title: Transmission of hepatitis C virus infection among younger and older people who inject drugs in Vancouver, Canada.
abstract: Understanding HCV transmission among people who inject drugs (PWID) is important for designing prevention strategies. This study investigated whether HCV infection among younger injectors occurs from few or many transmission events from older injectors to younger injectors among PWID in Vancouver, Canada.
  
  
  
  HCV antibody positive participants at enrolment or follow-up (1996-2012) were tested for HCV RNA and sequenced (Core-E2). Time-stamped phylogenetic trees were inferred using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Association of age with phylogeny was tested using statistics implemented in the software Bayesian Tip Significance (BaTS) testing. Factors associated with clustering (maximum cluster age: five years) were identified using logistic regression.
  
  
  
  Among 699 participants with HCV subtype 1a, 1b, 2b and 3a infection (26% female, 24% HIV+): 21% were younger (<27years), and 10% had recent HCV seroconversion. When inferred cluster age was limited to <5years, 15% (n=108) were in clusters/pairs. Although a moderate degree of segregation was observed between younger and older participants, there was also transmission between age groups. Younger age (<27 vs. >40, AOR: 3.14; 95% CI: 1.54, 6.39), HIV (AOR: 1.97; 95% CI: 1.22, 3.18) and subtype 3a (AOR: 2.12; 95% CI: 1.33, 3.38) were independently associated with clustering.
  
  
  
  In this population of PWID from Vancouver, HCV among young injectors was seeded from many transmission events between HCV-infected older and younger injectors. Phylogenetic clustering was associated with younger age and HIV. These data suggest that HCV transmission among PWID is complex, with transmission occurring between and among older and younger PWID.
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia. Electronic address: bjacka@kirby.unsw.edu.au.
authors.forename: Brendan
authors.initials: B
authors.lastname: Jacka
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Applegate
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Art F
authors.initials: AF
authors.lastname: Poon
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Jayna
authors.initials: J
authors.lastname: Raghwani
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; School of Public Policy, Simon Fraser University, Vancouver, BC, Canada.
authors.forename: Kora
authors.initials: K
authors.lastname: DeBeck
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Department of Family Practice, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Milloy
authors.affiliation: BC Centre for Disease Control, Vancouver, BC, Canada.
authors.forename: Mel
authors.initials: M
authors.lastname: Krajden
authors.affiliation: BC Centre for Disease Control, Vancouver, BC, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Olmstead
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Joy
authors.affiliation: Department of Epidemiology, Brown University, Providence, RI, USA.
authors.forename: Brandon D L
authors.initials: BD
authors.lastname: Marshall
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Kanna
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Pybus
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Viviane Dias
authors.initials: VD
authors.lastname: Lima
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK; Virus Reference Department, Public Health England, London, UK.
authors.forename: Gkikas
authors.initials: G
authors.lastname: Magiorkinis
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Francois
authors.initials: F
authors.lastname: Lamoury
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Evan
authors.initials: E
authors.lastname: Wood
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000635:transmission*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D015819:Substance Abuse, Intravenous / Q000150:complications*
keywords: Age; HCV; HIV; Injection drug use; Molecular epidemiology; Phylogenetics; Transmission