title: Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy.
abstract: In-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.
  
  
  
  Our 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.
  
  
  
  The 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.
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium. lize.cuypers@kuleuven.be.
authors.forename: Lize
authors.initials: L
authors.lastname: Cuypers
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Vrancken
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani-IRCCS, Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fabeni
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium.|Department of Health Sciences, Institute of Microbiology, School of Medicine, University of "Magna Graecia", Viale Europa, Germaneto, 88100, Catanzaro, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Marascio
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cento
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Velia Chiara
authors.initials: VC
authors.lastname: Di Maio
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Aragri
authors.affiliation: Global Health and Tropical Medicine, GHTM, Institute for Hygiene and Tropical Medicine, IHMT, University Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008, Lisbon, Portugal.|Molecular Biology and Immunology Department, Fundación Instituto de Immunología de Colombia (FIDIC), Basic Sciences Department, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Andrea Clemencia
authors.initials: AC
authors.lastname: Pineda-Peña
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium.
authors.forename: Yoeri
authors.initials: Y
authors.lastname: Schrooten
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
authors.affiliation: Luciad, Computer Software, Gaston Geenslaan 11, 3001, Heverlee, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Balog
authors.affiliation: Department of Health Sciences, Institute of Microbiology, School of Medicine, University of "Magna Graecia", Viale Europa, Germaneto, 88100, Catanzaro, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Focà
authors.affiliation: Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, School of Medicine, University of "Magna Graecia", Viale Europa, Germaneto, 88100, Catanzaro, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.affiliation: KU Leuven - University of Leuven, Department of Clinical and Experimental Medicine, Hepatology, Leuven, Belgium.|University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Herestraat 49 - box 1040, 3000, Leuven, Belgium.|Global Health and Tropical Medicine, GHTM, Institute for Hygiene and Tropical Medicine, IHMT, University Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008, Lisbon, Portugal.
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001499:Bayes Theorem; D024882:Drug Resistance, Viral; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D000069616:Simeprevir / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D000069616:Simeprevir
keywords: Europe; HCV; HCV1a; Italy; Phylogeography; Public health policy; Q80K; US