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      Effectiveness of implementing a decentralized delivery of hepatitis C virus treatment with direct-acting antivirals: A systematic review with meta-analysis

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          Abstract

          Direct-acting agents (DAAs) for hepatitis C virus (HCV) treatment are safe and highly effective. Few studies described the sustained virologic response rates of treatment conducted by non-specialists. We performed a systematic review and meta‐analysis to evaluate the effectiveness of decentralized strategies of HCV treatment with DAAs. PubMed, Embase, Scopus and LILACS were searched until March-2019. Studies were screened by two researchers according to the following inclusion criteria: HCV treatment using DAAs on real-life cohort studies or clinical trials conducted by non-specialized health personnel. The primary endpoint was the sustained virologic response rate at week 12 after the end-of-treatment (SVR12), which is binary at the patient level. Data were extracted in duplicate using electronic-forms and quality appraisal was performed with the NIH Quality Assessment Tool. Heterogeneity was assessed by I 2 statistics. Random-effects meta-analysis models were used for pooling SVR12 rates. Publication bias was assessed using funnel plots. Among the 130 selected studies, nine papers were included for quantitative synthesis. The quality-appraisal was good for two, fair for three and poor for four studies. The pooled relative risk (RR) of SVR12 was not statistically different between decentralized strategy and treatment by specialists [RR = 1.05; 95% confidence interval (95% CI): 0.98–1.1; I 2 = 45% (95% CI: 0–84%), p = 0.145]. SVR12 rate for decentralized HCV treatment was 81% [SVR12 95% CI: 72–89%; I 2 = 93% (95% CI: 88–96%)] and 95% [SVR12 95%CI: 92–98%; I 2 = 77% (95% CI: 52–89%)] with intention to treat analysis and per-protocol analysis, respectively. SVR12 rates using DAAs managed by non-specialized health personnel were satisfactory and similar to those obtained by specialists. This new delivery strategy can improve access to HCV treatment, especially in resource-limited settings. PROSPERO #: CRD42019122609.

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          Most cited references34

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          Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study

          Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.
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            Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System.

            We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or 4.
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              Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort.

              Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Writing – review & editing
                Role: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 February 2020
                2020
                : 15
                : 2
                : e0229143
                Affiliations
                [1 ] Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública Sergio Arouca, Rio de Janeiro, RJ, Brazil
                [2 ] Universidade Federal do Estado do Rio de Janeiro, Instituto de Saúde Coletiva, Rio de Janeiro, RJ, Brazil
                [3 ] Fundação Oswaldo Cruz, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, RJ, Brazil
                Middle East Liver Diseases (MELD) Center, ISLAMIC REPUBLIC OF IRAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-0701-2528
                Article
                PONE-D-19-24548
                10.1371/journal.pone.0229143
                7034833
                32084187
                57880f2c-0b90-48c8-8ef4-be45dc06acb1
                © 2020 Castro et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 August 2019
                : 30 January 2020
                Page count
                Figures: 5, Tables: 1, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: PIBIC
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: PIBIC
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: PIBITI
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: PIBITI
                Award Recipient :
                Funded by: Instituto Nacional de Infectologia Evandro Chagas
                Award ID: Programa de Incentivo a Jovens Pesquisadores
                Award Recipient :
                This study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq ( http://cnpq.br/) through these research grants: Programa Institucional de Bolsas de Iniciação Científica - PIBIC/CNPq ( http://cnpq.br/pibic) [RC, LAMMA], Programa Institucional de Bolsas de Iniciação em Desenvolvimento Tecnológico e Inovação - PIBITI/CNPq ( http://cnpq.br/pibiti) [RC,IGG] at Fundação Oswaldo Cruz (FIOCRUZ), and Programa de Incentivo a Jovens Pesquisadores at Instituto Nacional de Infectologia Evandro Chagas - INI/FIOCRUZ ( https://www.ini.fiocruz.br/) [HP]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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