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Hepatitis C reinfection following successful direct-acting antiviral therapy among patients attending a multidisciplinary treatment centre for people who use drugs in Zurich, Switzerland

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Abstract

Background and Aim: On-going risk-exposure followed by reinfection may jeopardize hepatitis C elimination efforts among people who use drugs. We estimated the HCV reinfection incidence in patients who successfully completed HCV therapy and attended a low-threshold access centre for comprehensive addiction medicine. Methods: Retrospective chart review was undertaken, in a convenience sample of patients with opioid/cocaine use disorders who achieved sustained viral response (SVR) after direct-acting antiviral (DAA) therapy in Zurich, Switzerland between April 2015 and July 2019 (n = 153). HCV reinfection incidence in patients with and without on-going drug use was calculated. Results: 79% of the patients were in opioid agonist treatment, and 19% were being managed for other medical or psychiatric conditions. 58% used drugs after SVR, of whom 49% injected. The follow-up period totalled 346 (median 2.1) person-years (py). Overall HCV reinfection incidence was 1.2 (CI-95: 0.3 to 3.0) per 100 py and 1.6 (0.2 to 5.8) in patients with drug use after SVR. Conclusion: The risk of HCV reinfection after DAA therapy in persons who use drugs can be low if, after SVR, patients remain in care in a well developed comprehensive harm reduction setting.

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Background We aim to describe the general characteristics of how the Canadian newspaper The Globe and Mail reports on opioid-related news, the opioid crisis and its victims, and explore how Canadians’ perceptions of the opioid crisis could have developed over time from this reporting. The Globe and Mail has the highest circulation among Canadian newspapers and is Canada’s newspaper of record. Methods Reviewers performed independent, blinded bibliometric searches of all The Globe and Mail articles archived in the Canadian Periodicals Index Quarterly spanning an 18-year period (1 January 2000–1 June 2018) related to the keywords “opioids” or “drugs and opioids” and “opiates”. Independently and in duplicate, reviewers manually extracted qualitative data from articles and identified emergent themes. Articles were screened independently by both reviewers based on the inclusion criteria. Conflicts were resolved by discussion and consensus. Social representation theory was used as a framework for describing how the opioid crisis is portrayed in Canada. Results Our search yielded 650 relevant opioid articles. The number of articles peaked in 2009, 2012, and in 2016, coinciding with major developments in the epidemic. The language used in this discourse has evolved over the years and has slowly shifted towards less stigmatizing language. Content analysis of the articles revealed common social representations attributing responsibility to pharmaceutical companies, physicians, and foreign countries. Conclusions The Globe and Mail’s coverage of the opioid crisis is focused on basic social representations and attributed responsibility for the crisis to a few collectives. A shift toward coverage of the root causes of the opioid epidemic could positively influence the general public’s perception of the opioid crisis and promote deeper understanding of the issue. Journalists face several obstacles to achieve greater focus and framing of the opioid crisis; a closer working relationship between the media and the research community is needed.
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Background: /Aims: HCV reinfection following successful treatment can compromise treatment outcome. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT). Methods: Bibliographic databases and conference abstracts were searched for studies assessing post-treatment HCV reinfection rate among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression to explore heterogeneity. Results: Thirty-six studies were included (person-years follow-up=6,311). The overall rate of HCV reinfection was 5.9/100 person-years (95%CI: 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95%CI: 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95%CI: 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95%CI: 3.1-9.5), and direct-acting antiviral therapy (3.9/100 person-years; 95%CI: 2.5-5.9). In stratified analysis, reinfection rate was 1.4/100 person-years (95%CI: 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95%CI: 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95%CI: 3.4-12.7) among people with recent drug use, not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate [adjusted Rate Ratio (aRR) per year increase in mean/median follow-up: 0.77, 95%CI: 0.69-0.86]. Compared with people receiving OAT with no recent drug use, those with recent drug use, receiving OAT (aRR: 3.50, 95%CI: 1.62-7.53), and those with recent drug use, not receiving OAT (aRR: 3.96, 95%CI: 1.82-8.59) had higher reinfection rates. Conclusion: HCV reinfection risk following treatment increased among people with recent drug use compared to those receiving OAT. Lower rates in studies with longer follow-up suggested higher reinfection risk early post-treatment.
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In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating HCV infection decreased substantially after the introduction of direct-acting antivirals (DAAs). Among men who have sex with men, the increase in DAAs uptake and efficacy was counterbalanced by frequent incident HCV infections.
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Introduction: Globally, there is a considerable burden of HCV and HIV infections among people who inject drugs (PWID) and transmission of both infections continues. Needle and syringe programme (NSP) and opioid substitution therapy (OST) coverage remains low, despite evidence demonstrating their prevention benefit. Direct-acting antiviral therapies (DAA) with HCV cure >95% among PWID provide an opportunity to reverse rising trends in HCV-related morbidity and mortality and reduce incidence. However, HCV testing, linkage to care, and treatment remain low due to health system, provider, societal, and patient barriers. Between 2015 and 2030, WHO targets include reducing new HCV infections by 80% and HCV deaths by 65%, and increasing HCV diagnoses from <5% to 90% and number of eligible persons receiving HCV treatment from <1% to 80%. This commentary discusses why PWID should be considered as a priority population in these efforts, reasons why this goal could be attainable among PWID, challenges that need to be overcome, and key recommendations for action. Discussion: Challenges to HCV elimination as a global health concern among PWID include poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low HCV testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. Key recommendations for action include reforming drug policies (decriminalization of drug use and/or possession, or providing alternatives to imprisonment for PWID; decriminalization of the use and provision of sterile needles-syringes; and legalization of OST for people who are opioid dependent), scaling up and improving funding for harm reduction services, making health services accessible for PWID, supporting community empowerment and community-based programmes, improving access to affordable diagnostics and medicines, and eliminating stigma, discrimination, and violence against PWID. Conclusions: The ambitious targets for HCV elimination set by WHO are achievable in many countries, but will require researchers, healthcare providers, policy makers, affected communities, advocates, the pharmaceutical and diagnostics industries, and governments around the world to work together to make this happen.
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Purpose of review: The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk - such as people who inject drugs (PWID) - irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID. Recent findings: There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential 'prevention benefit' of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and 'prevention benefit' hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures. Summary: Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.
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Background: The aim of this analysis was to calculate the incidence of HCV reinfection and associated factors among two clinical trials of HCV DAA treatment in people with recent injecting drug use or currently receiving OAT. Methods: Participants who achieved an end-of-treatment response in two clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in eight countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. Results: Seventy-three percent of the population at risk for reinfection (n=177; median age 48 years, 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median 1.8 years, range 0.2-2.8). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% CI 1.6-6.3) overall and 17.9/100 person-years (95% CI 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. Conclusions: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination.
Article
Background: Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) has been shown to be effective among PWID, but more real-world data on treatment outcomes is needed. The aim of this analysis was to assess the efficacy of DAA therapy, and the rate of reinfection and mortality among people attending an inner-city community health centre in Victoria, Canada. Methods: In this retrospective study, patients treated with DAA therapy between November 2014 and Dec 31, 2017 were included. Retrospective chart review was performed to assess recent injecting drug use (IDU, previous six months) or receipt of opioid agonist treatment (OAT). The primary endpoint was Sustained Virologic Response (SVR12). Secondary endpoints included HCV reinfection and mortality. Results: Of 270 patients who initiated DAA treatment (31% female), 20% (n=54) had HIV/HCV coinfection, 32% (n=84) had cirrhosis, 67% (n=181) had genotype 1, 6% (n=15) had genotype 2, 26% (n=69) had genotype 3. 46% (n=125) of patients were receiving OAT and 49% (n=132) reported recent IDU. 98% (n=265) completed treatment; two people stopped due to mental health, two people died, and one was non-adherent. 92% (249 of 270) achieved SVR12. 16 patients with End of Treatment (EOT) response did not have a SVR12; 7 were lost to follow-up; 2 people refused bloodwork; 2 people died; 1 had reinfection; and 4 had viral relapse. There was no difference in SVR12 by OAT (OAT, 93% vs. no OAT, 91%, P=0.435), recent injecting drug use (yes, 92% vs. no, 92%, P=0.904), or HIV status (HIV, 92% vs. no HIV, 94%, P=0.498). Eight cases of HCV reinfection were observed over 253 person-years of follow up (3.2 cases per 100 person-years; 95% CI 1.6-6.3). Twenty people died (6.3 per 100 person-years; 95% CI 3.9-10.3), including two during therapy (drug overdose, n=2) and 18 following therapy completion (drug overdose, n=7). Conclusion: This study demonstrates that DAA treatment is effective among a marginalized population receiving care in an inner-city community health centre. The high mortality in this study highlights the importance of integrating HCV care within a framework addressing drug-related harms, preventing overdose mortality, addressing social inequalities, and improving the health of PWID.
Article
Background: Treating chronic hepatitis C virus (HCV) infection among PWID (people who inject drugs) is crucial to achieve the WHO goal of HCV elimination, as this population is highly affected and carries a high risk of transmission. The aim of our study was to provide real-life data on HCV treatment among PWID either in opioid agonist treatment (OAT) or in heroin-assisted treatment (HAT) in a low-threshold access primary care-based addiction medicine institution. Methods: We conducted a retrospective chart analysis of patients treated with direct-acting antivirals (DAA) between 10/2014 and 08/2017 in the Arud outpatient clinics in Zurich, Switzerland. We reported patient and treatment characteristics and substance use. The outcomes were sustained virological response (SVR) by intention-to-treat (ITT) and modified ITT (mITT) analyses, excluding patients with missing SVR data. Results: We included 64 patients in our analysis. Forty-two (66%) were in OAT, and 22 (34%) were in HAT. Twenty-six patients (41%) reported harmful alcohol use, and 9 patients (14%) reported injecting drug use during DAA treatment. Every patient completed the treatment. Fifty-nine out of 64 achieved SVR resulting in an ITT SVR rate of 92.2%. Two patients had virological failure. Three patients were lost to follow-up between the end of treatment and SVR12 visit. Excluding these 3 patients, our study showed an mITT SVR rate of 96.7%. Conclusion: PWID can be treated with DAA treatment integrated in OAT and HAT with an excellent SVR rate. OAT and HAT programs should offer integrated HCV treatment to their patients.
Article
Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2–6/100 person years among PWID to 10–15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections.
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The use of confidence intervals has become standard in the presentation of statistical results in medical journals. Calculation of confidence limits can be straightforward using the normal approximation with an estimate of the standard error, and in particular cases exact solutions can be obtained from published tables. However, for a number of commonly used measures in epidemiology and clinical research, formulae either are not available or are so complex that calculation is tedious. The author describes how an approach to confidence interval estimation which has been used in certain specific instances can be generalized to obtain a simple and easily understood method that has wide applicability. The technique is applicable as long as the measure for which a confidence interval is required can be expressed as a monotonic function of a single parameter for which the confidence limits are available. These known confidence limits are substituted into the expression for the measure--giving the required interval. This approach makes fewer distributional assumptions than the use of the normal approximation and can be more accurate. The author illustrates his technique by calculating confidence intervals for Levin's attributable risk, some measures in population genetics, and the "number needed to be treated" in a clinical trial. Hitherto the calculation of confidence intervals for these measures was quite problematic. The substitution method can provide a practical alternative to the use of complex formulae when performing interval estimation, and even in simpler situations it has major advantages.
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A 'risk environment' framework promotes an understanding of harm, and harm reduction, as a matter of 'contingent causation'. Harm is contingent upon social context, comprising interactions between individuals and environments. There is a momentum of interest in understanding how the relations between individuals and environments impact on the production and reduction of drug harms, and this is reflected by broader debates in the social epidemiology, political economy, and sociology of health. This essay maps some of these developments, and a number of challenges. These include: social epidemiological approaches seeking to capture the socially constructed and dynamic nature of individual-environment interactions; political-economic approaches giving sufficient attention to how risk is situated differentially in local contexts, and to the role of agency and experience; understanding how public health as well as harm reduction discourses act as sites of 'governmentality' in risk subjectivity; and focusing on the logics of everyday habits and practices as a means to understanding how structural risk environments are incorporated into experience. Overall, the challenge is to generate empirical and theoretical work which encompasses both 'determined' and 'productive' relations of risk across social structures and everyday practices. A risk environment approach brings together multiple resources and methods in social science, and helps frame a 'social science for harm reduction'.
Mortalität in substitutionsgestützten Behandlungen im Kanton Zürich, 1992-2016
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Nordt, C., & Herdener, M. (2018). Mortalität in substitutionsgestützten Behandlungen im Kanton Zürich, 1992-2016. In Forschungsgruppe Substanzstörungen der Psychiatrischen Universitätsklinik Zürich (Ed.), Resultate aus der Begleitevaluation der Methadonbehandlungen im Kanton Zürich. Zürich: Psychiatrische Universitätsklinik.
Reinfection following successful direct-acting antiviral therapy for hepatitis C infection among people who inject drugs
  • Cunningham