible for formation of viral RNA. The NS5B enzyme is essential for HCV replication as it catalyzes the synthesis of the complementary minus-strand RNA and subsequent genomic plus-strand RNA. There are 2 types of NS5B RNA-dependent RNA polymerase inhibitors: nucleotide and nonnucleoside inhibitors. The nucleotide inhibitors are active site inhibitors, whereas the nonnucleoside inhibitors are allosteric inhibitors. Another target, NS5A, encodes a protein that appears to be essential to the replication machinery of HCV and critical in the assembly of new infectious viral particles. However, the specific functions of this protein have not been established.Relative to PEG plus RBV, DAAs are well tolerated, administered for shorter treatment durations (eg, 8-24 weeks), and ultimately achieve high rates of cure (>90%), otherwise known...

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Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

Cited by 46 publications

References 15 publications

Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6

Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6

Ideal oral combinations to eradicate HCV: The role of ribavirin

Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV

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