TY - JOUR
T1 - Deep-sequencing study of HCV g4a resistanceassociated substitutions in egyptian patients failing DAA treatment
AU - Amer, Fatma
AU - Yousif, Monkez M.
AU - Hammad, Noha M.
AU - Garcia-Cehic, Damir
AU - Gregori, Josep
AU - Rando-Segura, Ariadna
AU - Nieto-Aponte, Leonardo
AU - Esteban, Juan Ignacio
AU - Rodriguez-Frias, Francisco
AU - Quer, Josep
N1 - Funding Information:
This study was supported by the Spanish Ministry of Health, Consumer Affairs, and Social Welfare, grant name: Plan Estratégico 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 Investigación en Red de Enfermedades Hepaticas y Digestivas), which is funded by Instituto de Salud Carlos III and Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number, IDI-20151125. The authors thank Celine Cavallo for English language support and helpful editing suggestions.
Publisher Copyright:
© 2019 Amer et al.
PY - 2019/9/10
Y1 - 2019/9/10
N2 - Purpose: 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.
AB - Purpose: 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.
KW - Resistance-associated substitutions
KW - RAS
KW - Subtype 4a
KW - Treatment failure
KW - Egypt
KW - Direct acting antivirals
KW - DAA
KW - Resistance-associated substitutions
KW - RAS
KW - Subtype 4a
KW - Treatment failure
KW - Egypt
KW - Direct acting antivirals
KW - DAA
KW - Resistance-associated substitutions
KW - RAS
KW - Subtype 4a
KW - Treatment failure
KW - Egypt
KW - Direct acting antivirals
KW - DAA
UR - http://www.scopus.com/inward/record.url?scp=85073332101&partnerID=8YFLogxK
U2 - 10.2147/IDR.S214735
DO - 10.2147/IDR.S214735
M3 - Article
AN - SCOPUS:85073332101
SN - 1178-6973
VL - 12
SP - 2799
EP - 2807
JO - Infection and Drug Resistance
JF - Infection and Drug Resistance
ER -