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      Very rapid virologic response and early HCV response kinetics, as quick measures to compare efficacy and guide a personalized response-guided therapy

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          Abstract

          Background

          This is the second and final report for our study designed to compare two generic sofosbuvir products for the degree and speed of virologic response to a dual anti-hepatitis C virus (HCV) treatment protocol. We aimed to test the applicability of the early virus response kinetics and the very rapid virologic response (vRVR) rate as quick outcome measures for accelerated comparative efficacy studies and as a foundation for a personalized response-guided therapy.

          Methods

          Fifty eligible chronic HCV patients were randomized to either one of two generic sofosbuvir products (Gratisovir or Grateziano) at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose. Data were compared between the groups for early virus response kinetics and vRVR rates in relation to the rates of final sustained virologic response at week 12 posttreatment (SVR12).

          Results

          The Log 10 transformed virus load (Log polymerase chain reaction) curves showed fairly similar rapid decline during the first 2 weeks, with no significant difference between the groups at four analysis points throughout the study by repeated-measures factorial analysis of variance test ( P=0.48). The SVR12 rates were 96% (95% confidence interval, 79.6%–99.9%) in Gratisovir group (24/25) and 95.7% (95% confidence interval, 78%–99.9%) in Grateziano group (22/23). There was no statistically significant difference found by exact test ( P>0.999). There was a significant association between the vRVR and the SVR12, with 100% positive predictive value (38/38 of those who had vRVR, achieved a final SVR12) and 82.6% sensitivity (among the total 46 with SVR12, 38 were having vRVR).

          Conclusion

          We can conclude from our study that the early HCV response kinetics and the vRVR rates could be used as sensitive quick markers for efficacy (with a very high positive predictive value for SVR12), based on our accelerated comparative efficacy research model. This might open the way for new models of accelerated equivalence efficacy studies along with the bioequivalence kinetics studies to test a generic drug against a reference. Also, the early response kinetics and the vRVR might be used as qualifiers for a personalized course of treatment. This could shorten unnecessarily long treatment courses in rapid responders and might help to avoid relapses in slow responders.

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          Most cited references 11

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          HCV direct-acting antiviral agents: the best interferon-free combinations.

          For HCV infection, there have been major advancements during last several years with large numbers of ongoing trials with various direct-acting antivirals (DAA) showing high potency, favourable tolerability profile, higher barrier to resistance, shortened treatment duration, all oral regimen, pan-genotypic, fewer drug interactions and reduced pill burden. By 2014, several DAAs are anticipated to complete successful phase III trials and will be commercially available. Initially, a wave of IFN-based regimen (sofosbuvir, faldaprevir and simeprevir) will be available for treatment of HCV genotype 1. In the near future, combination of antiviral agents with additive potency that lack cross-resistance with good safety profile will likely be the new recommended regimens, making HCV, the first chronic viral infection to be eradicated worldwide with a finite duration of combination DAA therapy without IFN or ribavirin. The aim of this review was to summarize the results obtained from recent DAA combination studies without IFN. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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            HCV burden of infection in Egypt: results from a nationwide survey.

            Egypt is the country with the largest hepatitis C virus (HCV) epidemic in the world. In 2008, a Demographic Health Survey (DHS) was carried out in Egypt, providing for the first time a unique opportunity for HCV antibody testing on a nationwide representative sample of individuals. Consenting individuals answered a questionnaire on socio-demographic characteristics and iatrogenic exposures, before providing a blood sample for HCV antibody testing by enzyme-linked immunosorbent assay. Factors independently associated with HCV infection were examined through multivariate logistic regression models. Of 12 780 eligible subjects aged 15-59 years, 11 126 (87.1%) agreed to participate and provided a blood sample. HCV antibody prevalence nationwide was 14.7% (95% CI 13.9-15.5%) in this age group. HCV antibody prevalence gradually increased with age, reaching, in the 50-59 years age group, 46.3% and 30.8% in males and females, respectively. It was higher in males compared to females (17.4% versus 12.2%, respectively, P < 0.001), and in rural compared to urban areas (18.3% versus 10.3%, respectively, P < 0.001). In multivariate analysis, age, male sex, poverty, past history of intravenous anti-schistosomiasis treatment, blood transfusion, and living outside of the Frontier Governorates were all significantly associated with an increased risk of HCV infection. In addition, in urban areas, lack of education and being circumcised for females were associated with an increased risk of HCV infection. This study confirmed on a nationwide representative sample the very high HCV antibody prevalence in Egypt. It stresses the urgent need for strengthening prevention efforts, and bringing down the costs of antiviral drugs for countries like Egypt, where the people in the most precarious situations are also those most likely to be infected by the virus. © 2012 Blackwell Publishing Ltd.
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              Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4.

              Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype 4 virus. We evaluated the efficacy and safety of the HCV polymerase inhibitor sofosbuvir in combination with ribavirin in HCV genotype 4 patients in Egypt.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                25 August 2016
                : 10
                : 2659-2667
                Affiliations
                [1 ]Green Clinical Research Center
                [2 ]Abbas Helmy Clinics
                [3 ]Tropical Medicine and Hepatology Department, Alexandria Faculty of Medicine
                [4 ]Microbiology Department, High Institute of Public Health, Alexandria University
                [5 ]Mabarat Asafra Labs
                [6 ]Pharco Corporation, Alexandria, Egypt
                Author notes
                Correspondence: Mostafa Yakoot, Green Clinical Research Center, 27 Green Street, Alexandria 21121, Egypt, Tel +20 3 122 392 7561, Email yakoot@ 123456yahoo.com
                Article
                dddt-10-2659
                10.2147/DDDT.S111496
                5003574
                27601883
                © 2016 Yakoot et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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