title: Assessing the feasibility of hepatitis C virus vaccine trials: results from the Hepatitis C Incidence and Transmission Study-community (HITS-c) vaccine preparedness study.
abstract: Efficacy trials of preventive hepatitis C virus (HCV) vaccine candidates raise challenging scientific and ethical issues. Based on data from the first 3 years of a community-based prospective observational study - the Hepatitis C Incidence and Transmission Study-community (HITS-c) - this paper examines the feasibility of conducting trials of candidate HCV vaccines with people who inject drugs (PWID) in Sydney, Australia. Of the 166 PWID confirmed HCV antibody negative and eligible for enrolment, 156 (94%) completed baseline procedures. Retention was high, with 89% of participants retained at 48 weeks and 76% of participants completing at least 75% of study visits within 2 weeks of schedule. The rate of primary HCV infection was 7.9/100 py (95% CI 4.9, 12.7). Of the 17 incident cases, 16 completed at least one follow-up assessment and 12 (75%) had evidence of chronic viraemia with progression to chronic HCV infection estimated to be 6/100 py. Power calculations suggest a chronic HCV infection rate of at least 12/100 py (primary HCV infection rate 16/100 py) will be required for stand-alone trials of highly efficacious candidates designed to prevent chronic infection. However, elevated primary HCV infection was observed among participants not receiving opioid substitution therapy who reported heroin as the main drug injected (26.9/100 py, 95% CI 14.5, 50.0) and those who reported unstable housing (23.5/100 py, 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100 py, 95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100 py, 95% CI 9.8, 56.7) in the 6 months prior to baseline. These data suggest that it is possible to recruit and retain at-risk PWID who adhere to study protocols and that modification of eligibility criteria may identify populations with sufficiently high HCV incidence. Results support the feasibility of large multi-centre HCV vaccine trials, including in the Australian setting.
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Bethany
authors.initials: B
authors.lastname: White
authors.affiliation: Australian Injecting & Illicit Drug Users League (AIVL), Sydney Building, Level 2/112-116 Alinga Street, Canberra ACT 2600, Australia.
authors.forename: Annie
authors.initials: A
authors.lastname: Madden
authors.affiliation: Academic Medical Centre, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, The Netherlands; Cluster of Infectious Diseases, Department of Research, Public Health Service, Amsterdam, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.affiliation: Centre for Population Health, The Macfarlane Burnet Institute for Medical Research, 85 Commercial Road, Melbourne, Victoria 3004, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Handan
authors.initials: H
authors.lastname: Wand
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, 50 Beale Street, Suite 1200, San Francisco, CA 94105, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: lmaher@kirby.unsw.edu.au.
authors.forename: Lisa
authors.initials: L
authors.lastname: Maher
mesh_terms: D000328:Adult; D001315:Australia / Q000453:epidemiology; D005240:Feasibility Studies; D005260:Female; D006526:Hepatitis C / Q000453:epidemiology / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D015994:Incidence; D008297:Male; D010349:Patient Compliance / Q000706:statistics & numerical data; D010352:Patient Dropouts / Q000706:statistics & numerical data; D018579:Patient Selection; D012107:Research Design; D012309:Risk-Taking; D018401:Sample Size; D015819:Substance Abuse, Intravenous; D016896:Treatment Outcome; D014761:Viral Hepatitis Vaccines / Q000627:therapeutic use*
chemical_list: D018937:Hepatitis C Antibodies; D014761:Viral Hepatitis Vaccines
keywords: Hepatitis C virus; People who inject drugs; Vaccine preparedness study