Intra-host evolutionary dynamics of the hepatitis C virus among people who inject drugs

Abstract

Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve existing surveillance data and help guide treatment. While intra-host viral diversity quantifications such as Shannon entropy have previously been utilized for estimating duration of infection, these studies characterize the viral population from only a relatively short segment of the HCV genome. In this study intra-host diversities were examined across the HCV genome in order to identify the region most reflective of time and the degree to which these estimates are influenced by high-risk activities including those associated with HCV acquisition. Shannon diversities were calculated for all regions of HCV from 78 longitudinally sampled individuals with known seroconversion timeframes. While the region of the HCV genome most accurately reflecting time resided within the NS3 gene, the gene region with the highest capacity to differentiate acute from chronic infections was identified within the NS5b region. Multivariate models predicting duration of infection from viral diversity significantly improved upon incorporation of variables associated with recent public, unsupervised drug use. These results could assist the development of strategic population treatment guidelines for high-risk individuals infected with HCV and offer insights into variables associated with a likelihood of transmission.

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

“…We have recently reported clock-like characteristics of the HCV genome in which intra-host viral genetic diversity increases over time. 27 People with a longer duration of infection may have increased viral diversity shaped by immune selection, resulting in polymorphisms with increased fitness, including RASs and other compensatory substitutions. Indeed, a high prevalence of baseline NS5A RASs was reported in a cohort of HIV-HCV patients with advanced fibrosis and cirrhosis and older mono-infected patients in Poland.…”