Nazrul Islam1, Mel Krajden2, Jean Shoveller3, Paul Gustafson4, Mark Gilbert5, Jane A Buxton1, Jason Wong1, Mark W Tyndall1, Naveed Zafar Janjua6. 1. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control, Vancouver, BC, Canada. 2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control, Vancouver, BC, Canada. 3. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada. 4. Department of Statistics, University of British Columbia, Vancouver, BC, Canada. 5. British Columbia Centre for Disease Control, Vancouver, BC, Canada; Ontario HIV Treatment Network, Toronto, ON, Canada. 6. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control, Vancouver, BC, Canada. Electronic address: naveed.janjua@bccdc.ca.
Abstract
BACKGROUND: People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. METHODS: We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). FINDINGS: 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). INTERPRETATION: The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. FUNDING: The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.
BACKGROUND:People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. METHODS: We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). FINDINGS: 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). INTERPRETATION: The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. FUNDING: The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.
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