Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

Abstract

Around 70 to 100 million people are chronically infected with HCV worldwide. HCV antiviral drug development has revolutionised the treatment of HCV, with several direct-acting antiviral agents offering patients the chance of cure after only 8-12 weeks of treatment. Drug development was initially focussed on HCV genotype 1 (GT1) infection, since this was the most prevalent worldwide, although clinical trials included all genotypes prevalent in the US and Europe. Because the earliest in vitro assays utilised the GT1b and 2 replicons, the initial classes of direct-acting antivirals (protease inhibitors, non-nucleotide polymerase inhibitors) were GT1-specific, albeit they had an effect on other less prevalent genotypes. Epidemiological data has shown the regional importance of other HCV genotypes. More than 50% of all HCV infections around the globe are not with GT1. The prevalence of HCV genotype 4 (GT4), 5 (GT5), and 6 (GT6) is increasing in North America and Europe due to migration from the Middle East, Africa and South-East Asia. With the successful development of the multi and pan-genotypic non-structural protein 5A inhibitors, second generation protease inhibitors and nucleotide non-structural protein 5B inhibitors comes a unique opportunity to achieve global HCV elimination. The goal of this review is to summarise the available information pertaining to GT4, GT5 and GT6, with a specific focus on direct-acting antiviral agents.

Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

“…This is particularly true for the treatment of HCV genotypes 4, 5, and 6, which were underrepresented in most clinical trials but are highly prevalent in many middle-and low-income countries across the globe. 71 GLE/PIB is a once-daily regimen for the treatment of all HCV genotypes, with an 8-week treatment duration in most non-cirrhotic patients. However, the most distinctive feature of this regimen is the high antiviral activity in HCV genotype 1a, even in patients with prior PEG-IFN failure and those with cirrhosis.…”

Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study

“…Approximately 13%‐15% of global hepatitis C virus (HCV) infections are caused by HCV genotype (GT) 4 . HCV GT4 infection is prevalent in countries of sub‐Saharan Africa and the Middle East, particularly Egypt, where >90% of HCV‐infected individuals have GT4 infection .…”

An educate, test and treat model towards elimination of hepatitis C infection in Egypt: Feasibility and effectiveness in 73 villages

“…This may include access to a point of care test for HCV viraemia that can be used easily in the field, such as Gene Expert for more remote areas, as well as adoption of simple validated blood-based non-invasive tests for staging of fibrosis, such as the APRI score 23 that could replace the more expensive FibroScan, and use of other pan-genotypic regimens with shorter treatment duration and without ribavirin. 39 We also believe that this village-based HCV screening initiative represents an excellent opportunity for integration with more comprehensive noncommunicable disease screening, alongside blood pressure, diabetes and BMI measurements. Almost one-quarter of our 15,892 HCV RNA-positive study population had > − 1 significant comorbidities such as diabetes and/or hypertension/ischaemic heart disease, and 54.7% were considered obese based on a BMI > − 30 kg/m 2 .…”