Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time

Abstract

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.

Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy

“…These new direct-acting antivirals (DAAs) have a superb efficacy and, when combined, can clear the virus in more than 95% of the treated population, irrespective of the HCV genotype [1]. For most DAAs no clear association of particular naturally occurring resistance-associated variants (RAVs) with clinical outcome has been identified [2].…”

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

“…In the past two decades, the only standard treatment for patients with HCV infection is peg-interferon plus ribavirin (PegIFN/RBV) in 24 to 72 weeks, but only a limited proportion of patients can achieve a sustained virological response (SVR), defined as HCV RNA continues to be undetectable in serum at 12 weeks after completing treatment. What is worse, the interferon-based agent can cause many adverse effects in more than 10% of patients during and after the treatment [4], such as depression, cytoreduction and hemolytic anemia [5]. Fortunately, as DAA drugs have been developed rapidly and used in the clinical application, the cure rate of chronic hepatitis C has a revolutionary improvement even in patients with liver cirrhosis, and the efficiency persists to rise from the first generation to the third generation DAA drugs [6].…”

Exploring resistance pathways for first-generation NS3/4A protease inhibitors boceprevir and telaprevir using Bayesian network learning

“…Since HCV manifests as seven genotypes (GTs) and N50 subtypes (Smith et al, 2014), developing a pan-genotypic drug proved to be challenging. However, concerted efforts led to the current generation of anti-HCV drugs with dramatically improved treatment success rates (Zeuzem et al, 2011;Cuypers et al, 2016b). As a result, highly efficient direct-acting antivirals (DAAs) were approved for HCV treatment starting from 2011, including NS3/4A protease inhibitors (PIs), NS5A inhibitors and NS5B polymerase inhibitors.…”

“…The most recent PIs feature a higher genetic barrier to resistance, as well as broader antiviral activity, e.g. paritaprevir and grazoprevir (Andreone et al, 2014;Cuypers et al, 2016b;Zeuzem et al, 2015a).…”