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Background: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender., Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884., Findings: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I 2 =98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I 2 =97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I 2 =66·9%) and HCV (1·5, 1·3-1·8; I 2 =70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I 2 =55·3%) and HCV (1·2, 1·1-1·3; I 2 =43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk., Interpretation: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs., Funding: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO., Competing Interests: Declaration of interests AA acknowledges support through postdoctoral fellowships from the Canadian Institute of Health Research (CIHR), Fonds de recherche du Québec – Santé (FRQ-S), and the Canadian Network on Hepatitis C. MA reports grants paid to his institution from the Public Health Agency of Canada and grants from the Ministère de la santé et des services sociaux du Québec, during the conduct of this study, and grants from the CIHR, outside the submitted work. JA reports grants from the National Institutes of Health (NIH), during the conduct of this study. JB reports consulting fees from Gilead Sciences, AbbVie, and Cepheid; payment or honoraria from Gilead Sciences for an educational event; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Gilead Sciences, as part of an NIH R01 grant, outside of the submitted work. CSC reports grants from Gilead Sciences, Janssen Pharmaceuticals, and GSK (paid to the University of Calgary); consulting fees from Roche Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals (paid to the University of Calgary, on behalf of the Canadian Hepatitis B Virus [HBV] Network), and Altimmune (paid to the University of Calgary, on behalf of the Canadian HBV Network); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events through Gilead Sciences; and patents planned, issued, or pending (PCT/CA2021/050234; international patent application title: polypeptides directed against viral infection and uses thereof; compositions and methodologies for the detection and treatment of HBV infection; USA; 62/982,474; Feb 28, 2020). SC reports payments for chairing or presenting at a European HIV Testing Week webinar from the Centre of Excellence for Health, Immunity and Infections, outside the submitted work. KH reports financial support for the present manuscript paid to her institution from the US National Institute of Drug Abuse (NIDA; Vancouver Drug Users Study: the impacts of evolving drug use patterns on HIV/AIDS; U01DA038886), the Michael Smith Foundation for Health Research Scholar Award, and St Paul's Foundation, and grants or contracts from the CIHR and the William and Ada Isabelle Steel Fund through Simon Fraser University (paid to institution) and the British Columbia Centre on Substance Use (paid to KH). GM reports grants or contracts from AbbVie (clinic support, advisory board, and speaker fees), the Canadian Network on Hepatitis C (research support), Coverdale (clinic support), Gilead Sciences (clinic support and speakers fees), International Network on Health and Hepatitis in Substance Users (INHSU; speaker fees), and TD Bank (clinic support); payment or honoraria from the Canadian Association for the Study of the Liver (scientific planning committee for web-based learning, conjoint with AbbVie; payment to institution), AbbVie (speakers fees for educational podcasts and brochure; payment partly to institution and partly to GM), Gilead Sciences (speaker fees; payment partly to institution and partly to GM), and ECHO plus (honorarium for speaking); and support for attending meetings or travel, or both, from INHSU and being on the advisory board for AbbVie and Gilead. JGW reports grants and contracts from Gilead Sciences and FIND, The Global Alliance for Diagnostics. MH reports having a leadership or fiduciary role as trustee of the Society for the Study of Addiction. All other authors declare no competing interests. Declaration of interests for the members of the HIV and HCV Incidence Review Collaborative Group are provided in the appendix (p 52)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In 2020, the Australian state of Victoria experienced the longest COVID-19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de-identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time-series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Monitoring trends in hepatitis C virus (HCV) incidence is critical for evaluating strategies aimed at eliminating HCV as a public health threat. We estimate HCV incidence and assess trends in incidence over time among primary care patients., Methods: Data were routinely extracted, linked electronic medical records from 12 primary care health services. Patients included were aged ≥16 years, tested HCV antibody negative on their first test recorded and had at least one subsequent HCV antibody or RNA test (January 2009-December 2020). HCV incident infections were defined as a positive HCV antibody or RNA test. A generalised linear model assessed the association between HCV incidence and calendar year., Results: In total, 6711 patients contributed 17,098 HCV test records, 210 incident HCV infections and 19,566 person-years; incidence was 1.1 per 100 person-years (95% confidence interval (CI): 0.9 to 1.2). Among 559 (8.2%) patients ever prescribed opioid-related pharmacotherapy (ORP) during the observation period, 135 infections occurred during 2,082 person-years (incidence rate of 6.5 per 100 person-years (95% CI: 5.4 to 7.7)). HCV incidence declined 2009-2020 overall (incidence rate ratio per calendar year 0.8 (95% CI: 0.8 to 0.9) and among patients ever prescribed ORT (incidence rate ratio per calendar year 0.9, 95% CI: 0.75 to 1.0)., Conclusion: HCV incidence declined among patients at primary care health services including among patients ever prescribed ORP and during the period following increased access to DAA therapy., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in  people who inject drugs (PWID)., Methods: A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models., Results: The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76)., Conclusions: Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: With the development of new highly efficacious direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV), the concept of treatment as prevention is gaining credence. To date, the majority of mathematical models assume perfect mixing, with injectors having equal contact with all other injectors. This article explores how using a networks-based approach to treat people who inject drugs (PWID) with DAAs affects HCV prevalence. Using observational data, we parameterized an exponential random graph model containing 524 nodes. We simulated transmission of HCV through this network using a discrete time, stochastic transmission model. The effect of five treatment strategies on the prevalence of HCV was investigated; two of these strategies were (1) treat randomly selected nodes and (2) "treat your friends," where an individual is chosen at random for treatment and all their infected neighbors are treated. As treatment coverage increases, HCV prevalence at 10 years reduces for both the high- and low-efficacy treatment. Within each set of parameters, the treat your friends strategy performed better than the random strategy being most marked for higher-efficacy treatment. For example, over 10 years of treating 25 per 1,000 PWID, the prevalence drops from 50% to 40% for the random strategy and to 33% for the treat your friends strategy (6.5% difference; 95% confidence interval: 5.1-8.1)., Conclusion: Treat your friends is a feasible means of utilizing network strategies to improve treatment efficiency. In an era of highly efficacious and highly tolerable treatment, such an approach will benefit not just the individual, but also the community more broadly by reducing the prevalence of HCV among PWID., (© 2014 by the American Association for the Study of Liver Diseases.)

Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.

Objectives: To develop a mathematical model to project the potential impact of hepatitis C virus (HCV) treatment on HCV infection prevalence among people who inject drugs (PWID)., Design and Setting: An existing model of HCV transmission among PWID was parameterised using data from Victoria, Australia, including specific parameter estimates of the number of people who are currently active injecting drug users, average duration of injecting, chronic HCV infection prevalence among PWID, annual mortality, and annual HCV treatment rate. We also explored the impact of prevalence uncertainty, program scale-up, and new treatments., Main Outcome Measure: Prevalence of chronic HCV infection among people who are currently active injecting drug users., Results: With annual treatment rates of 13, 17, or 25 per 1000 PWID, the model predicts relative prevalence reductions of 20%, 30%, and 50%, respectively, within 30 years. If new treatments giving higher sustained viral response rates are available in 5 years, estimated impact is increased by 21%–23% at 15 years, and 17%–38% at 30 years, depending on treatment rates., Conclusions: This model suggests that modest rates of current HCV treatment among PWID in Victoria, Australia could halve HCV infection prevalence among PWID in 30 years. This finding suggests that interventions aimed at increasing access to HCV treatment in community clinics will benefit individual PWID and reduce HCV infection prevalence.