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Author Notes:

skon@usp.br

The principal investigators, RM Abreu and SK Ono, were responsible for the conception and design of the study, the acquisition, analysis and interpretation of the data, and the drafting of the manuscript. LC Bassit, S Tao, Y Jiang, AS Ferreira, PCA Hori, LM Ganova-Raeva, and Y Khudyakov helped with the design of the study, acquisition of the data, and critical revision of the manuscript regarding intellectual content. RF Schinazi, FJ Carrilho, and SK Ono guided the study and provided input on assays to be performed and helped write and review this paper.

We thank the Alves de Queiroz Family Fund for Research for support of studies, James J. Kohler (Emory University) for manuscript review, Dimitri Gonzalez and Chalom Sayada (Advanced Biological Laboratories – ABL, Luxemburg, Belgium) for the use of DeepChek®–HBVv1.4 software for genotyping and drug resistance analysis. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Finally, we greatly thank all patients for their consent and participation in the study and for the research use of their plasma specimens.

A part of this study was presented at the AASLD The Liver Meeting, San Francisco, on 16 Nov, 2015. No commercial funding was involved in this study.

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Research Funding:

This research was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq number 201812/2014–2 to RMA), (CNPq number 308609/2018–2 and 551407/2007–7 to SKO), SPRINT-Emory FAPESP (2017/50042–2) and in part by NIH sponsored Center for AIDS Research Grant P30AI050409 and 1R01AI132833 (to RFS).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Infectious Diseases
  • Pharmacology & Pharmacy
  • Virology

Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study

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Journal Title:

ANTIVIRAL THERAPY

Volume:

Volume 24, Number 8

Publisher:

, Pages 567-579

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. Methods: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named 'Assessment of Adherence to Antiviral Therapy Questionnaire' (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015). Results: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by nonadherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Longterm evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001). Conclusions: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNAnegative group.

Copyright information:

2019

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