1249 BI201335 PHARMACOKINETICS AND EARLY EFFECT ON VIRAL LOAD IN HCV GENOTYPE-1 PATIENTS

2011 ◽  
Vol 54 ◽  
pp. S493 ◽  
Author(s):  
C.-L. Yong ◽  
J. Scherer ◽  
J. Sabo ◽  
J.O. Stern ◽  
G. Steinmann ◽  
...  
Cytokine ◽  
2012 ◽  
Vol 57 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Juan Berenguer ◽  
Amanda Fernandez-Rodríguez ◽  
Maria Angeles Jimenez-Sousa ◽  
Jaime Cosín ◽  
Paola Zarate ◽  
...  

Vaccine ◽  
2012 ◽  
Vol 30 (19) ◽  
pp. 2943-2950 ◽  
Author(s):  
Christoph S. Klade ◽  
Elisabeth Schuller ◽  
Thomas Boehm ◽  
Alexander von Gabain ◽  
Michael P. Manns

Intervirology ◽  
2010 ◽  
Vol 53 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Taisuke Ueda ◽  
Hobyung Chung ◽  
Masatoshi Kudo ◽  
Emi Ishikawa ◽  
Sousuke Hayaishi ◽  
...  

2012 ◽  
Vol 17 (5) ◽  
pp. 849-854 ◽  
Author(s):  
Darrell HG Crawford ◽  
◽  
Gregory J Dore ◽  
William Sievert ◽  
Wendy SC Cheng ◽  
...  

2011 ◽  
Vol 92 (3) ◽  
pp. 497-499 ◽  
Author(s):  
N. Laufer ◽  
L. Abusamra ◽  
F. Bolcic ◽  
A. Gun ◽  
M.J. Rolón ◽  
...  

2015 ◽  
Vol 60 (3) ◽  
pp. 1546-1555 ◽  
Author(s):  
Eric J. Lawitz ◽  
William D. O'Riordan ◽  
Armen Asatryan ◽  
Bradley L. Freilich ◽  
Terry D. Box ◽  
...  

ABT-493 is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistancein vitro. In this open-label dose-ranging trial, antiviral activity and safety were assessed during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naive adults with HCV genotype 1 infection, with or without compensated cirrhosis. The presence of baseline resistance-associated variants (RAVs) was also evaluated. The mean maximal decreases in HCV RNA levels from baseline were approximately 4 log10IU/ml for all ABT-493 doses ranging from 100 mg to 700 mg and for ABT-530 doses of ≥40 mg. There were no meaningful differences in viral load declines for patients with versus without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without RAVs. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have a slightly less robust viral load decline on day 3 of monotherapy. No serious or grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound. ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection, with or without compensated cirrhosis. Based on these results, phase II studies assessing the combination of these DAAs for the treatment of chronic HCV infection in patients with or without compensated cirrhosis have been initiated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01995071.)


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shafiq Ur Rehman Cheema ◽  
Muhammad Salman Rehman ◽  
Ghulam Hussain ◽  
Sidra Shafiq Cheema ◽  
Nooman Gilani

Abstract Background There is paucity of data using direct anti-viral agents (DAA) in patients on maintenance hemodialysis (MHD) infected with HCV-genotype 1 & 3. Aim of the study was to evaluate DAA therapy in patients infected with HCV-genotype 1 & 3 on MHD. Methods A prospective open label, parallel, non-randomized interventional trial was conducted in patients with Hepatitis-C on maintenance hemodialysis. Total of Sixty two (62) patients with hepatitis-C on maintenance hemodialysis were screened and 36 patients were enrolled and then equally allocated in 1:1 ratio to group 1 who received 400 mg daily sofosbuvir/ 60 mg daily daclatasvir and group 2 who received thrice a week 400 mg Sofosbuvir and daily 60 mg daclatasvir for 12 weeks. Patients with compensated cirrhosis received therapy for 24 weeks. Relevant data was obtained before, during and after therapy. HCV viral load was assessed at week 4, 8, at end of therapy and 12 weeks after treatment. Results Eighteen (18) patients were allocated in each group. Three patients in group 1 withdrawn from the study after 2 weeks due to refusal to participate, while one withdrawn in group 2 due to development of adverse effect. Mean age of patients was 47.22 + 14.17 in group 1 and 53.89 + 14.11 in group 2. Genotype 3 was most common in group 1 patients, n = 12 (66.6%), and n = 11 (61.1%) in group 2. All patients in both groups achieved undetectable viral load at 12th week. As per intention to treat analysis overall 29/36 (80.55%) patients achieved SVR (group 1 = 15/18; group 2 = 14/18) and as per-protocol analysis overall 29/32 (90.62%) patients achieved SVR (group 1 = 15/15; group 2 = 14/17). Conclusion Direct acting antiviral therapy using sofosbuvir and declatsavir is highly effective and tolerable in patients with HCV genotype 1 & 3 undergoing maintenance hemodialysis, especially when given daily. Trial registration This trial is registered in WHO, International Clinical Trial Registry Platform, through Iranian Registry of Clinical Trials (IRCT) having IRCT ID: IRCT20170614034526N3, registered retrospectively on 2019-03-08.


2015 ◽  
Vol 29 (3) ◽  
pp. 125-129 ◽  
Author(s):  
Sergio M Borgia ◽  
Adenike Rowaiye

BACKGROUND: All oral, highly effective direct-acting antiviral combinations, such as sofosbuvir-ledipasvir, have recently been licensed in Canada but cost as much as $67,000 for a 12-week course of therapy, representing a major economic barrier to predominately single-payer health care systems such as that found in Ontario. In hepatitis C virus (HCV) genotype 1 noncirrhotic patients with a baseline viral load of <6×106IU/mL, treatment with sofosbuvir-ledipasvir can be shortened to eight weeks without compromising ≥95% efficacy. The number of HCV-infected patients in Ontario eligible for shortened therapy, and the associated cost savings, are unknown. The authors propose that treating every patient with shortened therapy, regardless of baseline viral load, would lead to significant public cost savings and collateral efficiencies, enabling increased HCV treatment capacity and cure.METHODS: The present study designed a three-part model to investigate the cost of cure per patient and cost savings per patient under three eligibility pathways: conservative, permissive and ideal. In the conservative model, every patient is treated for 12 weeks regardless of baseline viral load, whereas in the permissive model, patients with a baseline viral load <6×106IU/mL are treated for eight weeks. In the ideal model, every patient receives eight weeks of therapy regardless of baseline viral load. Relapsed patients are retreated for 12 weeks. Data obtained from the Ontario Public Health Laboratory were used to validate the model and generate the outcomes.RESULTS: In Ontario, 75.34% of HCV genotype 1 patients had a baseline viral load of <6×106IU/mL and were eligible for shortened therapy. The cost of cure per patient in the ideal model was $47,328.44, representing a 29% reduction in the cost of curative therapy and 3.5 weeks of shortened treatment duration compared with the conservative model. The ideal model generated a cost savings per patient of $3,855.17 (8% reduction in treatment cost) and 0.7 weeks of shorter therapy compared with the permissive model, and was the shortest and most efficient while maintaining a cure rate ≥95%.CONCLUSIONS: These results demonstrate that recommendations for a shortened treatment course of eight weeks using all-oral direct-acting antivirals in HCV genotype 1 noncirrhotic patients, regardless of baseline viral load, affords significant public cost savings and, on a population level, offers opportunities for expanded HCV treatment and cure.


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