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- Title
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.
- Authors
Aranday-Cortes, Elihu; McClure, C Patrick; Davis, Christopher; Irving, William L; Adeboyejo, Kazeem; Tong, Lily; Filipe, Ana da Silva; Sreenu, Vattipally; Agarwal, Kosh; Mutimer, David; Stone, Benjamin; Cramp, Matthew E; Thomson, Emma C; Ball, Jonathan K; McLauchlan, John; da Silva Filipe, Ana
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
AFRICA; UNITED Kingdom; HEPATITIS C virus; CHRONIC hepatitis C; GENOTYPES; ANTIVIRAL agents; HIGH-income countries; COMBINATION drug therapy; HETEROCYCLIC compounds; HEPATITIS viruses; HYDROCARBONS; REOPERATION; RESEARCH funding; DISEASE complications
- Publication
Journal of Infectious Diseases, 2022, Vol 226, Issue 6, p995
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab110