HIV co‐infection is associated with increased transmission risk in patients with chronic hepatitis C virus

Molecular epidemiological analysis of viral pathogens can identify factors associated with increased transmission risk. We investigated the frequency of genetic clustering in a large data set of NS34A, NS5A, and NS5B viral sequences from patients with chronic hepatitis C virus (HCV). Within a subset of patients with longitudinal samples, Receiver Operator Characteristic (ROC) analysis was applied which identified a threshold of 0.02 substitutions/site as most appropriate for clustering. From the 7457 patients with chronic HCV infection included in this analysis, we inferred 256 clusters comprising 541 patients (7.3%). We found that HCV/HIV co-infection, young age, and high HCV viral load were all associated with increased clustering frequency, an indicator of increased transmission risk. In light of previous work on HCV/HIV co-infection in acute HCV cohorts, our results suggest that patients with HCV/HIV co-infection may disproportionately be the source of new HCV infections and treatment efforts should be geared towards viral elimination in this vulnerable population

HIV co‐infection is associated with increased transmission risk in patients with chronic hepatitis C virus

Molecular epidemiological analysis of viral pathogens can identify factors associated with increased transmission risk. We investigated the frequency of genetic clustering in a large data set of NS34A, NS5A, and NS5B viral sequences from patients with chronic hepatitis C virus (HCV). Within a subset of patients with longitudinal samples, Receiver Operator Characteristic (ROC) analysis was applied which identified a threshold of 0.02 substitutions/site as most appropriate for clustering. From the 7457 patients with chronic HCV infection included in this analysis, we inferred 256 clusters comprising 541 patients (7.3%). We found that HCV/HIV co-infection, young age, and high HCV viral load were all associated with increased clustering frequency, an indicator of increased transmission risk. In light of previous work on HCV/HIV co-infection in acute HCV cohorts, our results suggest that patients with HCV/HIV co-infection may disproportionately be the source of new HCV infections and treatment efforts should be geared towards viral elimination in this vulnerable population

Lethal mutagenesis of hepatitis C virus induced by favipiravir

Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagen. Here we show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during its replication in human hepatoma cells. T-705 leads to an excess of G!A and C!U transitions in the mutant spectrum of preextinction HCV populations. Infectivity decreased significantly in the presence of concentrations of T-705 which are 2- to 8-fold lower than its cytotoxic concentration 50 (CC50). Passaging the virus five times in the presence of 400 μM T-705 resulted in virus extinction. Since T-705 has undergone advanced clinical trials for approval for human use, the results open a new approach based on lethal mutagenesis to treat hepatitis C virus infections. If proven effective for HCV in vivo, this new anti-HCV agent may be useful in patient groups that fail current therapeutic regimens.BFU-2011-23604, SAF2014-52400-R, S2013/ABI-2906 (PLATESA from Comunidad de Madrid/FEDER) and Fundación R. Areces. The work in Barcelona was funded by Instituto de Salud Carlos III, grants PI13-00456 and PI15-00829, cofinanced by the European Regional Development Fund (ERDF).Peer Reviewe