Resistance to protease inhibitors and efficiency of antiviral therapy in patients with chronic hepatitis C


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Abstract

Aim. To clarify the role of virus resistance in the efficiency of antiviral therapy with protease inhibitors (PIs) chronic hepatitis C (CHC) patients, with moderate sensitivity to interferon-α. Subjects and methods. Eight Caucasian patients (4 men and 4 women) aged 21 to 65 years (median 52.5 years) with genotype 1b hepatitis C virus (HCV) infection were included in the study. Two patients were diagnosed with liver cirrhosis; 4 had been ineffectively treated with peginterferon in combination with ribavirin. None of the patients had obesity and/or insulin resistance. All the 8 patients received triple therapy with PIs (boceprevir (n=3), telaprevir (n=4), and simeprevir (n=1)) and as a result failed to achieve a sustained virologic response. All the participants were studied to identify mutations in HCV NS3/4A region. Results. Five of the 8 patients were found to have mutations in HCV NS3/4A region (substantially reducing drug susceptibility in 3 cases). Conclusion. In CHC patients who are moderately sensitive to interferon-α and receive therapy with PIs, resistance to the latter is critically important for the efficiency of therapy and the timely identification of resistance mutations can contribute to the choice of an optimal treatment policy.

References

  1. Рекомендации по диагностике и лечению взрослых больных гепатитом С. Москва: Новые печатные технологии 2014. Доступно по: http://www.rsls.ru/ru/for-specialists/recommendations/ 20-recomend-3. Ссылка активна на 09.06.2015.
  2. Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. Journal of Hepatology [Internet]. Elsevier BV; 2011;55(1):192-206. Available at: http://dx.doi.org/10.1016/j.jhep.2011.01.011
  3. Poveda E, Soriano V. Drug resistance testing in hepatitis C therapy. Future Virology [Internet]. Future Medicine Ltd.; 2012;7(3):309-321. Available at: http://dx.doi.org/10.2217/fvl. 12.13
  4. Wyles DL. Antiviral Resistance and the Future Landscape of Hepatitis C Virus Infection Therapy. Journal of Infectious Diseases [Internet]. Oxford University Press (OUP); 2013;207(suppl 1):S33-S39. Available at: http://dx.doi.org/10.1093/infdis/jis761
  5. Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM,Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK; SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomized, multicentre phase 2 trial. The Lancet [Internet]. Elsevier BV; 2010;376(9742):705-716. Available at: http://dx.doi.org/10.1016/s0140-6736(10)60934-8
  6. Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourlière M, Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T,Kwong A, Kauffman RS, Alam J, Pawlotsky JM, Zeuzem S; PROVE2 Study Team. Telaprevir and Peginterferon with or without Ribavirin for Chronic HCV Infection. N Engl J Med. [Internet]. New England Journal of Medicine (NEJM/MMS). 2009;360(18):1839-1850. Available at: http://dx.doi.org/10.1056/nejmoa0807650
  7. Kieffer TL, Bartels DJ, Sullivan J, Adiwijaya BS, Zhang EZ, Tigges A, Dorrian J, Spanks J, De Meyer S, Picchio G, Adda N, Kwong AD. Clinical virology results from telaprevir Phase 3 study ADVANCE. Hepatology. 2010;52(Suppl.):879A. doi: 10.1002/hep.23993.
  8. Pawlotsky J-M. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology [Internet]. Wiley-Blackwell; 2011;53(5):1742-1751. Available at: http://dx.doi.org/10.1002/hep.24262
  9. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for Untreated Chronic HCV Genotype 1 Infection. N Engl J Med [Internet]. New England Journal of Medicine (NEJM/MMS). 2011;364(13):1195-1206. Available at: http://dx.doi.org/10.1056/nejmoa1010494

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