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Real-world outcomes of direct-acting antiviral treatment and retreatment in United Kingdom-based patients infected with hepatitis C virus genotypes/subtypes endemic in Africa
McClure, C. Patrick Irving, William L. Adeboyejo, Kazeem Ball, Jonathan K.
McClure, C. Patrick
Irving, William L.
Adeboyejo, Kazeem
Ball, Jonathan K.
Abstract
BACKGROUND: Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate. METHODS: We studied United Kingdom-resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients. RESULTS: Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma. CONCLUSIONS: DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option. Copyright © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
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Date
2022
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Aranday-Cortes, E., McClure, C.P., Davis, C., Irving, W.L., Adeboyejo, K., Tong, L., da Silva Filipe, A., Sreenu, V., Agarwal, K., Mutimer, D., Stone, B., Cramp, M.E., Thomson, E.C., Ball, J.K. and McLauchlan, J. (2022) 'Real-world outcomes of direct-acting antiviral treatment and retreatment in United Kingdom-based patients infected with hepatitis C virus genotypes/subtypes endemic in Africa', Journal of Infectious Diseases, 226(6), pp. 995-1004. doi: 10.1093/infdis/jiab110 https://doi.org/10.1093/infdis/jiab110.