A SHORT COURSE OF TRIPLE TELAPREVIR-BASED ANTIVIRAL THERAPY: THE PRINCIPLES OF PATIENTS SELECTION

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Abstract

Background: The beginning of a new era of direct acting antivirals sets up its own rules, that is, to achieve the highest efficacy with the shortest duration of treatment. It is assumed that the use of the first generation of direct acting antivirals, similarly to interferon-free regimens, would allow for personalization of approaches to their prescriptions.
Aim: To identify the most important parameters that can predict the greatest efficacy of triple antiviral therapy of 12 week duration in patients with chronic hepatitis C genotype 1.
Materials and methods: The study included 204 patients with chronic hepatitis C virus (HCV) genotype 1 at an early stage of liver disease (METAVIR score F0-F2), who were either treatment-naive or had a history of relapse after standard of care antiviral therapy. In addition to routine work-up, all patients were screened for IL28B polymorphism; in the course of the treatment viral kinetics was assessed by an ultrasensitive polymerase chain reaction (PCR) (with lower limit of quantification of 12 IU/ml). Duration of the triple therapy (pegylated interferon-α2a, ribavirin and telaprevir) was reduced to 12 weeks if a rapid virological response was achieved; otherwise the patients continued their treatment in according with guidelines.
Results: A complete rapid virological response was achieved in 174 patients (81.6%), in whom the duration of triple therapy was 12 weeks. According to the protocol, 25 patients with a partial rapid virological response continued their standard antiviral therapy for 12 weeks more. In those who achieved a rapid virological response, there was an association between IL28B-CC genotype at rs12979860 and maintenance of zero viremia at 12 weeks after termination of antiviral therapy (r = 0.38, p < 0.001). In all such patients there was a stable virological response at 12 weeks of the follow-up. Monitoring of viral load after 14 days of antiviral treatment was not predictive of its success. The preliminary results of a shortened (12 week) course of triple telaprevir-based viral therapy allowed to identify the most significant parameters of 100% efficacy, i.e., absence of the virus in blood at 12 weeks after termination of antiviral therapy.
Conclusion: A 12 week course of triple telaprevir-based combination therapy is an optimal regimen for achievement of a stable virological response after 12 weeks of the follow-up in treatment-naïve patients with HCV genotype 1 or with a relapse after previous conventional antiviral treatment, who have IL28B – CC polymorphism, are at an early stage of liver disease and who achieve a rapid complete virological response confirmed by a highly sensitive PCR.

About the authors

P. O. Bogomolov

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Bogomolov Pavel Olegovich – PhD, Deputy Chief Physician in Clinical and Diagnostic Operations,Head of the Moscow Regional Hepatology Center Russian Federation

M. V. Matsievich

Moscow Regional Research and Clinical

Author for correspondence.
Email: macievich@gmail.com
Matsievich Mariya Vladislavovna – PhD, Research Fellow, Department of Gastroenterology and Hepatology Russian Federation

K. Yu. Kokina

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Kokina Kseniya Yur'evna – Gastroenterologist, Hepatology Department, Consultative and Diagnostics Department Russian Federation

O. S. Kuz'mina

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Kuz'mina Ol'ga Sergeevna – PhD, Head of the Hepatology Department, Consultative and Diagnostics Department Russian Federation

S. V. Koblov

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Koblov Sergey Vyacheslavovich – Gastroenterologist, Hepatology Department, Consultative and Diagnostics Department Russian Federation

N. V. Voronkova

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Voronkova Natal'ya Vasil'evna – PhD, Specialist in Infectious Diseases, Hepatology Department, Consultative and Diagnostics Department Russian Federation

M. Yu. Petrachenkova

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Petrachenkova Mariya Yur'evna – Gastroenterologist, Hepatology Department, Consultative and Diagnostics Department Russian Federation

A. O. Bueverov

I.M. Sechenov First Moscow State Medical University, Moscow

Email: macievich@gmail.com
Bueverov Aleksey Olegovich – MD, PhD, Professor, Chair of Medical and Social Expert Assessment and Out-Patient Therapy of the Postgraduate Medical Training Faculty, Leading Research Fellow, Department of Research on Innovative Therapy, Research Center Russian Federation

O. V. Uvarova

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Uvarova Ol'ga Vladimirovna – Gastroenterologist, Hepatology Department, Consultative and Diagnostics Department Russian Federation

E. V. Fedosova

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Fedosova Ekaterina Vladimirovna – Physician, Day Care Unit, Consultative and Diagnostics Department Russian Federation

M. N. Trofimova

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Trofimova Marina Nikolaevna – PhD, Specialist in Infectious Diseases, Hepatology Department, Consultative and Diagnostics Department Russian Federation

V. D. Beznosenko

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Beznosenko Valeriy Daniilovich – Specialist in Infectious Diseases, Hepatology Department, Consultative and Diagnostics Department Russian Federation

E. N. Kudryavtseva

Moscow Regional Research and Clinical

Email: macievich@gmail.com
Kudryavtseva Elena Nikolaevna – PhD in Biology, Head of Laboratory of AIDS and Viral Hepatitis Russian Federation

E. M. Kondratenko

Dubna Municipal Hospital, Dubna, Moskovskaya oblast

Email: macievich@gmail.com
Kondratenko Elena Mikhaylovna – Specialist in Infectious Diseases Russian Federation

L. S. Gorbunova

Dmitrov Municipal Hospital, Dmitrovskiy rayon, Moskovskaya oblast

Email: macievich@gmail.com
Gorbunova Lyudmila Stepanovna – Physician, Day Care Unit Russian Federation

I. M. Shilkina

Domodedovo Central Municipal Hospital, Domodedovo, Moskovskaya oblast

Email: macievich@gmail.com
Shilkina Irina Mikhaylovna – Head of Department of Infectious Diseases Russian Federation

T. N. Sheshukova

Out-Patient Clinic of the “Zarya Podmoskov'ya” Hospital, Domodedovo Central Municipal Hospital, s. Rastunovo, gorodskoy okrug Domodedovo, Moskovskaya oblast

Email: macievich@gmail.com
Sheshukova Tat'yana Nikolaevna – Internist, Day Care Unit Russian Federation

I. N. Kovalev

Medical Unit, Domodedovo Central Municipal Hospital, Domodedovo, Moskovskaya oblast

Email: macievich@gmail.com
Kovalev Igor' Nikolaevich – Internist, Day Care Unit Russian Federation

G. V. Sadovskaya

Zhukovskiy Municipal Clinical Hospital, Zhukovskiy, Ramenskiy rayon, Moskovskaya oblast

Email: macievich@gmail.com
Sadovskaya Galina Vladimirovna – Head of Department of Infectious Diseases Russian Federation

N. V. Kosheleva

Zhukovskiy Municipal Clinical Hospital, Zhukovskiy, Ramenskiy rayon, Moskovskaya oblast

Email: macievich@gmail.com
Kosheleva Natal'ya Vladimirovna – Specialist in Infectious Diseases Russian Federation

Yu. Yu. Gumerova

Kolomna Central District Hospital, Kolomna, Moskovskaya oblast

Email: macievich@gmail.com
Gumerova Yulia Yur'evna – Specialist in Infectious Diseases Russian Federation

I. N. Azarova

Krasnogorsk Municipal Hospital No. 1, Krasnogorsk, Moskovskaya oblast

Email: macievich@gmail.com
Azarova Irina Nikolaevna – Head of Day Care Unit Russian Federation

S. V. Ivannikova

Lyubertsy District Hospital No. 2, Lyubertsy, Moskovskaya oblast

Email: macievich@gmail.com
Ivannikova Svetlana Vladimirovna – Head of Day Care Unit Russian Federation

E. N. Cherenkova

Mytishchi Town Clinical Hospital, Mytishchi, Moskovskaya oblast'

Email: macievich@gmail.com
Cherenkova Ekaterina Nikolaevna – Gastroenterologist Russian Federation

N. A. Gorshilina

Odintsovo Central Hospital, Odintsovo, Moskovskaya oblast

Email: macievich@gmail.com
Gorshilina Nadezhda Andreevna – Head of Department of Internal Medicine Russian Federation

M. L. Samsonyan

Odintsovo Central Hospital, Odintsovo, Moskovskaya oblast

Email: macievich@gmail.com
Samsonyan Marina Leonidovna – Internist Russian Federation

V. A. Sinitsyna

Odintsovo Central Hospital, Odintsovo, Moskovskaya oblast

Email: macievich@gmail.com
Sinitsyna Viktoriya Aleksandrovna – Internist Russian Federation

S. I. Kiyan

Odintsovo Central Hospital, Odintsovo, Moskovskaya oblast

Email: macievich@gmail.com
Kiyan Svetlana Il'inichna – Head of Department of Infectious Diseases, Specialist in Infectious Diseases Russian Federation

O. A. Kudrya

Medical Center “New Medtechnologies, Ramenskoe, Moskovskaya oblast

Email: macievich@gmail.com
Kudrya Ol'ga Anatol'evna – Head of Department of Infectious Diseases Russian Federation

G. G. Chernyavskaya

Khimki Central Clinical Hospital, Khimki, Moskovskaya oblast

Email: macievich@gmail.com
Chernyavskaya Galina Gur'evna – Head of Day Care Unit Russian Federation

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Copyright (c) 2016 Bogomolov P.O., Matsievich M.V., Kokina K.Y., Kuz'mina O.S., Koblov S.V., Voronkova N.V., Petrachenkova M.Y., Bueverov A.O., Uvarova O.V., Fedosova E.V., Trofimova M.N., Beznosenko V.D., Kudryavtseva E.N., Kondratenko E.M., Gorbunova L.S., Shilkina I.M., Sheshukova T.N., Kovalev I.N., Sadovskaya G.V., Kosheleva N.V., Gumerova Y.Y., Azarova I.N., Ivannikova S.V., Cherenkova E.N., Gorshilina N.A., Samsonyan M.L., Sinitsyna V.A., Kiyan S.I., Kudrya O.A., Chernyavskaya G.G.

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