Deep-sequencing study of HCV G4a resistance-associated substitutions in Egyptian patients failing DAA treatment

Resistance-associated substitutions; RAS; Subtype 4aSustituciones asociadas a la resistencia; RAS; Subtipo 4aSubstitucions associades a la resistència; RAS; Subtipus 4aPurpose: To study resistance-associated substitutions using next-generation sequencing in Egyptian hepatitis C virus-infected patients failing direct-acting antiviral treatment. Methods: The current study describes three cases of treatment failure in patients referred to Zagazig Viral Hepatitis Treatment Center (ZVHTC), Sharkia Governorate, Egypt. RAS were identified and characterized using deep sequencing. The first patient had breakthrough while receiving a daclatasvir (DCV)+sofosbuvir (SOF) regimen, patient 2 relapsed after treatment with DCV+SOF+ribavirin (RBV), and patient 3 relapsed after DCV+SOF therapy. A serum sample was collected from each patient at failure and sent to Vall d’Hebron Research Institute at Hospital Universitari Vall d’Hebron in Barcelona (Spain) for deep-sequencing study to identify and characterize the RAS present in the samples. Results: The following were identified: L28M, L30S and L28M+L30S in patient 1, L30R in patient 2, and R155C, D168E, L28M, L30H, L30S, L28M+L30H, and L28M+L30S in patient 3. Conclusion: To the best of our knowledge, this is the first report from Egypt of patients failing DAA-based therapy, describing the associated RAS. This information will be of help to understand the natural history of HCV in Egyptian patients and guide the proper choice of retreatment protocols.This study was supported by the Spanish Ministry of Health, Consumer Affairs, and Social Welfare, grant name: Plan Estrategico Nacional contra la Hepatitis C. This study was also funded by Instituto de Salud Carlos III, PI15/00856 and PI16/00337, cofinanced by CIBERehd (Consorcio Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas), which is funded by Instituto de Salud Carlos III and Centro para el Desarrollo Tecnologico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number, IDI-2015112