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.

Elihu Aranday-Cortes,Jonathan K Ball,Matthew E Cramp,Lily Tong,William L Irving,Kosh Agarwal,C Patrick Mcclure,Christopher Davis,Benjamin Stone,Ana Da Silva Filipe,Kazeem Adeboyejo,Emma C Thomson,David Mutimer,Vattipally Sreenu,John Mclauchlan

doi:10.1093/infdis/jiab110

Abstract

BackgroundChronic 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.MethodsWe 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.ResultsFull-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.ConclusionsDAA 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.

Highlights

Background Chronic HCV infection affects71 million individuals, mostly residing in low- and middleincome countries (LMICs)
Most subtypes of HCV s genotypes 4, 5 and 6 have been largely neglected, yet they represent about 15% of chronic HCV infections u [7]. n We recently reported a substantial gap in our knowledge of HCV genomic sequences circulating in LMICs a across large geographic areas [8]
We and others have identified HCV genotype(gt)1 and gt4 M subtypes in infected patients of African origin that do not respond to Direct-acting antivirals (DAA) therapy as well as subtypes d typically transmitted in high-income countries (HICs); treatment failure using a Sofosbuvir/Ledipasvir (SOF/LDV) combination has te been evident with HCV subtypes gt1l [9, 10] and gt4r [10,11,12,13,14]

Summary

Introduction

Background Chronic HCV infection affects71 million individuals, mostly residing in low- and middleincome countries (LMICs). We and others have identified HCV genotype(gt)1 and gt4 M subtypes in infected patients of African origin that do not respond to DAA therapy as well as subtypes d typically transmitted in HICs; treatment failure using a Sofosbuvir/Ledipasvir (SOF/LDV) combination has te been evident with HCV subtypes gt1l [9, 10] and gt4r [10,11,12,13,14].

Results

Conclusion