Digestive Diseases and Sciences

, Volume 63, Issue 5, pp 1341–1347 | Cite as

Retreatment Efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/Ritonavir + Ribavirin for Hepatitis C Virus Genotype 4 Patients

  • Adel Abdel-Moneim
  • Alaa Aboud
  • Mohamed Abdel-Gabbar
  • Mohamed Zanaty
  • Mohamed Ramadan
Original Article
  • 127 Downloads

Abstract

Background

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection.

Aims

To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens.

Methods

A total of 113 treatment-experienced patients were allocated for the completion of their treatment period. The enrolled patients were treated orally with SOF plus a fixed dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients’ tolerability. The primary end point was a sustained virological response (HCV RNA < 15 IU/mL), observed 12 weeks after the end of the treatment (SVR12).

Results

Among all patients, the treatment-experienced patients with SOF plus OBV/PTV/r + RBV had a higher SVR12 rate (97%; 109/113). Further, SVR12 was achieved by 98% (81/83) of non-cirrhotic patients and 93% (28/30) of cirrhotic patients. Additionally, the most common adverse events reported included fatigue, headache, insomnia, nausea, and dyspnea.

Conclusions

The recent multi-targeted regimen of SOF plus OBV/PTV/r + RBV was well tolerated and achieved excellent SVR rates among retreatment-experienced Egyptian patients with prior DAA treatments failure, thus providing an alternative regimen for the retreatment of difficult-to-cure HCV GT4 patients.

Keywords

Egyptian patients Sofosbuvir Ombitasvir Paritaprevir Ritonavir Ribavirin 

Notes

Acknowledgments

The authors acknowledge with grateful appreciation to the staff member of the National Treatment Centers in Beni-Suef, Egypt. We thank the patients and their families, as well as Mss/Asmaa Mahmoud Gaber for her generous help in figures preparation.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Sievert W, Altraif I, Razavi HA, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 2011;31:61–80.CrossRefPubMedGoogle Scholar
  2. 2.
    Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017;2:161–176.CrossRefGoogle Scholar
  3. 3.
    Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52:889–900.CrossRefPubMedGoogle Scholar
  4. 4.
    Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:S45–S57.CrossRefPubMedGoogle Scholar
  5. 5.
    European Association for Study of Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66:153–194.CrossRefGoogle Scholar
  6. 6.
    Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–1887.CrossRefPubMedGoogle Scholar
  7. 7.
    DeGoey DA, Randolph JT, Liu D, et al. Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014;57:2047–2057.CrossRefPubMedGoogle Scholar
  8. 8.
    Polepally AR, Badri PS, Eckert D, et al. Effects of mild and moderate renal impairment on ombitasvir, paritaprevir, ritonavir, dasabuvir, and ribavirin pharmacokinetics in patients with chronic HCV infection. Eur J Drug Metab Pharmacokinet. 2017;42:333–339.CrossRefPubMedGoogle Scholar
  9. 9.
    Pawlotsky JM, Hepatitis C. Virus Resistance to Direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016;151:70–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Soriano V, Fernandez-Montero JV, de Mendoza C, et al. Treatment of hepatitis C with new fixed dose combinations. Expert Opin Pharmacother. 2017;18:1235–1242.CrossRefPubMedGoogle Scholar
  11. 11.
    Keating GM. Ombitasvir/Paritaprevir/Ritonavir: A review in chronic HCV genotype 4 infection. Drugs. 2016;76:1203–1211.CrossRefPubMedGoogle Scholar
  12. 12.
    Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org; 2016. Accessed 24 June 2016.
  13. 13.
    Voaklander R, Jacobson IM. Sofosbuvir, Velpatasvir and Voxilaprevir combination for the treatment of hepatitis C. Expert Rev Gastroenterol Hepatol. 2017;11:789–795.CrossRefPubMedGoogle Scholar
  14. 14.
    Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology. 2005;43:1317–1325.CrossRefGoogle Scholar
  15. 15.
    Friborg J, Zhou N, Han Z, et al. In vitro assessment of retreatment options for patients with hepatitis C virus genotype 1b infection resistant to daclatasvir plus asunaprevir. Infect Dis Ther. 2015;4:137–144.CrossRefGoogle Scholar
  16. 16.
    Tamori A, Enomoto M, Kawada N. Recent advances in antiviral therapy for chronic hepatitis C. Mediators Inflamm. 2016;.  https://doi.org/10.1155/2016/6841628.Google Scholar
  17. 17.
    Buti M, Esteban R. Management of direct antiviral agent failures. Clin Mol Hepatol. 2016;22:432–438.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Shafran SD, Shaw D, Charafeddine M, et al. Efficacy and safety results of patients with HCV genotype 2 or 3 infection treated with ombitasvir/paritaprevir/ritonavir and sofosbuvir with or without ribavirin (QUARTZ II-III). J Viral Hepat. 2017;.  https://doi.org/10.1111/jvh.12782.PubMedGoogle Scholar
  19. 19.
    Flisiak R, Janczewska E, Wawrzynowicz-Syczewska M, et al. Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study. Aliment Pharmacol Ther. 2016;44:946–956.CrossRefPubMedGoogle Scholar
  20. 20.
    Wedemeyer H, Craxí E, Zuckerman A, et al. Real world effectiveness of ombitasvir, paritaprevir, ritonavir, dasabuvir, ribavirin in patients with hepatitis C virus genotype 1 or 4 infection A meta-analysis. J Viral Hepat. 2017;24:936–943.CrossRefPubMedGoogle Scholar
  21. 21.
    U.S. Food and Drug Administration. FDA approves Vosevi for Hepatitis C. July 18, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567467.htm.
  22. 22.
  23. 23.
    Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376:2134–2146.CrossRefPubMedGoogle Scholar
  24. 24.
    Zeuzem S, Flamm S, Tong M, et al. A randomized, controlled, phase 3 trial of sofosbuvir velpatasvir-voxilaprevir or sofosbuvir-velpatasvir for 12 weeks in direct-acting antiviral-experienced patients with genotype 1–6 HCV infection: the POLARIS-4 study. American Association for the Study of Liver Disease (AASLD), November 2016. Boston, USA. http://www.natap.org/2016/AASLD/AASLD_18.htm.
  25. 25.
    Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147:359–365.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular Physiology Division, Faculty of ScienceBeni-Suef UniversityBeni SuefEgypt
  2. 2.Tropical Medicine Department, Faculty of MedicineBeni-Suef UniversityBeni SuefEgypt
  3. 3.Biochemistry Division, Chemistry Department, Faculty of ScienceBeni-Suef UniversityBeni SuefEgypt
  4. 4.Biotechnology Department, Postgraduate Studies for Advanced ScienceBeni-Suef UniversityBeni SuefEgypt

Personalised recommendations