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Introduction: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex‐specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. Methods: HCV notifications in New South Wales, Australia (1995–2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016–2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18–44), including those with recent drug dependence. Results: Among 57,467 people with evidence of chronic HCV in the DAA era (2016–2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18–44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Conclusion: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination. [ABSTRACT FROM AUTHOR]

Introduction: Studies of health utilities among people who use opioids have mostly been based on in‐treatment populations. We aim to report utility‐based quality of life by participants' socio‐demographic, drug and treatment characteristics, and to examine the determinants of health utility among people who use opioids regularly. Methods: Cross‐sectional study of participants who used opioids regularly, recruited across New South Wales, Victoria and Tasmania in 2018–2019. Differences in European Quality of Life (EQ‐5D‐5L) heath utility scores between socio‐demographic and clinical subgroups were assessed using non‐parametric Kruskal–Wallis test by rank. To address the unique distribution of EQ‐5D‐5L health utility scores in the current sample, a two‐part model was applied to assess factors associated with health utility. Results: Among 402 participants enrolled in the study, 385 (96%) completed the EQ‐5D‐5L questionnaire. The mean health utility of the total sample was 0.63 (SD 0.29). Participants who previously received opioid agonist treatment [OAT] (adj marginal effect (ME) −0.11; 95% confidence interval [CI] −0.20 to −0.02) and those currently in OAT (adj ME −0.13; 95% CI −0.22 to −0.06) reported lower health utility than those who had never received OAT. Participants who used both pharmaceutical opioids and benzodiazepines had lower health utility compared to no pharmaceutical opioids and no benzodiazepines use (adj ME −0.17; 95% CI −0.28 to −0.07). Discussion and Conclusions: Findings provide important health utility data for economic evaluations, useful for guiding allocation of resources for treatment strategies among people who use opioids. Lower health utilities among those using benzodiazepines and pharmaceutical opioids suggests interventions targeting these subgroups may be beneficial. [ABSTRACT FROM AUTHOR]

Background The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings. Methods A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021–2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021–2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed. Results Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community. Conclusions Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy. Clinical Trials Registration NCT02064049. [ABSTRACT FROM AUTHOR]

Background: Dried blood spot (DBS) testing provides an alternative to phlebotomy and addresses barriers to accessing healthcare experienced by some key populations. Large-scale evaluations of DBS testing programs are needed to understand their feasibility. This study evaluated the implementation of a state-wide DBS HIV and hepatitis C virus (HCV) testing pilot. Methods: The New South Wales (NSW) DBS Pilot is an interventional cohort study of people testing for HIV antibody and/or HCV RNA from DBS samples in NSW, Australia. Participants at risk of HIV/HCV participated in testing via: 1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or 2) assisted DBS sample collection at 36 community health sites (including drug treatment and harm-minimisation services) and prisons. Participants received results by text (HIV antibody/ HCV RNA not detected) or a healthcare provider (HIV antibody/ HCV RNA detected). The RE-AIM framework was used to evaluate reach, effectiveness, adoption, and implementation. Results: Reach: Between November 2016 and December 2020, 7,392 individuals were tested for HIV and/or HCV (21% self-registration, 34% assisted in community, and 45% assisted in prison). Effectiveness: Of 6,922 people tested for HIV (19% men who have sex with men, 13% living outside major cities, 21% born outside Australia), 51% (3,521/6,922) had no HIV test in the past two years, 0.1% (10/6,922) were newly diagnosed with HIV, and 80% (8/10) initiated HIV treatment within six months. Of 5,960 people tested for HCV (24% women, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs), 15% had detectable HCV RNA (878/5,960), and 45% (393/878) initiated treatment within six months. Adoption: By the end of 2020, DBS via assisted registration was available at 36 community sites and 21 prisons. Implementation: 90% of DBS cards arriving at the laboratory had the three full spots required for testing; the proportion was higher in assisted (94%) compared to online (76%) registration. Conclusions: This study demonstrated the feasibility of DBS testing for HIV and HCV in key populations including Aboriginal and Torres Strait Islander peoples, men who have sex with men, people who inject drugs, and demonstrated the utility of DBS in the prison setting. [ABSTRACT FROM AUTHOR]

Background Dried blood spot (DBS) testing for hepatitis C virus (HCV) RNA provides a sampling option that avoids venepuncture and can be carried out in a nonclinical setting. Large-scale evaluations are needed to understand how DBS testing can reduce HCV burden. This study estimated prevalence of, and factors associated with, HCV RNA and treatment initiation among people enrolled in a state-wide pilot of people testing in the NSW DBS Pilot in New South Wales, Australia. Methods People at risk of HIV/HCV could participate via (1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or (2) assisted DBS sample collection at a community site or prison. Logistic regression was used to identify factors associated with detectable HCV RNA and treatment initiation within 6 months of testing. Results Between September 2017 and December 2020, 5960 people were tested for HCV (76% men, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs): 21% online self-registration, 34% assisted registration in the community, 45% assisted registration in prison. Fifteen percent had detectable HCV RNA (878/5960). Overall, 44% (n = 386/878) of people with current HCV initiated treatment within 6 months (13% online self-registration, 27% assisted registration in the community, 61% assisted registration in prison). Testing in prison compared with the community (adjusted odds ratio [aOR], 4.28; 95% CI, 3.04–6.03) was associated with increased odds of treatment initiation. Being a woman compared with a man (aOR, 0.68; 95% CI, 0.47–0.97) was associated with reduced treatment initiation. Conclusions The NSW DBS Pilot demonstrates the feasibility of using DBS to promote HCV testing and treatment in community and prison settings. [ABSTRACT FROM AUTHOR]

Background & Aims: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison‐based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. Methods: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020–2029. We estimated the past and potential future impact of prison‐based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%–83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison‐based interventions. Results: Over 2020–2029, incarceration will contribute 23.0% (17.9–30.5) of new HCV infections. If prison‐based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4–36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison‐based interventions. Conclusions: Existing prison‐based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison‐based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) care cascade characterization is important for monitoring progress towards HCV elimination. This study evaluated HCV care cascade and factors associated with treatment during pre‐DAA (2011–2012 and 2013–2015) and DAA (2016–2018) eras in New South Wales (NSW), Australia. We conducted a cohort study of people with an HCV notification (1993 to 2017) through end 2018, linked to administrative datasets, including HCV treatment and non‐hospital services. Those aged <18 years, died within first 6 months of study period or notification, and who had successful HCV treatment in period before were excluded. Sex‐specific spontaneous viral clearance was incorporated to estimate treatment‐eligible population. The study population in each period were cumulative and brought forward from one period to the next. Among 115,667 people with HCV notification, 87,063 fulfilled eligibility criteria. During 2011 to 2012, 2013 to 2015, and 2016 to 2018, cumulative HCV notifications were 71,677, 77,969, and 80,017; 52,016, 56,793, and 57,467 were eligible for treatment; 29%, 48%, and 64% confirmed HCV RNA positive; and 0.6%, 5%, and 38% initiated HCV treatment, respectively. Birth cohort 1945 to 1964 (vs. ≥1965), males, non‐Aboriginal ethnicity, regional/rural area of residence, and HCV/HIV co‐infection were associated with higher treatment uptake. Incarceration and drug dependence were associated with higher treatment uptake during the DAA era. In Australia, many marginalized populations including those incarcerated and those with drug dependence have equitable treatment uptake in the DAA era. Targeted strategies are required to enhance treatment uptake for females and Aboriginal populations. [ABSTRACT FROM AUTHOR]

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many. [ABSTRACT FROM AUTHOR]

Background People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. Methods We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016–December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. Results Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. Conclusions Among people who have evidence of recent drug dependence, frequent hospitalization—particularly mental health, drug, and alcohol admissions—presents an opportunity for engagement in HCV care. [ABSTRACT FROM AUTHOR]

Abstract: Background: Internationally, there are ongoing efforts to increase access to hepatitis C (HCV) assessment and treatment to counter a generally low uptake of treatment among people with a history of injecting drug use. The aim of this qualitative study was to examine client and staff attitudes towards and experience of co-location of HCV and opioid substitution treatment (OST) services. Methods: In-depth interviews were conducted with 57 clients and 19 staff from four NSW clinics participating in the Australian ETHOS study. Results: Client and staff participants typically welcomed integrated treatment, citing issues of convenience, reduced travel time and costs, persistent cues to engagement and immediacy of access to care. Positive attitudes towards the initiative were expressed even by clients who had not engaged with HCV care. Providing co-located care largely avoided the negative, stigmatising or discriminatory experiences that participants reported encountering in settings less familiar with people who use drugs. A minority of client participants expressed concerns about the lack of privacy and/or confidentiality available in the co-located model, preferring to seek HCV care elsewhere. Conclusions: The co-location of HCV care in OST clinics was welcomed by the large majority of participants in this study. Besides issues of convenience, the appeal of the co-located service centred on the familiarity of existing relationships between clients and staff in the OST setting. While some clients remained distrustful of OST and chose not to take up HCV care in this setting, the co-located treatment model was overwhelmingly successful amongst both client and staff participants. [Copyright &y& Elsevier]

High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98). These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced. • People who inject drugs are a key population for hepatitis C elimination. • Australia has provided universal access to direct-acting antiviral therapy since 2016. • Data linkage was used to assess population-level direct-acting antiviral uptake. • Those with evidence of recent drug dependence had the highest treatment uptake. • Despite higher direct-acting antiviral uptake among those with recent drug dependence, gaps remain. [ABSTRACT FROM AUTHOR]

Transitional times in opioid use, such as release from prison and discontinuation of opioid agonist treatment (OAT), are associated with health harms due to changing drug consumption practices and limited access to health and social supports. Using a self-controlled (within-person) study design, we aimed to understand if these transitions increase risks of injection drug use-associated bacterial infections. We performed a self-controlled case series among a cohort of people with opioid use disorder (who had all previously accessed OAT) in New South Wales, Australia, 2001-2018. The outcome was hospitalisation with injecting-related bacterial infections. We divided participants' observed days into time windows related to incarceration and OAT receipt. We compared hospitalization rates during focal (exposure) windows and referent (control) windows (i.e., 5-52 weeks continuously not incarcerated or continuously receiving OAT). We estimated adjusted incidence rate ratios (aIRR) using conditional logistic regression, adjusted for time-varying confounders. There were 7590 participants who experienced hospitalisation with injecting-related bacterial infections (35% female; median age 38 years; 78% hospitalised with skin and soft-tissue infections). Risk for injecting-related bacterial infections was elevated for two weeks following release from prison (aIRR 1.45; 95%CI 1.22–1.72). Risk was increased during two weeks before (aIRR 1.89; 95%CI 1.59–2.25) and after (aIRR 1.91; 95%CI 1.54–2.36) discontinuation of OAT, and during two weeks before (aIRR 3.63; 95%CI 3.13–4.22) and after (aIRR 2.52; 95%CI 2.09–3.04) OAT initiation. Risk of injecting-related bacterial infections varies greatly within-individuals over time. Risk is raised immediately after prison release, and around initiation and discontinuation of OAT. Social contextual factors likely contribute to excess risks at transitions in incarceration and OAT exposure. [ABSTRACT FROM AUTHOR]

• Prior to the introduction of DAA therapy, the disease burden of HCV was rising in New South Wales. • DAA scale-up has had a major population-level impact on HCV morbidity and mortality. • The World Health Organization has set a 65% HCV mortality reduction target by 2030. • To achieve this target, enhanced efforts are required to continue DAA scale-up. • In the DAA era, the impact of heavy alcohol use on liver disease should be monitored. Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001–2014) and DAA therapy (2015–2017) eras in New South Wales, Australia. HCV notifications (1993–2016) were linked to hospital admissions (2001–2017) and mortality (1995–2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04–1.05], 1.08 [95% CI 1.07–1.08], 1.07 [95% CI 1.06–1.07], and 1.05 [95% CI 1.04–1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95–0.99] and 0.96 [95% CI 0.94–0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97–1.03] and 1.01 [95% CI 1.00–1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14–3.58). In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C. [ABSTRACT FROM AUTHOR]

Abstract: Background: Assessment and uptake of treatment for hepatitis C among people who inject drugs (PWID) is low and strategies to enhance hepatitis C care in this group are needed. Knowledge of hepatitis C and its treatment is one precursor to decisions about treatment. Methods: We conducted a cross-section study designed to evaluate treatment considerations in participants with self-reported hepatitis C infection in New South Wales, Australia. Participants were recruited from needle and syringe programs, opiate substitution clinics, pharmacies that dispensed opiate substitution treatment and from the mailing list of a community-based hepatitis C organisation and completed a self-administered survey. Knowledge of hepatitis C was assessed by a 48-item scale addressing the natural history and treatment of hepatitis C. Factors associated with knowledge were assessed by ordinal regression. Results: Among the 997 participants recruited, 407 self-reported acquiring hepatitis C through injecting drug use and had never received hepatitis C treatment. Knowledge about hepatitis C was overall poor and the effects of the long term consequences of hepatitis C were over-estimated. Higher knowledge scores were associated with recruitment site, higher education levels and recent contact with a general practitioner. One-third of participants indicated that they did not intend to have treatment and one-fifth did not answer this question. Conclusion: Knowledge is a precursor to informed decisions about hepatitis C treatment. These results indicate that efforts to support those less engaged with hepatitis C care (and specifically those on opiate substitution treatment) and those with lower literacy are required. [Copyright &y& Elsevier]

Background: Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting., Methods: SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two maximum-security prisons (male) and two medium-security prisons (one male, one female) in New South Wales, Australia. All prison inmates aged at least 18 years were eligible for enrolment. After HCV testing, participants were monitored for risk behaviours and HCV infection, among three sub-populations: uninfected (HCV antibody-negative); previously infected (HCV antibody-positive, HCV RNA-negative); and infected (HCV antibody and HCV RNA-positive). Uninfected participants were followed up every 3-6 months to detect HCV primary infection and previously infected participants were followed up every 3-6 months to detect re-infection. Participants with HCV infection were assessed for treatment, initially standard-of-care treatment (administered by prison health services) from 2014 to mid-2017, then direct-acting antiviral (DAA) treatment scale-up from mid-2017 onwards (12 weeks of sofosbuvir plus velpatasvir, administered through SToP-C). Participants were followed up until study closure in November, 2019. The primary study outcome was HCV incidence before and after DAA treatment scale-up among participants at risk of HCV primary infection or re-infection. This study is registered with ClinicalTrials.gov, NCT02064049., Findings: Between Oct 30, 2014, and Sept 30, 2019, 3691 participants were enrolled in the SToP-C study. 719 (19%) participants had detectable HCV RNA, 2240 (61%) were at risk of primary HCV infection, and 725 (20%) were at risk of re-infection at baseline. DAA treatment was initiated in 349 (70%) of 499 eligible participants during the treatment scale-up period. The HCV incidence analysis comprised 1643 participants at risk of HCV infection or re-infection during longitudinal follow-up (median age 33 years [IQR 27-42]; 1350 [82%] male). 487 (30%) of 1643 participants reported injecting drugs in prison. HCV incidence decreased from 8·31 per 100 person-years in the pre-treatment scale-up period to 4·35 per 100 person-years in the post-treatment scale-up period (incidence rate ratio [IRR] 0·52 [95% CI 0·36-0·78]; p=0·0007). The incidence of primary infection decreased from 6·64 per 100 person-years in the pre-treatment scale-up period to 2·85 per 100 person-years in the post-treatment scale-up period (IRR 0·43 [95% CI 0·25-0·74]; p=0·0019), whereas the incidence of re-infection decreased from 12·36 per 100 person-years to 7·27 per 100 person-years (0·59 [0·35-1·00]; p=0·050). Among participants reporting injecting drugs during their current imprisonment, the incidence of primary infection decreased from 39·08 per 100 person-years in the pre-treatment scale-up period to 14·03 per 100 person-years in the post-treatment scale-up period (IRR 0·36 [95% CI 0·16-0·80]; p=0·0091), and the incidence of re-infection decreased from 15·26 per 100 person-years to 9·34 per 100 person-years (0·61 [0·34-1·09]; p=0·093). The adjusted analysis (adjusted for age, Indigenous Australian ethnicity, duration of stay in prison, previous imprisonment, injecting drug use status, and prison site) indicated a significant reduction in the risk of HCV infection between the pre-DAA treatment scale-up and post-DAA treatment scale-up periods (adjusted hazard ratio 0·50 [95% CI 0·33-0·76]; p=0·0014)., Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of a beneficial effect of HCV treatment-as-prevention in this setting. These findings support broad DAA treatment scale-up within incarcerated populations., Funding: Australian National Health and Medical Research Council Partnership Project Grant and Gilead Sciences., Competing Interests: Declaration of interests GJD is a consultant and adviser for, and has received research grants from, Gilead, AbbVie, Merck, Bristol-Myers Squibb, and Cepheid. ARL is a consultant and adviser for, and has received investigator-initiated research grants from, Gilead, Merck, and Bristol-Myers Squibb. JG is a consultant and adviser for, and has received research grants from, Gilead, AbbVie, Merck, and Cepheid. PV has received investigator-initiated untied grants from Gilead and honorarium from Gilead and Merck. NKM has received unrestricted research grants from Gilead and Merck. JGMc is a stockholder and ex-employee of Gilead Sciences. DMB is a stockholder and employee of Gilead Sciences. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Opioid agonist treatment is effective for opioid dependence and newer extended-release buprenorphine (BUP-XR) injections represent a significant development. The Community Long-Acting Buprenorphine (CoLAB) study aims to evaluate client outcomes among people with opioid dependence receiving 48 weeks of BUP-XR treatment, and examines the implementation of BUP-XR in diverse community healthcare settings in Australia., Methods and Analysis: The CoLAB study is a prospective single-arm, multicentre, open-label trial of monthly BUP-XR injections in people with opioid dependence. Participants are being recruited from a network of general practitioner and specialist drug treatment services located in the states of New South Wales, Victoria and South Australia in Australia. Following a minimum 7 days on 8-32 mg of sublingual buprenorphine (±naloxone), participants will receive monthly subcutaneous BUP-XR injections administered by a healthcare practitioner at intervals of 28 days (-2/+14 days). The primary endpoint is participant retention in treatment at 48 weeks after treatment initiation. Secondary endpoints will evaluate dosing schedule variations, craving, withdrawal, substance use, health and well-being, and client-reported treatment experience. Qualitative and costing substudies will examine implementation barriers and facilitators at the client and provider level., Ethics and Dissemination: The study has received ethics approval from the St Vincent's Hospital Sydney Human Research Ethics Committee (Ref. HREC/18/SVH/221). The findings will be disseminated via publication in peer-reviewed journals, presentations at national and international scientific conferences, and in relevant community organisation publications and forums., Trial Registration Number: NCT03809143 PROTOCOL IDENTIFIER: CoLAB1801, V.4.0 dated 01 August 2019., Competing Interests: Competing interests: Many of the investigators have received investigator-initiated, untied educational grants for opioid-related studies from: Indivior (Briony Larance, Louisa Degenhardt, Nicholas Lintzeris, Michael Farrell, Suzanne Neilsen); Reckitt Benckiser (Briony Larance, Louisa Degenhardt, Nicholas Lintzeris, Michael Farrell, Suzanne Nielsen, Robert Ali, Adrian Dunlop); Mundipharma (Briony Larance, Louisa Degenhardt, Nicholas Lintzeris, Michael Farrell); and Seqirus (Briony Larance, Louisa Degenhardt, Michael Farrell, Suzanne Nielsen)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hepatitis C (HCV) infection is highly prevalent within the prison setting. Direct-acting antiviral (DAA) therapies have changed the HCV treatment landscape, offering simple treatment (with minimal side-effects) and high efficacy. These advances have enabled the first real-world study of HCV treatment as prevention (TasP), the Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study. This paper draws on data from qualitative interviews completed with SToP-C participants following prison-wide DAA treatment scale-up., Methods: Semi-structured interviews were undertaken with 23 men in prison following HCV treatment completion to identify ongoing risk practices, perceptions of strategies for HCV prevention within the prison setting, experiences of HCV treatment (as prevention), and perceptions of reinfection following cure. Analysis was undertaken using a counterpublic health lens to identify risks and perceptions of reinfection among people treated for HCV within the prison setting., Results: Participants identified a number of challenges of meaningful HCV 'cure' in the absence of increased access to prevention strategies (e.g., opioid agonist therapy and prison needle syringe programs) along with concerns that 'cure' was only temporary whilst incarcerated. 'Cure' status included self-perceptions of being "clean", while also imposing responsibility on the individual to maintain their 'cure' status., Conclusion: HCV DAA treatment is provided somewhat under the guise of 'cure is easy', but fails to address the ongoing risk factors experienced by people who inject drugs in prisons, as well as other people in prison who may be at risk of blood-to-blood exposure. Health messaging regarding HCV treatment and treatment for reinfection should be tailored to ensure patient-centred care. Health interventions in prison must address the whole person and the circumstances in which they live, not just the illness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia., Methods: Notifications 1993-2012 were linked to cause-specific mortality records 1993-2013., Results: Among 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P < 0.001); however, HCV-related rates remained stable (0.2 to 0.3 per 100 PY, P = 0.619). In adjusted analyses, older age was the strongest predictor of liver-related mortality [birth earlier than 1945, HBV adjusted hazard ratio (aHR) 28.1, 95% CI 21.0, 37.5 and; HCV aHR 31.9, 95% CI 26.8, 37.9], followed by history of alcohol-use disorder (HBV aHR 7.0, 95% CI 5.5, 8.8 and; HCV aHR 8.3, 95% CI 7.6, 9.1)., Conclusions: Declining HBV-related liver mortality rates and stable burden suggest an impact of improved antiviral therapy efficacy and uptake. In contrast, the impact of interferon-containing HCV treatment programs on liver-related mortality individual-level risk and population-level burden has been limited. These findings also highlight the importance of HBV/HCV public health interventions that incorporate increased antiviral therapy uptake, and action on health risk behaviors.

Background: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use., Methods: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression., Results: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment., Conclusions: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background & Aims: People living with hepatitis C virus (HCV) are at increased risk of all-cause and liver-related mortality, although successful treatment has been shown to reduce this risk. The aim of this study was to provide baseline data on trends in cause-specific mortality and to establish an international surveillance system for evaluating the population level impact of HCV treatments., Methods: Population level HCV diagnosis databases from Scotland (1997-2010), Australia (New South Wales [NSW]) (1997-2006), and Canada (British Columbia [BC]) (1997-2003) were linked to corresponding death registries using record linkage. For each region, age-adjusted cause-specific mortality rates were calculated, and trends in annual age-adjusted liver-related mortality were plotted., Results: Of 105,138 individuals diagnosed with HCV (21,810 in Scotland, 58,484 in NSW, and 24,844 in BC), there were 7275 deaths (2572 in Scotland, 2655 in NSW, and 2048 in BC). Liver-related deaths accounted for 26% of deaths in Scotland, 21% in NSW, and 22% in BC. Temporal trends in age-adjusted liver related mortality were stable in Scotland (males p=0.4; females p=0.2) and NSW (males p=0.9; females p=0.9), while there was an increase in BC (males p=0.002; females p=0.04)., Conclusions: The risk of liver-related mortality after a diagnosis of HCV has remained stable or increased over time across three regions with well-established diagnosis databases, highlighting that HCV treatment programmes to-date have had minimal impact on population level HCV-related liver disease. With more effective therapies on the horizon, and greater uptake of treatment anticipated, the potential of future therapeutic strategies to reduce HCV-related mortality is considerable., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Access to hepatitis C virus (HCV) treatment remains extremely limited among people who inject drugs (PWID). HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection., Methods: Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment was through 5 opioid substitution treatment (OST) clinics, 2 community health centers, and 1 Aboriginal community controlled health organization in New South Wales, Australia., Results: Among 387 enrolled participants, mean age was 41 years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based treatment. In adjusted analysis, HCV specialist assessment was associated with non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31-3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59; 95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15; 95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR, 3.07; 95% CI, 1.67-5.64)., Conclusions: HCV treatment uptake was relatively high among this highly marginalized population of PWID. Potentially modifiable factors associated with treatment include drug use and social support.

Introduction and Aims: Uptake of treatment for hepatitis C virus (HCV) infection among people who inject drugs is low. Further understanding is required of the relationship between HCV knowledge and treatment willingness, assessment and treatment in this population., Design and Methods: A cross-sectional self-administered survey was conducted with clients of four opioid substitution therapy (OST) clinics and the Medically Supervised Injecting Centre in Sydney, Australia., Results: Of 132 participants, 85 (64%) self-reported having HCV infection. HCV knowledge was mixed (mean 6.5, range 0-12) and was relatively lower on items measuring knowledge of factors impacting HCV-related disease progression. The likelihood of being in a higher knowledge category was associated with being female [adjusted odds ratio (AOR) = 3.78, 95% confidence interval (CI) (1.79, 7.98)], higher formal education [AOR = 3.28, 95% CI (1.57, 6.88)], being on a current OST program [AOR = 2.61, 95% CI (1.10, 6.19)] and being older [AOR = 1.04, 95% CI (1.01, 1.09)]. Participants receiving OST were more likely to report higher willingness to have HCV treatment [OR = 4.45, 95% CI (2.23, 8.17)]. Having been assessed for HCV treatment was associated with younger age [AOR = 0.93; CI 95% (0.88, 1.00)] and higher formal education [AOR = 7.81; 95% CI (1.62, 37.71)]., Discussion and Conclusions: Overall, knowledge scores were mid-range. Knowledge of modifiable factors influencing HCV-related liver disease progression was particularly low indicating the need for ongoing education. Education should also be targeted at older people and those not on OST, and be inclusive of those with lower literacy levels., (© 2012 Australasian Professional Society on Alcohol and other Drugs.)