Abstract
BackgroundIn-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data.ResultsOur results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs.ConclusionsThe patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies.
Highlights
In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning
The Q80K variant was detected in 23.9% of all strains, and a somewhat lower prevalence of 19.3% was observed for Western Europe
Multiple independent introductions of HCV subtype 1a (HCV1a) and Q80K in Italy Bayesian phylogeographic methods were used to determine when and from where HCV1a strains were introduced into Italy
Summary
In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Hepatitis C virus (HCV) infected patients are nowadays treated with interferon-free regimens containing one or more antivirals that directly target virus proteins 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]. Baseline drug resistance testing is only recommended in well-defined cases such as the combination of NS3/4A protease inhibitor (PI) simeprevir with NS5B polymerase inhibitor sofosbuvir. This regimen is associated with reduced viral cure rates in HCV subtype 1a (HCV1a) cirrhotic patients who carry the naturally occurring, highly prevalent RAV Q80K [3,4,5,6]. Given the increased interest into the natural prevalence of several other RAVs, located in NS5A [4, 7], insights into the patterns of HCV1a spread may be interesting for these variants as well
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