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https://www.readbyqxmd.com/read/29221500/analysis-of-naturally-occurring-resistance-associated-variants-to-ns3-4a-protein-inhibitors-ns5a-protein-inhibitors-and-ns5b-polymerase-inhibitors-in-patients-with-chronic-hepatitis-c
#1
Danhui Sun, Mingjia Dai, Shanshan Shen, Chunyang Li, Xuebing Yan
The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011,and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with Hepatitis C virus (HCV). HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for treatment of HCV infection in combination with PEG-IFNα/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugsOur research showed that natural resistance to HCV DAAs was found in treatment-naïve CHC patients and that the drug resistance mutation rates differ in various HCV genotypes...
December 8, 2017: Gene Expression
https://www.readbyqxmd.com/read/29169329/micro-costing-analysis-of-guideline-based-treatment-by-direct-acting-agents-the-real-life-case-of-hepatitis-c-management-in-brazil
#2
Hugo Perazzo, Marcelino Jose Jorge, Julio Castro Silva, Alexandre Monken Avellar, Patrícia Santos Silva, Carmen Romero, Valdilea Gonçalves Veloso, Ruben Mujica-Mota, Rob Anderson, Chris Hyde, Rodolfo Castro
BACKGROUND: Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). METHODS: The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks...
November 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29167333/authentic-patient-derived-hepatitis-c-virus-infects-and-productively-replicates-in-primary-cd4-and-cd8-t-lymphocytes-in-vitro
#3
Georgia Skardasi, Annie Y Chen, Tomasz I Michalak
Accumulated evidence indicates that immune cells can support replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembled. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed properties of virus produced by these cells...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931406/validation-of-a-questionnaire-to-monitor-symptoms-in-hiv-infected-patients-during-hepatitis-c-treatment
#4
Edward R Cachay, Craig Ballard, Bradford Colwell, Francesca Torriani, Charles Hicks, Wm Christopher Mathews
BACKGROUND: Clinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy. DESIGN: Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV. METHODS: The HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC)...
September 20, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28904942/a-simple-but-accurate-method-for-evaluating-drug-resistance-in-infectious-hcvcc-system
#5
Jian-Rui Li, Wen-Jing Li, Jun-Jun Cheng, Meng-Hao Huang, Zhou-Yi Wu, Chen-Chen Jiang, Hu Li, Jin-Hua Chen, Xiao-Qin Lv, Biao Dong, Jian-Dong Jiang, Zong-Gen Peng
Use of direct-acting antivirals sometimes causes viral drug resistance, resulting in inefficiency in treated patients in real-world practice. Therefore, how to rapidly and accurately evaluate drug resistance is an urgent problem to be solved for rational use and development of antivirals in the future. Here, we aim to develop a new method by which we can evaluate easily but effectively whether a drug will still be efficient in the future treatment in infectious hepatitis C virus cell culture system. HCV-infected Huh7...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28901852/recent-advancement-of-direct-acting-antiviral-agents-daas-in-hepatitis-c-therapy
#6
Debasis Das, Mayank Pandya
Hepatitis C virus (HCV) infection is a major health burden worldwide. Approximately, 170-200 million individuals are chronically infected worldwide and a quarter of these patients are at increased risk of developing liver cirrhosis, hepatocellular carcinoma and even liver failure. A complete eradication of the virus is one of the most important treatment goal for antiviral research. In 2011, the first-generation protease inhibitors boceprevir (BOC) telaprevir (TVR) have been approved by FDA as the direct-acting antiviral agents...
September 12, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28856597/chemical-genetics-based-development-of-small-molecules-targeting-hepatitis-c-virus
#7
REVIEW
Guanghai Jin, Jisu Lee, Kyeong Lee
Hepatitis C virus (HCV) infection is a major worldwide problem that has emerged as one of the most significant diseases affecting humans. There are currently no vaccines or efficient therapies without side effects, despite today's advanced medical technology. Currently, the common therapy for most patients (i.e. genotype 1) is combination of HCV-specific direct-acting antivirals (DAAs). Up to 2011, the standard of care (SOC) was a combination of peg-IFNα with ribavirin (RBV). After approval of NS3/4A protease inhibitor, SOC was peg-IFNα and RBV with either the first-generation DAAs boceprevir or telaprevir...
September 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28856278/efficacy-of-hcv-treatment-in-poland-at-the-turn-of-the-interferon-era-the-epiter-study
#8
Robert Flisiak, Joanna Pogorzelska, Hanna Berak, Andrzej Horban, Iwona Orłowska, Krzysztof Simon, Ewelina Tuchendler, Grzegorz Madej, Anna Piekarska, Maciej Jabłkowski, Zbigniew Deroń, Włodzimierz Mazur, Marcin Kaczmarczyk, Ewa Janczewska, Arkadiusz Pisula, Jacek Smykał, Krzysztof Nowak, Marek Matukiewicz, Waldemar Halota, Joanna Wernik, Katarzyna Sikorska, Iwona Mozer-Lisewska, Błażej Rozpłochowski, Aleksander Garlicki, Krzysztof Tomasiewicz, Joanna Krzowska-Firych, Barbara Baka-Ćwierz, Wiesław Kryczka, Dorota Zarębska-Michaluk, Iwona Olszok, Anna Boroń-Kaczmarska, Barbara Sobala-Szczygieł, Bronisława Szlauer, Bogumiła Korcz-Ondrzejek, Jerzy Sieklucki, Robert Pleśniak, Agata Ruszała, Barbara Postawa-Kłosińska, Jolanta Citko, Anna Lachowicz-Wawrzyniak, Joanna Musialik, Edyta Jezierska, Witold Dobracki, Beata Dobracka, Jan Hałubiec, Rafał Krygier, Anna Strokowska, Wojciech Chomczyk, Krystyna Witczak-Malinowska
THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively...
December 2016: Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28856277/efficacy-and-direct-costs-of-chronic-hepatitis-c-treatment-with-first-generation-ns3-4a-protease-inhibitors-in-a-real-life-population
#9
Anna Piekarska, Ewa Koślińska-Berkan, Kamila Wójcik, Anna Skubała, Maciej Jabłkowski, Zbigniew Deroń, Aleksandra Berkan-Kawińska
INTRODUCTION: Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. MATERIAL AND METHODS: The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR...
December 2016: Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28845110/prioritization-for-interferon-free-regimens-and-potential-drug-interactions-of-current-direct-acting-anti-hepatitis-c-agents-in-routine-clinical-practice
#10
Μargarita Papatheodoridi, George N Dalekos, John Goulis, Spilios Manolakopoulos, Christos Triantos, Kalliopi Zachou, Argyro Koukoufiki, Αnastasia Κourikou, Κonstantinos Ζisimopoulos, Christos Τsoulas, George V Papatheodoridis
BACKGROUND: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs). METHODS: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/28815296/autoantibodies-against-rods-and-rings-related-impdh2-in-hepatitis-c-genotype-1-and-daa-therapy-in-a-real-life-cohort
#11
Werner Dammermann, Susanne Polywka, Inga Dettmann, Swantje Mindorf, Lars Komorowski, Malte Wehmeyer, Julian Schulze Zur Wiesch, Winfried Stöcker, Stefan Lüth
Autoantibodies against inosine-5'-monophosphate-dehydrogenase-2 (IMPDH2; "rods and rings" pattern) develop in chronic hepatitis C (CHC) patients under treatment with peg-interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. We investigated the influence of the alternative therapy with direct-acting antivirals (DAA)/ribavirin on anti-IMPDH2 autoantibody generation and the use of anti-IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). We analyzed a "real life" cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV-treated CHC GT1 patients...
October 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28736275/dendritic-cells-activation-is-associated-with-sustained-virological-response-to-telaprevir-treatment-of-hcv-infected-patients
#12
Alessandra Sacchi, Nicola Tumino, Federica Turchi, Giulia Refolo, GianMaria Fimia, Fabiola Ciccosanti, Marzia Montalbano, Raffaella Lionetti, Chiara Taibi, Gianpiero D'Offizi, Rita Casetti, Veronica Bordoni, Eleonora Cimini, Federico Martini, Chiara Agrati
First anti-HCV treatments, that include protease inhibitors in conjunction with IFN-α and Ribavirin, increase the sustained virological response (SVR) up to 80% in patients infected with HCV genotype 1. The effects of triple therapies on dendritic cell (DC) compartment have not been investigated. In this study we evaluated the effect of telaprevir-based triple therapy on DC phenotype and function, and their possible association with treatment outcome. HCV+ patients eligible for telaprevir-based therapy were enrolled, and circulating DC frequency, phenotype, and function were evaluated by flow-cytometry...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28680834/direct-acting-anti-hepatitis-c-virus-drugs-clinical-pharmacology-and-future-direction
#13
Ayman Geddawy, Yasmine F Ibrahim, Nabil M Elbahie, Mohammad A Ibrahim
Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors...
March 2017: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28658438/effectiveness-and-safety-of-first-generation-protease-inhibitors-in-real-world-patients-with-hepatitis-c-virus-genotype-1-infection-in-brazil-a-multicenter-study
#14
MULTICENTER STUDY
Luciana Azevedo Callefi, Cristiane Alves Villela-Nogueira, Simone de Barros Tenore, Dimas Carnaúba-Júnior, Henrique Sérgio Moraes Coelho, Paulo de Tarso A Pinto, Letícia Cancella Nabuco, Mário Guimarães Pessoa, Maria Lucia Cardoso Gomes Ferraz, Paulo Roberto Abrão Ferreira, Ana de Lourdes Candolo Martinelli, Silvana Gama Florencio Chachá, Adalgisa de Souza Paiva Ferreira, Alessandra Porto de Macedo Bisio, Carlos Eduardo Brandão-Mello, Mário Reis Álvares-Da-Silva, Tânia Reuter, Claudia Alexandra Pontes Ivantes, Renata de Mello Perez, Maria Cássia Jacintho Mendes-Correa
OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up...
June 2017: Clinics
https://www.readbyqxmd.com/read/28641714/hepatitis-c-treatment-in-patients-with-porphyria-cutanea-tarda
#15
Ashwani K Singal, Krishna V R Venkata, Sarat Jampana, Fakhar-Ul Islam, Karl E Anderson
BACKGROUND: Hepatitis C virus (HCV) infection is a common susceptibility factor for porphyria cutanea tarda (PCT). Experience on HCV treatment in patients with PCT is limited. Recently, HCV treatment has improved with direct-acting antivirals (DAA). We review our experience on HCV treatment in patients with PCT with older and newer regimens. MATERIALS AND METHODS: A retrospective chart review was conducted. HCV treatment was attempted 22 times in 13 patients with PCT (5 attempts in 1, 2 in 5 and 1 in the other 7 patients)...
June 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28636655/changes-in-inflammatory-biomarkers-in-hcv-infected-patients-undergoing-direct-acting-antiviral-containing-regimens-with-or-without-interferon
#16
Claudia Mascia, Serena Vita, Paola Zuccalà, Raffaella Marocco, Tiziana Tieghi, Stefano Savinelli, Raffaella Rossi, Marco Iannetta, Irene Pozzetto, Caterina Furlan, Fabio Mengoni, Claudio Maria Mastroianni, Vincenzo Vullo, Miriam Lichtner
BACKGROUND AND AIMS: Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). METHODS: sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens...
2017: PloS One
https://www.readbyqxmd.com/read/28603159/safety-profile-of-telaprevir-based-triple-therapy-in-elderly-patients-a-real-world-retrospective-cohort-study
#17
Maiko Akutagawa, Kazuki Ide, Yohei Kawasaki, Mie Yamanaka, Ryo Iketani, Hiroshi Yamada, Naohiko Masaki
To compare the rate of treatment discontinuation due to adverse events for telaprevir-based triple (T/PR) and pegylated interferon-alfa-2b and ribavirin (PR) therapy for the treatment of hepatitis C virus (HCV) infection in patients over the age of 65 years, in Japan.Retrospective analysis of the health data of patients over the age of 65 years treated for a HCV infection genotype 1 using T/PR or PR therapy, from 38 prefectures in Japan. The primary outcome was the rate of treatment discontinuation due to adverse events for T/PR and PR...
June 9, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28566078/-determination-of-drug-resistance-mutations-of-ns3-inhibitors-in-chronic-hepatitis-c-patients-infected-with-genotype-1
#18
Tamer Şanlıdağ, Murat Sayan, Sinem Akçalı, Elmas Kasap, Tahir Buran, Ayşe Arıkan
Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally...
April 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28545127/improvement-of-alt-decay-kinetics-by-all-oral-hcv-treatment-role-of-ns5a-inhibitors-and-differences-with-ifn-based-regimens
#19
Valeria Cento, Thi Huyen Tram Nguyen, Domenico Di Carlo, Elisa Biliotti, Laura Gianserra, Ilaria Lenci, Daniele Di Paolo, Vincenza Calvaruso, Elisabetta Teti, Maddalena Cerrone, Dante Romagnoli, Michela Melis, Elena Danieli, Barbara Menzaghi, Ennio Polilli, Massimo Siciliano, Laura Ambra Nicolini, Antonio Di Biagio, Carlo Federico Magni, Matteo Bolis, Francesco Paolo Antonucci, Velia Chiara Di Maio, Roberta Alfieri, Loredana Sarmati, Paolo Casalino, Sergio Bernardini, Valeria Micheli, Giuliano Rizzardini, Giustino Parruti, Tiziana Quirino, Massimo Puoti, Sergio Babudieri, Antonella D'Arminio Monforte, Massimo Andreoni, Antonio Craxì, Mario Angelico, Caterina Pasquazzi, Gloria Taliani, Jeremie Guedj, Carlo Federico Perno, Francesca Ceccherini-Silberstein
BACKGROUND: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. STUDY DESIGN: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR...
2017: PloS One
https://www.readbyqxmd.com/read/28539815/increase-of-soluble-programmed-cell-death-ligand-1-in-patients-with-chronic-hepatitis-c
#20
Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Shuji Terai
Objectives: To determine whether the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α. Methods: We investigated the sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin...
2017: International Journal of Medical Sciences
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