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Original article
Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt
  1. Gamal Shiha1,2,
  2. Gamal Esmat3,
  3. Mohamed Hassany4,
  4. Reham Soliman2,5,
  5. Mohamed Elbasiony1,2,
  6. Rabab Fouad3,
  7. Aisha Elsharkawy3,
  8. Radi Hammad4,
  9. Wael Abdel-Razek6,
  10. Talaat Zakareya6,
  11. Kathryn Kersey7,
  12. Benedetta Massetto7,
  13. Anu Osinusi7,
  14. Sophia Lu7,
  15. Diana M Brainard7,
  16. John G McHutchison7,
  17. Imam Waked6,
  18. Wahid Doss4
  1. 1 Internal Medicine Department, Mansoura University, Mansoura, Egypt
  2. 2 Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
  3. 3 Endemic Medicine and Hepatogastroenterology Department, Faulty of Medicine, Cairo University, Cairo, Egypt
  4. 4 National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
  5. 5 Tropical Medicine, Port Said University, Port Said, Egypt
  6. 6 National Liver Institute–Menoufia University, Shebeen El Kom, Egypt
  7. 7 Gilead Sciences, Foster City, California, USA
  1. Correspondence to Professor Gamal Shiha, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Dakahlia 35516, Egypt; g_shiha{at}hotmail.com

Abstract

Objective We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens.

Design In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12).

Results We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin.

Conclusion Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir.

Trial registration number NCT02487030.

  • chronic hepatitis
  • genotype
  • cirrhosis

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Footnotes

  • Contributors All authors had access to the data and approved the final version of the manuscript.

  • Funding This study was funded by Gilead Sciences Inc. (Foster City, California, USA).

  • Competing interests GS has served as a principal investigator for AbbVie and Gilead. GE has served as a principal investigator for AbbVie, Gilead, BMS and Pharco Pharmaceuticals, and has served as a speaker for Gilead and BMS, and has served on advisory boards for Gilead and MSD. MH has served as an investigator for AbbVie, Janssen and Gilead, and has served as a speaker for AbbVie. RS has served as an investigator for AbbVie and Gilead. ME has served as an investigator for Gilead. RF has served as an investigator for Gilead, Abbie and Pharco Pharmaceuticals. AE has served as an investigator for Gilead, Abbvie and Janssen. RH declares no conflicts of interest. WA-R has served as a co-investigator for Gilead, Janssen and AbbVie. TZ has served as a co-investigator for Janssen and AbbVie. IW has served as an investigator, speaker and on advisory boards for AbbVie, Eva Pharma, Gilead, Janssen, Marcyrl, Onxio, Pharco and Roche. WD has served as an investigator for AbbVie, Janssen and Gilead. The following coauthors are employees of and hold stock interest in Gilead Sciences: KK, BM, AO, SL, DMB and JGMcH.

  • Patient consent Obtained.

  • Ethics approval The protocol was approved by an independent ethics committee or an institutional review board according to site-specific regulations.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All authors had access to the data.

  • Correction notice This article has been corrected since it published Online First. Table 1 and affiliation 3 have been updated.

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