Saturday, November 3, 2018

New highly diverse hepatitis C strains detected in sub‐Saharan Africa have unknown susceptibility to direct‐acting antiviral treatments

New highly diverse hepatitis C strains detected in sub‐Saharan Africa have unknown susceptibility to direct‐acting antiviral treatments 
Chris Davis George S. Mgomella Ana da Silva Filipe Eric H. Frost Genevieve Giroux Joseph Hughes Catherine Hogan Pontiano Kaleebu Gershim Asiki John McLauchlan Marc Niebel

 First published: 02 November 2018 

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Accepted manuscript online: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record.

Background and rationale for the study
The global plan to eradicate hepatitis C (HCV) led by the World Health Organisation (WHO) outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC), to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterise genetic diversity of the virus. Using next generation (NGS) and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa.

Main results
7751 Ugandan patients were initially screened for HCV and 20 PCR positive samples obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotypes (g) 4k, 4p, 4q and 4s and a new unassigned genotype 7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full ORF sequence). These g4 and 7 strains contain NS3 and NS5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients.

While HCV prevalence and genotypes have been well characterised in patients in well‐resourced countries, clinical trials are urgently required in SSA where highly diverse g4 and 7 strains circulate.

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