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Background: Limited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined., Methods: Unrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression., Results: Treatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35-56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32-5.41) after first treatment attempt., Conclusion: By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SO, MG, RHF, and VR report consultancy and speaker's fees from Gilead Sciences. MHel's institute receives funding from Gilead Sciences and AbbVie for investigator-initiated research on which MHel is a chief investigator. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Reversing declining rates of people initiating and completing hepatitis C (HCV) treatment, observed in many countries, is needed to achieve global HCV elimination goals. Providing financial incentives to increase HCV testing and treatment uptake among people at-risk of or living with HCV infection could be an effective intervention. We conducted a systematic review to assess evidence regarding the effectiveness of financial incentives to improve engagement and progression through the HCV care cascade., Methods: We searched MEDLINE, PubMed and EMBASE for studies published from January 2013 to January 2023 that evaluated financial incentives offered to people living with and at-risk of HCV to increase HCV antibody and or RNA testing, linkage to care, treatment initiation, treatment adherence, treatment completion, and sustained viral load (SVR) testing. Open-label randomised controlled trials (RCTs), controlled non-randomised studies, cohort or observation studies and mixed-methods studies were included, whereas literature reviews, case series and studies which did not report data were excluded., Results: We identified 1,278 studies, with 21 included after full-text screening (14,913 participants); three randomised controlled trials and 18 non-randomised studies. Studies evaluated incentives aimed at improving test uptake (n = 11), engagement in care (n = 13), treatment initiation (n = 8), adherence (n = 3), completion (n = 3) and attainment of SVR (n = 5). Findings provided inconclusive evidence for the effectiveness of incentives in improving engagement in the HCV cascade of care. Determining incentive effectiveness to improve care cascade engagement was limited by low quality study designs, heterogeneity in type (cash or voucher), value (US$5 to $600) and cascade stage being incentivised. No randomised controlled trials assessed the effectiveness of incentives to promote HCV testing, and none showed an impact on treatment uptake. In non-randomised studies (observational comparative), some evidence suggested that incentives promoted HCV testing, but evidence of their role in promoting linkage to care, HCV treatment adherence and treatment completion were mixed., Conclusion: Currently, there lacks high-quality evidence evaluating whether financial incentives improve HCV testing and treatment outcomes. Future research should seek to standardise methodologies, compare incentive types and values to enhance engagement in HCV care, and determine factors that support incentives effectiveness., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MWT has received investigator-initiated research funding, speakers honoraria and consultant fees from Gilead Sciences for activities unrelated to this work. AP has received investigator-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work. JSD and MEH receives funding from Gilead Sciences and Abbvie for investigator-initiated research, unrelated to the submitted work. MS has received investigator-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work. Burnet Institute receives funding support (outside this study) from the Victorian Government Operational Infrastructure Fund., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57 % in 2015 to 32 % in 2022. We aimed to investigate potential explanations for this decline., Methods: Changes in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours., Results: Overall prevalence of DBS HCV Ab declined rapidly and significantly from 57 % in 2015 to 32 % in 2022 (p < 0.001) however modified HCV Ab prevalence remained stable over time (85 % and 88 % in 2015 and 2022, respectively, p = 0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20 % in 1995 to 40 % in 2022 (p < 0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3 % in 1999 to 67 % in 2022 (p < 0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p < 0.001) however the short-term trend was not significant for recent receptive syringe sharing., Conclusion: The temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting., Competing Interests: Declaration of competing interest None of the authors have any competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57% in 2015 to 32% in 2022. We aimed to investigate potential explanations for this decline., Methods: Changes in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours., Results: Overall prevalence of DBS HCV Ab declined rapidly and significantly from 57% in 2015 to 32% in 2022 (p<0.001) however modified HCV Ab prevalence remained stable over time (85% and 88% in 2015 and 2022, respectively, p=0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20% in 1995 to 40% in 2022 (p<0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3% in 1999 to 67% in 2022 (p<0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p<0.001) however the short-term trend was not significant for recent receptive syringe sharing., Conclusion: The temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting., Competing Interests: Declaration of competing interest None of the authors have any competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C., Methods: Prospective single-arm study with recruitment between 9 November 2020 and 28 January 2021 and follow-up to 31 July 2021. Clients attending the supervised injecting facility were offered HCV RNA testing using the Xpert® HCV Viral Load Fingerstick (Cepheid, Sunnyvale, CA) PoCT. Participants with a positive HCV RNA test were prescribed direct acting antiviral (DAA) therapy. The primary endpoint was the proportion of clients who engaged in HCV RNA PoCT, compared to a historical comparator group when venepuncture-based hepatitis C testing was standard of care., Results: Among 1618 clients who attended the supervised injecting facility during the study period, 228 (14%) engaged in PoCT. This was significantly higher than that observed in the historical comparator group (61/1,775, 3%; p < 0.001). Sixty-five (28%) participants were HCV RNA positive, with 40/65 (62%) receiving their result on the same day as testing. Sixty-one (94%) HCV RNA positive participants were commenced on DAA therapy; 14/61 (23%) started treatment on the same day as diagnosis. There was no difference in the proportion of HCV RNA positive participants commenced on treatment with DAA therapy when compared to the historical comparator group (61/65, 94% vs 22/26, 85%; p = 0.153). However, the median time to treatment initiation was significantly shorter in the PoCT cohort (2 days (IQR 1-20) vs 41 days (IQR 22-76), p < 0.001). Among participants who commenced treatment and had complete follow-up data available, 27/36 (75%) achieved hepatitis C cure., Conclusions: HCV RNA PoCT led to a significantly higher proportion of clients attending a supervised injecting facility engaging in hepatitis C testing, whilst also reducing the time to treatment initiation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MM has received honoraria for speaking duties for Gilead Sciences. MS has received investigator-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work. MH has received investigator-initiated research funding from Gilead Sciences and AbbVie. JSD's institution has received investigator-initiated research funding from Gilead Sciences and AbbVie, and honoraria for speaking from Gilead Sciences and AbbVie. AP has received investigator-initiated research funding from Gilead Sciences and AbbVie, and honoraria for speaking duties from Gilead Sciences. RJW has received investigator-initiated research funding from Gilead Sciences. JAH has received honoraria for speaking duties from Gilead Sciences and AbbVie, as well as investigator-initiated research funding from Gilead Sciences, AbbVie, Cook Medical, and the Victorian Department of Health and Human Services. AJT has received consulting fees from Gilead, Abbvie, Roche, BMS, Merck, Immunocore, Janssen, Assembly Biosciences, Arbutus, Eisai, Ipsen and Bayer, speaker fees from Gilead Sciences, and investigator-initiated grants from Gilead Sciences., (Copyright © 2024. Published by Elsevier B.V.)

Background: Gay and bisexual men (GBM) have higher substance use prevalences than general population samples - often attributed to stigmatisation of sexual minority identities. We examined how influential public health research on substance use among GBM interprets this behaviour and what GBM-specific identities emerge through the discourses employed., Methods: We searched Web of Science for publications on substance use among GBM, selecting 60 of the most cited papers published during 2000-2020. We studied the language used to describe and interpret drug-using behaviour using critical discourse analysis, focusing on interpretive repertoires and subject positions., Results: Three distinct discursive tendencies were identified. First, in constructing a target population, GBM who use illicit drugs are positioned as deficient, socially irresponsible, and maladapted to dealing with stigmatisation and HIV risks. Second, in shifting the focus beyond the individual, the gay community is conceptualised as offering a safe space for socialisation. Nonetheless, gay community spaces are problematised as promoting substance use among vulnerable GBM through aggravating loneliness and normalising drug use as a form of maladaptive (avoidance) coping. Third, counterdiscursive movements add nuance, context, and comparisons that relativise rather than generalise substance use and focus on pleasure and self-determination. Such discourses centre the need for interventions that disrupt homophobic socio-structures instead of individualising approaches to limit non-conformity., Conclusion: 'Expert' assessments of substance use among GBM perpetuate pathologising understandings of this behaviour and promote abject subject positions, contributing to perpetuations of intergroup stigma and social exclusion based on drug and sexual practices. Our findings highlight the need for deliberate and critical engagement with prior research and a conscious effort to disrupt dominant discourses on GBM's substance use., Competing Interests: Declarations of Interest MH and AP receive investigator-initiated research funding from Gilead Sciences and AbbVie. JD's institution has received investigator-initiated research funding from Gilead and AbbVie and consultancies from Gilead and AbbVie. AP and her institution have received consultancies and travel honoraria from Gilead. AB's institution has received investigator-initiated research funding from ViiV. MS has received investigator-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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: Injecting drug use is purportedly more common among gay and bisexual men (GBM) than the general Australian population. Approaches designed to support the wellbeing of people who inject drugs may not be effective for GBM who inject, due to divergent settings, substances, and/or symbolism. We sought to identify the critical elements shaping injecting among GBM as a social practice and the implications for health and psychosocial wellbeing., Methods: We conducted 19 in-depth interviews with GBM in Australia with lifetime experience of injecting drug use, adopting the Frameworks Method for data analysis. Framed by social practice theory, transcripts were coded to delineate the constituent material, competency, and meaning elements of GBM's injecting practices. We developed themes encompassing the dynamic interrelationship between practice elements and wellbeing aspects., Results: Of 19 participants interviewed (aged 24-60 years), 17 identified as gay, two as bisexual. Injecting histories ranged from 2-32 years; most injected methamphetamine (n = 18). Injecting involved the integration of sexual function with substances and injecting skills in dyadic/communal settings. Beyond traditional harm reduction aspects, 'safe injecting' concerned trustworthiness of fellow practitioners, preventing addiction, and maintaining a solid self-concept. Injecting occurred as a dyadic/communal practice, in which an uneven distribution of materials (substances, sexual capital) and competencies (self-injecting) influenced risk and power dynamics. Pleasurable meanings of belonging, desirability and self-actualisation - gained from communities of practice - conflicted with injecting-related stigma, social dependencies, and fear of harms to body, mind, and sense of self., Conclusion: Injecting is a heterogenous practice, including among GBM. Shifting configurations of its composite elements influence GBM's perceptions and experiences of pleasure, risk, and harms. Efforts to support their wellbeing should take a dyadic/communal approach and seek to rectify the uneven distribution of material and competency elements in these settings., 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: Compared to other countries in sub-Saharan Africa, Tanzania has a relatively progressive illicit drug harm reduction (HR) policy, through a predominantly opioid substitution therapy-based programme. However, access to hepatitis C virus (HCV) diagnosis and curative direct acting antiviral therapy remains elusive. We developed a cost-effectiveness model to evaluate a simplified HCV screening-and-treatment intervention amongst PWID in Dar-es-Salaam, Tanzania., Methods: A decision tree and Markov state transition model compared existing practice (no access to HCV viral confirmation and treatment) with the integration of point-of-care HCV screening and treatment within (1) existing HR services and (2) expansion to include PWID not currently engaged in HR. Outcome measures were screening, treatment, HR and disease-related costs per PWID, quality-adjusted life years (QALY) and disability adjusted life years (DALY). Cost-effectiveness was evaluated from a healthcare payer's perspective over a 30-year time horizon over a range of willingness-to-pay thresholds (USD$273 to USD$1,050). Both deterministic and probabilistic sensitivity analyses have been conducted., Results: Assuming a chronic HCV prevalence of 18.8%, screening-and-treatment in existing HR settings resulted in an ICER per QALY-gained and DALY averted of USD$633 and USD$1,161, respectively. Expanding to include an outreach programme for unengaged PWID yielded an ICER per QALY-gained and DALY-averted of USD$4,091 and USD$10,288. Factors affecting the sensitivity of the ICER value included the cost of HR and the health utility of non-cirrhotic disease states., Conclusion: Simplified HCV screening and treatment of PWID has the potential to be cost-effective in Dar-es-Salaam, Tanzania. In practice, synergism of human and financial resources with established health programmes may offer a pragmatic solution to minimise operational costs., Competing Interests: Declarations of Interest All authors have no conflict of interest to declare in relation to this study., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Background: In Australia, the unrestricted and subsidised availability of direct-acting antivirals for people living with hepatitis C has made the elimination of hepatitis C possible. Recent declining treatment uptake, however, may jeopardise the attainment of this goal. Notification data already exist in many jurisdictions but are presently under-utilised. Despite growing interest in the potential use of data to link people diagnosed with hepatitis C to treatment services, little evidence exists on the acceptability and feasibility of this approach. Our study aimed to address this gap and guide future strategies to enhance treatment uptake., Methods: Twenty-seven people with lived experience of injecting drug use and/or hepatitis C participated in two focus groups exploring views on implementing a system of hepatitis C notification follow-up in Australia, that would direct people to treatment and care. Additionally, qualitative interviews were conducted with 20 key informants to examine the ethical, logistical, and regulatory implications of implementation. Data were thematically analysed using the Theoretical Framework of Acceptability - which has been used to assess the acceptability of interventions from the perspectives of intervention deliverers and recipients., Results: While there were clear reservations, there was consensus that the potential benefits of using notification data to contact people with hepatitis C, outweigh harms. The method of contact (including by whom and how), whether follow-up should include recent versus historical diagnoses, and if record linkage should be used to enhance follow-up were important considerations. Ethical and logistical concerns were raised about the risk that such an approach could exacerbate stigma and discrimination., Conclusion: Findings highlight potentially significant benefits of using notifications data to increase access to hepatitis C treatment, a novel approach that can contribute to hepatitis C elimination efforts and prevent hepatitis C-related morbidity and mortality., Competing Interests: Declarations of Interest The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hepatitis C is highly prevalent among prisoners. The simplicity of direct-acting antiviral (DAA) treatment for hepatitis C makes it possible to use novel models of care to increase treatment uptake within prisons. We estimate the average non-drug cost of initiating a prisoner on treatment using real world data from the State-wide Hepatitis Program (SHP) in Victoria, Australia - a coordinated nurse-led model of care., Methods: Data were considered from prisoners presenting to the SHP (following antibody-positive diagnosis) during the evaluation period, November 2015 to December 2016. All costs associated with the SHP were estimated, including staffing salaries, medical tests, pharmacy costs and overhead costs. DAA costs were excluded as in Australia an unlimited number are available, covered by a federal government risk-sharing agreement with pharmaceutical companies. The average non-drug cost of treatment initiation through the SHP was compared to equivalent costs from primary and hospital-based models of care in the community., Results: The total non-drug cost accumulated by prisoners in the SHP was AUD$749,470 (uncertainty range: AUD$728,905-794,111). 659/803 were PCR positive, 424/659 had sentences long enough to be eligible for treatment, and 416/424 were initiated on treatment, resulting in an average non-drug cost of AUD$1,802 (95% CI: AUD$1799-1841) per prisoner initiated. A protocol change allowing prisoners with short sentences to start treatment reduced the average non-drug cost to AUD$1263 (95% CI: AUD$1263-1287) per prisoner initiating treatment - 11% and 56% cheaper than estimated equivalent costs in primary (AUD$1654) and hospital-based (AUD$2847) models of care in the community, respectively., Conclusion: Delivering hepatitis C treatment in prison using a nurse-led model of care is cheaper than delivering treatment in the community. These findings provide an economic rationale for implementing coordinated prison-based hepatitis C treatment programs., Competing Interests: Declarations of Interest NS and APe have received investigator-initiated research funding from Gilead Sciences. AT is an advisory board member for Gilead Sciences, AbbVie, Bristol-Myers Squibb (BMS), Merck and Roche Diagnostics, and a speaker for Gilead, Merck, BMS, AbbVie, Roche Diagnostics. MH, APe, and the Burnet Institute receive investigator-initiated research funding from Gilead Sciences, Abbvie and BMS. TP and APe has received honoraria for speaking duties from Gilead Sciences. No pharmaceutical grants were received in the development of this study., (Copyright © 2021. Published by Elsevier B.V.)

Background: Hepatitis C (HCV) elimination strategies are required for low and middle-income countries (LMICs), because although treatment access is currently limited, this is unlikely to remain the case forever. We estimate and compare the impact, cost and cost-effectiveness of a variety of prevent, test and treat strategies for HCV in Dar es Salaam, Tanzania., Methods: A mathematical model., Results: Without intervention, the HCV epidemic in Dar es Salaam was estimated to result in US$29.1 million in disease costs between 2018 and 2030. Maintaining existing harm reduction coverage (4% needle and syringe program, 42% opioid substitution therapy) over this period was estimated to prevent 22% of injecting drug use-acquired HCV infections compared to a zero coverage scenario. Implementing antibody/RNA, serum-based HCV core antigen (HCVcAg) and dry blood spot (DBS) HCVcAg test/treat programs among PWID increased the total cost by US$0.7 million, US$3.1 million and US$6.5 million respectively by 2030; however this expenditure led to 57%, 61% and 73% reductions in annual incidence among PWID, 25%, 27% and 33% reductions overall annual incidence (PWID+non-PWID), and reduced HCV prevalence among PWID from 27% to 9%, 8% and 5%, respectively. The Ab/RNA, serum-based and DBS HCVcAg test/treat programs cost US$689, US$2857 and US$5400 per disability-adjusted life year averted, respectively, compared to no test/treat program., Conclusion: Primary prevention among PWID can provide important reductions in HCV transmission in the absence of treatment availability. HCV Ab/RNA or serum-based HCVcAg test/treat programs among PWID are likely to be cost-effective in Dar es Salaam, with serum-based HCVcAg test/treat achieving greater impact due to a simpler diagnostic process and better retention in care. If used for regular testing of PWID, the additional coverage benefits of non-laboratory-based DBS HCVcAg tests in LMICs would outweigh their reduced sensitivity., Competing Interests: Declaration of Interests NS has received investigator-initiated research funding from Gilead Sciences unrelated to this work. MH and the Burnet Institute receive investigator-initiated research funding from Gilead Sciences, AbbVie and BMS. ZM has received funding from Gilead Sciences. MH is the recipient of an Australian National Health and Medical Research Council fellowship. The authors gratefully acknowledge the support provided to the Burnet Institute by the Victorian Government Operational Infrastructure Support Program., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Little is known about how information on direct-acting antiviral treatment for hepatitis C circulates through peer networks of people who inject drugs. In this study we aimed to explore what and how treatment-related information is shared between people undergoing treatment and their peers., Methods: Participants were recruited from two general practice clinics and the community-based hepatitis C Treatment and Prevention Study. Semi-structured interviews were conducted with each participant (N = 20) before, during and following treatment. Interviews explored hepatitis C treatment experiences, key sources of DAA information and the impact of receiving and sharing knowledge. Inductive thematic analysis was conducted. Time sequential matrices were generated to understand thematic change over time., Results: Fifty-four interviews were conducted with 20 participants across seven field-sites in Melbourne, Australia. Key themes were: 'peers as a source treatment information', 'do it together' and 'becoming a treatment advocate'. Peers were a crucial trusted source of information. Positive treatment anecdotes were important for building confidence in and motivation to initiate treatment. Many participants adopted a 'treatment advocate' role in their close peer networks, which was described as empowering. Some participants described benefits of undertaking treatment alongside members of their close network., Conclusion: Findings illustrate the importance of close peers in shaping treatment perceptions and engagement. This will be important in designing health promotion messaging and interventions to increase treatment uptake., Competing Interests: Declaration of Interests SG and DH have no competing interests to declare. JD and MH have received investigator-initiated research funding to their institution from Gilead Sciences, Abbvie, Merck and Bristol Myers Squibb. JD's institution has received funding for consultancies from Gilead Sciences, Abbvie, and Merck. PH has received investigator-initiated research funding to his institution from Gilead Sciences and Abbvie., (Copyright © 2020. Published by Elsevier B.V.)

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST., Methods: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12)., Results: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed., Conclusion: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection., Methods: SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics., Results: Among 103 participants, 97% (n = 100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n = 33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥240 min) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P = 0.944)., Conclusion: This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Reliably measuring drug use by gay, bisexual and other men who have sex with men (GBM) in the context of sex can inform sexual health service responses. We report changing drug use patterns among GBM testing for HIV at a community-based service in Melbourne in response to behavioural survey modifications., Methods: Surveys were completed by GBM prior to all HIV tests. Survey one asked about use of "party drugs for the purpose of sex" and survey two asked about specific drug use (alcohol, amyl nitrate, methamphetamine, cocaine, ecstasy, GHB, Viagra ® /Cialis ® ) before or during sex. Differences in drug use prevalence and demographic and sexual risk correlates are reported., Results: Reported drug use increased from 16.9% in survey one to 54.0% in survey two. Among GBM completing both surveys, 45% who reported no drug use in survey one reported drug use in survey two. Drug use was associated with high HIV risk behaviours across both surveys., Conclusion: Survey modification improved ascertainment of drug use in the context of sex among GBM. Continued monitoring of drug use in this setting will improve our understanding the relationship between use of specific drugs and sexual health and help inform client focused health promotion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There are few data on treatment for hepatitis C virus (HCV) infection among people with ongoing injecting drug use. This study evaluated the efficacy of response-guided therapy for chronic HCV genotypes 2/3 infection among people with ongoing injecting drug use or receiving opioid substitution therapy (OST). A secondary aim was to identify predictors of HCV treatment response., Methods: ACTIVATE was a multicentre clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Participants were recruited from drug treatment clinics, private practices, hospital clinics and community clinics in Australia, Canada, and five countries in Europe. The primary study outcome was sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment)., Results: Among 93 people with ongoing injecting drug use or receiving OST treated for HCV genotype 2/3, 59% had recently (past month) injected drugs, 77% were receiving OST and 56% injected drugs during therapy. Overall SVR was 66% (61/93). SVR was 84% in those with undetectable HCV RNA at week 4 (12 weeks) compared to 38% in those without (24 weeks). In adjusted analysis, cirrhosis vs. no/mild fibrosis [adjusted OR (aOR) 0.33, 95% CI 0.13, 0.86] predicted reduced SVR, while response at week 4 was associated with increased SVR [aOR 8.11, 95% CI 2.73, 24.10]. Recent injecting drug use at baseline or during therapy was not associated with SVR., Conclusion: This study demonstrates that people with recent injecting drug use or OST with chronic HCV can achieve responses to interferon-based therapy similar to other populations, despite injecting drugs prior to or during therapy. Cirrhosis was predictive of reduced response to HCV therapy, while response at week 4 (despite shortened therapy) was predictive of improved response., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST)., Methods: ACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations., Results: Among 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83-0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89-1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79-1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70-1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92-1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40-0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07-2.04)., Conclusions: Recent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The hepatitis C virus (HCV) epidemic is a major health issue; in most developed countries it is driven by people who inject drugs (PWID). Injecting networks powerfully influence HCV transmission. In this paper we provide an overview of 10 years of research into injecting networks and HCV, culminating in a network-based approach to provision of direct-acting antiviral therapy., Methods: Between 2005 and 2010 we followed a cohort of 413 PWID, measuring HCV incidence, prevalence and injecting risk, including network-related factors. We developed an individual-based HCV transmission model, using it to simulate the spread of HCV through the empirical social network of PWID. In addition, we created an empirically grounded network model of injecting relationships using exponential random graph models (ERGMs), allowing simulation of realistic networks for investigating HCV treatment and intervention strategies. Our empirical work and modelling underpins the TAP Study, which is examining the feasibility of community-based treatment of PWID with DAAs., Results: We observed incidence rates of HCV primary infection and reinfection of 12.8 per 100 person-years (PY) (95%CI: 7.7-20.0) and 28.8 per 100 PY (95%CI: 15.0-55.4), respectively, and determined that HCV transmission clusters correlated with reported injecting relationships. Transmission modelling showed that the empirical network provided some protective effect, slowing HCV transmission compared to a fully connected, homogenous PWID population. Our ERGMs revealed that treating PWID and all their contacts was the most effective strategy and targeting treatment to infected PWID with the most contacts the least effective., Conclusion: Networks-based approaches greatly increase understanding of HCV transmission and will inform the implementation of treatment as prevention using DAAs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In high income countries, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). In many low and middle income countries large HCV epidemics have also emerged among PWID populations. The burden of HCV-related liver disease among PWID is increasing, but treatment uptake remains extremely low. There are a number of barriers to care which should be considered and systematically addressed, but should not exclude PWID from HCV treatment. The rapid development of interferon-free direct-acting antiviral (DAA) therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near optimal efficacy with well-tolerated, short duration, all oral regimens. Further, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provide a framework for HCV assessment and care. Further research is needed to evaluate strategies to enhance testing, linkage to care, treatment, adherence, viral cure, and prevent HCV reinfection among PWID, particularly as new interferon-free DAA treatments for HCV infection become available., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: A barrier to hepatitis C virus (HCV) treatment among people who inject drugs (PWID) has been a concern that interferon-based HCV treatment may increase injecting risk behaviours. This study evaluated recent (past month) injecting risk behaviours during follow-up among PWID that did and did not receive HCV treatment., Methods: The Australian Trial in Acute Hepatitis C (ATAHC) was a prospective study of natural history and treatment of recent HCV infection. Analyses were performed using generalized estimating equations., Results: Among 124 participants with a history of injecting drug use (median age 32 years), 69% were male, and 68% were treated for HCV infection. HCV treatment was not associated with an increase in recent injecting drug use (adjusted odds ratio (aOR) 1.06, 95% CI 0.93, 1.21) or recent used needle and syringe borrowing during follow-up (aOR 0.99, 95% CI 0.89, 1.08). HCV treatment was associated with a decrease in recent ancillary injecting equipment sharing during follow-up (aOR 0.85, 95% CI 0.74, 0.99). Further, among treated participants who remained in follow-up (n=24), ancillary injecting equipment sharing significantly decreased from 54% at enrolment to 17% during follow-up (P=0.012)., Conclusions: HCV treatment was not associated with drug use or used needle and syringe borrowing during follow-up, but was associated with decreased ancillary injecting equipment sharing during follow-up. Programs to enhance HCV assessment and treatment among PWID should be expanded, given that HCV treatment does not lead to increases in injecting risk behaviours and has previously been demonstrated to be safe and effective among PWID., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Young people who are same-sex attracted report higher rates of substance use, sexual risk behaviour, and mental health problems. Numerous studies have shown that sexual identity, sexual behaviour and sexual attraction do not always correspond, particularly among young people. We describe sexual identity, sexual partners, and associations between sexual identity and risk in a community-based sample of young people., Methods: From 2011 to 2013, young people (16-29 years) were recruited at a music festival in Melbourne, Australia to self-complete a questionnaire. We describe sexual identity and gender of anal/vaginal sex partners in the past year. Secondly, we assess associations between risk behaviours, health outcomes and gay/lesbian/bisexual/queer/questioning (GLBQQ)-identity using multivariable logistic regression., Results: Among 3793 (91%) participants with complete data, 115 (9%) males and 266 (11%) females were GLBQQ-identifying. Among GLBQQ-identifying males, 23% reported only same-sex partners, 34% reported both sex partners, 26% reported only opposite-sex partners, 5% reported no sex partners in the past year, and 12% had never had sex. Among GLBQQ-identifying females, 10% reported only same-sex partners, 22% reported both sex partners, 48% reported only opposite-sex partners, 3% reported no sex partners in the past year, and 17% had never had sex. Controlling for age and sex, significant (p<0.05) associations with GLBQQ-identity included: recent drug use (adjusted odds ratio [AOR] 1.7, 95%CI 1.3-2.2); ever injected drugs (AOR 5.7, 95%CI 3.3-9.7); young age at first sex (AOR 1.8, 95%CI 1.3-2.3); ≥11 lifetime sex partners (AOR 1.5, 95%CI 1.1-2.0); multiple sex partners in the past year (AOR 1.9, 95%CI 1.5-2.5); and rating mental health as fair/poor (AOR 3.0, 95%CI 1.9-4.6)., Conclusion: Young people with GLBQQ-identity commonly engage in high risk behaviours and are more at risk relative to their heterosexual-identifying peers. Targeted interventions to promote the health and wellbeing of this group should account for the complexities of identity and behaviour., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: People who inject drugs (PWID) are at risk of hepatitis C virus (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their injecting risk out of concern for their injecting partners, although evidence for this is currently limited. The aim of this study was to investigate whether informing PWID of their HCV diagnosis was associated with a change in injecting behaviour., Methods: Prospective, longitudinal study of PWID recruited from street drug markets across Melbourne, Australia. Interviews and HCV testing were conducted at 3-monthly intervals. The association between receiving a diagnosis of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was examined using generalized estimating equations (GEE) analysis., Results: Thirty-five individuals received a diagnosis of HCV during the study period. Receiving a diagnosis of HCV was associated with a decrease of 0.35 injections per month (p=0.046) but there was no change in injecting equipment borrowing (p=0.750)., Conclusions: A small reduction in injecting frequency was observed in PWID who received a diagnosis of HCV. This finding should be investigated further in larger studies examining a wider range of injecting risk behaviours., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: A systematic review was conducted to determine whether behavioural interventions are effective in preventing transmission of hepatitis C virus (HCV) amongst people who inject drugs., Methods: Medline, EMBASE, the Cochrane Clinical Trial Database, PSYCHINFO and hand-searching of bibliographies were used to identify controlled trials of behavioural interventions for reducing HCV transmission amongst people who inject drugs. Behavioural interventions were defined as non-pharmacological interventions that aimed to change individual behaviours without explicitly attempting to change population norms., Results: Six trials evaluating peer-education training and counselling interventions were included in the review. There was considerable variation between trials with respect to intervention duration, control and study population. Trials evaluated the impact of interventions on HCV incidence (three studies, 1041 participants) and frequency of injecting risk behaviours (six studies, 2472 participants). Amongst the three studies which measured the impact of the intervention on HCV incidence, none found a statistically significant difference between intervention and control groups. Measures of frequency of injecting risk behaviours varied greatly and could not be pooled. Only two studies (n=418, 854) showed significantly greater reductions in injecting risk behaviours in the intervention group compared with the control group., Conclusions: There was considerable variation in study design, outcome measures and magnitude, direction and statistical significance of findings between studies. Nonetheless, it is unlikely that behavioural interventions can have a considerable effect on HCV transmission. It is likely that multi-component interventions are required., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Evidence of harms associated with temazepam gel capsule injecting among injecting drug users in Australia led to its withdrawal from manufacture in Australia. Subsequently, diphenhydramine gel capsule injecting was identified among a subset of ethnic Vietnamese injecting drug users., Methods: Observational fieldwork around an active street-based illicit drug marketplace together with targeted purposive sampling enabled 66 ethnic Vietnamese injecting drug users to be recruited for in-depth interview., Results: Data revealed that the injection of gel capsules increases exposure to non-viral infections. Analysis of participant interviews show how participants have established their own ways of reducing these harms including thinning the drug solution by jacking regularly during injection. Controversially, femoral vein administration of diphenhydramine-heroin cocktails was also seen as a harm reduction strategy by participants., Discussion: Health education campaigns to address the potentially negative consequences of gel capsule groin injection will not be successful unless health workers and policy makers work with drug users and incorporate local understandings and meanings of risk in health promotion activities.

The hepatitis C virus (HCV) affects over 170 million people worldwide. In Australia, over 225,000 people have been diagnosed with HCV infection with 13,000 infections reported annually; 90% are attributed to injecting drug use. Burnet Institute (BI) researchers have been studying the HCV epidemic since the virus was identified in 1989 including community based cohort studies (1990-1995), numerous studies involving Vietnamese-Australian people who inject drugs (PWID) (1996-2004) and social network studies (2000-2002, 2005-2007). Through this work the BI has developed a model of research practice for HCV and PWID, developed in recognition that much research relating to BBV infections - and HCV in particular - could be improved in terms of provision of test results to study participants. Our model endeavours to provide all participants with the highest quality HCV test results, delivered in accordance with best practice for pre- and post-test counselling by engaging participants in environments in which they are comfortable, building trust and rapport and being available throughout and beyond the research study. This paper will discuss the benefits and lessons learned over numerous studies in providing pre- and post-test counselling to PWID in an outreach capacity.