High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study

ABSTRACT

Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment.

Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point.

Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis.

Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.

KEYWORDS:

• Chronic HCV Genotype 4
• Direct acting antivirals failure
• sofosbuvir
• daclatasvir
• ribavirin
• virologic response
• safety
• interval

Author contributions

All authors supervised patients’ treatment and follow up. Mohamed Abd Allah collected patient data. Wafaa ElAkel and Heba Omar performed statistical analysis. Samar Darwesh, Maissa El Raziky, Wafaa El Akel, Heba Omar drafted the manuscript, Imam Waked revised and edited the manuscript. Gamal Esmat and Imam Waked are responsible for the overall content as guarantor. All authors revised and approved the final version.

Declaration of interest

W. Doss has served as an investigator and speaker for Gilead Sciences. G. Esmat has served as an investigator, speaker or advisory board member for Abbvie, Gilead Sciences, Marcyrl, Pharco and Roche. I. Waked has served as an investigator, speaker or advisory board member for Abbvie, Eva Pharma, Gilead Sciences, Janssen, Marcyrl, Onxio, Pharco and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This paper was not funded.