Brendan Jacka1, Tanya Applegate2, Art F Poon3, Jayna Raghwani4, P Richard Harrigan3, Kora DeBeck5, M-J Milloy6, Mel Krajden7, Andrea Olmstead7, Jeffrey B Joy8, Brandon D L Marshall9, Kanna Hayashi8, Oliver G Pybus4, Viviane Dias Lima3, Gkikas Magiorkinis10, Julio Montaner3, Francois Lamoury2, Gregory J Dore2, Evan Wood3, Jason Grebely2. 1. Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia. Electronic address: bjacka@kirby.unsw.edu.au. 2. Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Australia, Sydney, NSW, Australia. 3. 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. 4. Department of Zoology, University of Oxford, Oxford, UK. 5. BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada; School of Public Policy, Simon Fraser University, Vancouver, BC, Canada. 6. 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. 7. BC Centre for Disease Control, Vancouver, BC, Canada. 8. BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada. 9. Department of Epidemiology, Brown University, Providence, RI, USA. 10. Department of Zoology, University of Oxford, Oxford, UK; Virus Reference Department, Public Health England, London, UK.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND & AIMS: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
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