Molecular Epidemiology of Full-Length Hepatitis C Virus Genomes among Injecting Drug Users with Recent Infection: The Inc3 Study


Author: Rodrigo C, Eltahla A, Bull RA, Luciani F, Grebely J, Dore GJ, Applegate T, Page K, Bruneau J, Morris MD, Cox AL, Osburn W, Kim AY, Shoukry NH, Lauer GM, Maher L, Hellard M, Schinkel J , Prins M and Lloyd AR on behalf of the InC3 Study Group

Theme: Epidemiology & Public Health Research Year: 2016

MOLECULAR EPIDEMIOLOGY OF FULL-LENGTH, EARLY INFECTION, HEPATITIS C VIRUS
GENOMES AMONG INJECTING DRUG USERS WITH RECENT INFECTION: THE InC3 STUDY
Rodrigo C
1
, Eltahla A
1
, Bull RA1
, Luciani F
1
, Grebely J
2
, Dore GJ2
, Applegate T
2
, Page K
3
,
Bruneau J
4
, Morris MD5
, Cox AL6
, Osburn W6
, Kim AY7
, Shoukry NH4
, Lauer GM7
, Maher L
2
,
Hellard M
9,10,11, Schinkel J
8,12 , Prins M
8,12 and Lloyd AR1
on behalf of the InC3 Study Group
1School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia, 2
The
Kirby Institute, UNSW Australia , Sydney, NSW, Australia, 3Department of Internal Medicine,
University of New Mexico, Albuquerque, NM, USA, 4CRCHUM, Université de Montréal, Montreal,
QC, Canada, 5Department of Epidemiology and Biostatistics, University of California, San
Francisco, San Francisco, CA, USA, 6Department of Medicine, Johns Hopkins Medical Institutions,
Baltimore, MD, USA, 7Harvard Medical School, Boston, MA, USA, 8Department of Internal
Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and
Immunity Amsterdam, Academic Medical Center, Meibergdreef, Amsterdam, The Netherlands,
9Burnet Institute, Melbourne, VIC, Australia, 10Alfred Hospital, Department of Infectious Diseases,
Melbourne, Australia, 11Department of Epidemiology and Preventive Medicine, Monash University,
Australia, 12GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands
Background: The molecular epidemiology of hepatitis C virus (HCV) infection has typically been
studied in individual countries worldwide, however little is known about cross-continental patterns
and about the characteristics of the viruses associated with incident infection.
Methods: The International collaborative of Incident HIV and Hepatitis C in Injecting Cohorts
(InC3) is a collaboration of nine well characterized prospective cohorts on injecting drug users.
The sample repository of InC3 collaboration was searched to find all samples within 180 days of
infection.An optimized laboratory pipeline was used to generate full-length HCV sequences by
next generation sequencing. The output of was analysed with a bioinformatics pipeline to generate
consensus sequences and these were used in phylogenetic analysis to understand the crosscontinental molecular epidemiology of early HCV infection and the demographic / behavioural
associations with clustering.
Results: The cohorts were from three continents: North America (n=4), Australia (n=4) and
Europe (n=1). One hundred and ninety full-length HCV genomes were amplified. Genomes from
the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in maximum likelihood
phylogenetic analysis to identify clusters of molecularly related sequences. Using full genome
trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs (mean patristic
distance cut-off; 0.01%, 95% bootstrap support). Of these, 13 each had exclusively Australian and
North American sequences. Older age, non-Caucasian ethnicity, Australian origin, and current
imprisonment were significantly associated with clustering in bivariate analysis, and the first two
associations remained statistically significant after binary logistic regression analysis.
Conclusions: We have established the largest, international, acute HCV genomic data repository
available to-date worldwide. In the phylogenetic analysis of these sequences clustering was
evident almost exclusively within-continents. This suggests that HCV evolves in micro-epidemics
within geographically isolated communities and this can have implicatons for a universal vaccine.
Disclosure statement: The authors have no conflicts of interest to declare

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