Full length articleEvidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection☆
Introduction
It is well established that people who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection. Globally, there are an estimated 16 million PWID who are currently injecting (Mathers et al., 2008) and of these, 10 million are estimated to have been infected with HCV (Nelson et al., 2011). Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cleared with antiviral treatment and establishment of sustained viral response (SVR). Currently, there is low initiation of HCV antiviral treatment among PWID, which likely relates to concerns of adherence to and reinfection post-treatment (Martin et al., 2013, Iversen and Maher, 2012). Regardless, recent studies have indicated treatment outcomes to be acceptable and risk of HCV reinfection to be relatively low among PWID, albeit based on only a few small-scale studies conducted among selected populations in clinical and harm reduction settings often with limited follow-up (Aspinall et al., 2013, Arain and Robaeys, 2014, Grady et al., 2013). Modelling work has further demonstrated that treating PWID is cost-effective and has the potential to reduce HCV transmission and prevalence in this population (Martin et al., 2011a, Martin et al., 2013). Therefore, recommendations state that treatment is not to be withheld from an individual based on injection status alone (EASL, 2015).
After being deemed one of the greatest public health challenges of our time, HCV was made a priority by the Scottish Government and a comprehensive Action Plan was formulated to curb the predominately injecting-related epidemic (Chisholm, 2004, Scottish Government Health Department, 2008). As a result, the overall number of people initiated on antiviral therapy in Scotland more than doubled between 2007 and 2010 with ∼1000 now treated per year and the vast majority (>80%) of these report having ever injected drugs (Health Protection Agency (HPA), 2013).
Given this recent and anticipated future upscale in treatment provision among PWID a better understanding is needed of the injecting risk behaviours and potential for reinfection post-SVR. Our principal objective, therefore, was to establish evidence and predictors of continued engagement in injection drug use post-SVR using a record-linkage approach involving both HCV treatment and injecting-related hospitalisation data for a large nationally representative cohort of over 1000 PWID.
Section snippets
Study population, data sources, and linkage procedure
This paper utilised a retrospective cohort of Scottish PWID derived from the HCV Clinical Database using data linked from four additional national databases. Health Protection Scotland (HPS) holds and maintains individual patient data for all HCV diagnosed persons who attended a specialist centre for HCV treatment and management across Scotland, referred to as the HCV Clinical Database. This database includes information on patient demographics, virology, treatment episodes, epidemiological
Sample characteristics (Table 1)
Table 1 displays the demographic and behavioural characteristics of the cohort with regard to our primary outcome (i.e., an injection-related hospital episode or death post-SVR). The average age at SVR was 39.6 years (standard deviation ± 8.2 years; range 19.0–67.7 years), and the majority were male (76%). The majority of the cohort (76%) attained SVR between 2006 and June 2012. A history of an IRH pre-SVR was found for 427 (37%) of the cohort, of which 222 had an IRH within three years prior to
Discussion
With highly effective but costly HCV treatments on the horizon and potential demand for treatment to increase particularly among the population who injects drugs, it is essential that the behaviours which pose a risk of reinfection post-SVR are well understood. There have been few small-scale studies examining engagement in injection drug use post-HCV antiviral treatment induced SVR. These studies rely on participation, accurate self-report by PWID, and have varied in respect of recruitment
Role of funding source
This project was supported by funding from the Scottish Government.
Contributors
HV performed the data analysis and interpretation under the supervision of JL, and drafted the paper under the supervision of SH and DG. SH and DG conceived, proposed, and oversaw the scope of the project. AW deterministically linked hospitalisation and mortality data with HCV Clinical and Diagnosis databases. All other authors provided clinical data, manuscript revisions, and approved final submission.
Conflict of interest statement
None declared.
Acknowledgements
Clinical Database Monitoring Committee, Clinical Database Managers, Data Entry Clerks, and HCV Clinical Leads who routinely monitor data which are entered onto the database. Health Protection Scotland, Information Services Division, Scotland, who hold all Scottish morbidity (hospitalisation) and mortality data, and who performed the initial linkage between the databases.
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Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs
2022, Journal of HepatologyCitation Excerpt :The test database was then used to follow up the cohort for HCV reinfection by searching for subsequent HCV RNA/Ag tests (which we refer to as follow-up tests performed post-SVR); those with both a confirmatory negative SVR test and at least 1 follow up RNA/Ag test (positive or negative) were used to estimate reinfection rates (Fig. 1). Information on opioid or injection-related hospital admissions (identified using ICD-10 codes described previously26 and used as an indicator of recent or ongoing injection risk), death and migration were ascertained through linkage to Scottish Morbidity Record data, National Records of Scotland mortality data and the Community Health Index database, respectively. Diagnosed HCV reinfection was defined as a positive HCV RNA/Ag test during follow-up.
Belgian experience with direct acting antivirals in people who inject drugs
2017, Drug and Alcohol DependenceCitation Excerpt :Based on the patient files, only 2.5% (1/40) of the ex-PWID who were treated in the past with interferon were re-infected. This is comparable to earlier studies who also have shown low reinfection rates (Aspinall et al., 2013; Dalgard et al., 2002; Grady et al., 2013; Midgard et al., 2016; Valerio et al., 2015). However, due to the shift to the target of viral elimination, the potential risk of reinfection should not influence the physicians’ judgement, as these patients are the key targets to treat in order to achieve viral elimination.
Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs
2016, Drug and Alcohol DependenceCitation Excerpt :Drawing on data on the average incidence of HCV infection among active PWID in the Scottish community, estimated to be 10.0/100 PY across the 2008/09, 2010 and 2011/12 sweeps of the Needle Exchange Surveillance Initiative (University of the West of Scotland et al., 2008), would suggest that individuals in this study, who have undergone treatment and successfully cleared their infection, had, in comparison, fewer injecting risk behaviours post SVR; it’s plausible that many in the cohort had indeed ceased injecting prior to commencement of treatment. However there remains at least a minority of individuals who continue to behave in a way that puts them at risk of becoming reinfected, also observed by Valerio et al. (2015), and these individuals must be identified and closely monitored via periodic RNA testing as suggested in the EASL guidelines (EASL, 2014). Our data suggest that the frequency of RNA testing, post-SVR, among successfully treated PWID has decreased over time; PWID treated recently, i.e., 2006–2009, were 50% less likely to receive an RNA test when compared with those treated during 2000–2002.
Management of the patient with SVR
2016, Journal of HepatologyCitation Excerpt :The rates of reinfection are higher among those who returned to drug use vs. those with a history of injection drug [44]. In a longitudinal study of 1170 PWIDs followed for 3 years after SVR, 11% were hospitalized or died from injection-related complications with those with pre-SVR history of hospitalization for alcohol or injection drug related events at highest risk [46]. These studies highlight the importance of drug treatment programs including opiate substitution and needle exchange programs as an important component of reducing harm including the risk of reinfection.
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2018, Liver InternationalStrategies to control HIV and HCV in methadone maintenance treatment in Guangdong Province, China: A system dynamic modeling study
2018, Substance Abuse: Treatment, Prevention, and Policy
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Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org and by entering doi:10.1016/j.drugalcdep.2015.06.032.