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BackgroundWhile opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT.MethodsIndependent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses.ResultsAmong 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P < .001).ConclusionsFemale PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.

Background and Aims: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct‐acting antiviral (DAA) treatment outcome in prisons. Methods: The Surveillance and Treatment of Prisoners with hepatitis C (SToP‐C) study enrolled individuals incarcerated in four Australian prisons (2017–2019). Participants with detectable HCV RNA were offered sofosbuvir‐velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention‐to‐treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per‐protocol (PP; participants with documented treatment completion and SVR assessment) populations. Results: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59–70]), and 137 achieved SVR (ITT‐SVR: 44% [95% CI: 39–50]). In PP population (n = 143), 137 achieved SVR (PP‐SVR: 96% [95% CI: 91–98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter‐prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01–1.04]). Conclusion: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non‐prison clinical studies. However, most individuals did not complete treatment or lacked study‐documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post‐treatment care. [ABSTRACT FROM AUTHOR]

Background:The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative). Methods:HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure. Results:A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15-1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors. Conclusions:Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs.

Combining phylogenetic and network methodologies has the potential to better inform targeted interventions to prevent and treat infectious diseases. This study reconstructed a molecular transmission network for people with recent hepatitis C virus (HCV) infection and modelled the impact of targeting directly acting antiviral (DAA) treatment for HCV in the network. Participants were selected from three Australian studies of recent HCV from 2004 to 2014. HCV sequence data (Core-E2) from participants at the time of recent HCV detection were analysed to infer a network by connecting pairs of sequences whose divergence was ≤.03 substitutions/site. Logistic regression was used to identify factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co-infected and random nodes was simulated (1 million replicates). Among 236 participants, 21% (n=49) were connected in the network. HCV/HIV co-infected participants (47%) were more likely to be connected compared to HCV mono-infected participants (16%) (OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV treatment to HCV/HIV co-infected individuals prevented 2.5 times more onward infections than providing DAAs to randomly selected individuals. Results demonstrate that genetic distance-based network analyses can be used to identify characteristics associated with HCV transmission, informing targeted prevention and treatment strategies.

BackgroundWe determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne).MethodsUsing population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk.ResultsAmong 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model.ConclusionsDifferences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America.

BackgroundApproximately one quarter of persons exposed to hepatitis C virus (HCV) will spontaneously clear infection. We undertook this study to investigate the impact of alcohol on likelihood of HCV spontaneous viral clearance stratified by sex groups.MethodsPooled data from an international collaboration of prospective observational studies of incident HIV and HCV infection in high-risk cohorts (the InC3 Study) was restricted to 411 persons (or 560.7 person-years of observation) with documented acute HCV infection and data regarding alcohol use. The predictor of interest was self-reported alcohol use at or after estimated date of incident HCV infection and the outcome was HCV spontaneous clearance. Sex stratified Cox proportional hazards models were used to evaluate the association between alcohol and spontaneous clearance, adjusting for age, race/ethnicity, and IFNL4 genotype.ResultsThe median age was 28.5 years, 30.4% were women, 87.2% were white, and 71.8% reported alcohol use at or after incident infection. There were 89 (21.6%) cases of spontaneous clearance observed, 39 (31.2%) among women and 50 (17.5%) in men (p

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]

Symptomatic acute HCV infection and interferon lambda 4 (IFNL4) genotypes are important predictors of spontaneous viral clearance. Using data from a multicohort database (Injecting Cohorts [InC3] Collaborative), we establish an independent association between host IFNL4 genotype and symptoms of acute hepatitis C virus infection. This association potentially explains the higher spontaneous clearance observed in some patients with symptomatic disease.

Introduction: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre‐exposure prophylaxis (PrEP) in Taiwan. Methods: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022–2030. Results: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person‐years among MSM by 2030. Single‐visit point‐of‐care RNA testing had the largest impact on reducing the number of new HCV infections over 2022–2030, with a 31.1% reduction (interquartile range: 24.9%−32.8%). By 2030, single‐visit point‐of‐care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point‐of‐care testing scenario. Conclusions: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single‐visit point‐of‐care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk‐reduction strategies will need to be implemented alongside point‐of‐care testing to achieve HCV elimination among MSM in Taiwan. [ABSTRACT FROM AUTHOR]

Introduction: Understanding needle/syringe sharing is crucial for reducing hepatitis C virus (HCV) infection and reinfection. This study aimed to assess the prevalence and factors associated with needle/syringe sharing among people who inject drugs in Australia, including those previously receiving HCV treatment. Methods: The ETHOS Engage study was an observational cohort study which collected self‐reported survey data on demographic and drug use information from people who inject drugs attending drug treatment clinics and needle and syringe programs over two waves between May 2018 and June 2021. Logistic regression was used to identify factors associated with needle/syringe sharing. Results: Overall, 1555/2395 people enrolled in ETHOS Engage (65%) injected drugs in the past month. Among these, 432 (28%) reported needle/syringe sharing in the past month and 276 (18%) reported receptive sharing. Factors associated with receptive sharing included younger age (adjusted odds ratio [aOR] 1.72; 95% confidence interval [CI] 1.28–2.30), recent incarceration (aOR 2.04; 95% CI 1.40–2.94), more frequent injecting (≥daily vs. less than weekly; aOR 2.59; 95% CI 1.75–3.84) and unstable housing (aOR 1.78; 95% CI 1.26–2.52). Among 560 participants with prior HCV treatment, 87 (16%) reported receptive sharing with younger age (aOR 2.42; 95% CI 1.45–4.05) and daily or greater injection frequency (aOR 2.51; 95% CI 1.31–4.83) associated with receptive sharing. Discussion and Conclusions: Needle/syringe sharing was common among this population accessing harm reduction services. This study identifies high‐risk populations with needle/syringe sharing. Research is needed to optimise HCV treatment to ensure people with ongoing risk behaviours receive adequate harm reduction following treatment to prevent reinfection. [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]

In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37–10.63), vitality (MTD, 6.81; 95% CI, 1.88–11.75), and mental health (MTD, 5.17; 95% CI, 0.52–9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29–5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL. ClinicalTrials.gov, NCT02251990 [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis C virus (HCV) is highly prevalent within the prison setting. Although HCV testing and treatment are available within prisons, system barriers can impede progress along the HCV care cascade for those who are incarcerated. The PIVOT intervention used a 'one‐stop‐shop' model (i.e. point‐of‐care HCV RNA testing, Fibroscan‐based liver disease assessment and treatment) at a reception prison in New South Wales, Australia. This analysis sought to understand the role of point‐of‐care HCV RNA testing at intake in reducing barriers to the HCV care cascade within the male prison setting. Design and Setting: Qualitative analysis using semi‐structured interviews in a reception prison in Australia. Participants: Twenty‐four men enrolled in the PIVOT study; all participants had undergone HCV point‐of‐care testing in the intervention arm. Measurements: Høj's Integrated Framework informed this analysis. Findings: Participants widely expressed the view that point‐of‐care HCV RNA testing on entry was beneficial for care engagement. Point‐of‐care testing was perceived as timely (compared with standard pathology) and reduced opportunities for adjudication by correctional officers due to fewer clinic visits for testing and results. Adoption of routine opt‐out testing at prison intake was regarded as an important strategy for normalising HCV testing (and likely to increase pathways to treatment uptake) and fostered patient candidacy (i.e. self‐perceived eligibility to access care). Conclusion: Twenty‐four men in prison in New South Wales, Australia, who underwent opt‐out point‐of‐care HCV RNA testing on entry into prison, widely supported the programme as a means of overcoming barriers to HCV testing and treatment in the prison setting, as well as providing public health benefits through early detection of HCV infection among people entering into custody. [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]

Introduction: Globally, hepatitis B virus (HBV) is a leading cause of liver disease. People who inject drugs (PWID) are at greater risk than the general population of contracting HBV. This risk could depend on societal factors in different countries. We investigated the associations between country‐level chronic HBV prevalence in PWID with national indicators of development and prevalence of HIV and hepatitis C virus (HCV). Methods: We used global systematic review data on chronic HBV prevalence (hepatitis B surface antigen‐positive) among PWID and country‐level sociodemographic characteristics from online databases. National random‐effects meta‐analysis estimates of HBV prevalence were the outcome in linear regression models testing for associations with country‐level characteristics. Results: The study included 131,710 PWID from 304 estimates in 55 countries: the pooled HBV prevalence among PWID in the countries analysed was 4.5% (95% CI 3.9–5.1), the highest regional pooled prevalence was in East and Southeast Asia (17.6% [13.3–22.3]), and the lowest was in Western Europe (1.7% [1.4–2.1]). In multivariable models, no indicators of development were associated with HBV prevalence, but there was evidence of positive associations between HBV prevalence in the general population and among PWID, and evidence of HIV and HCV prevalence in PWID being associated with HBV prevalence in PWID: multivariable coefficients 0.03 (95% CI 0.01–0.04); p < 0.001, and 0.01 (95% CI 0.00–0.03); p = 0.01, respectively. Discussion and Conclusions: HBV prevalence among PWID was associated with HIV and HCV prevalence among PWID and background HBV prevalence in the general population, highlighting the need for improving harm reduction in PWID and implementation of HBV vaccination, especially where HBV is endemic. [ABSTRACT FROM AUTHOR]

To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV–HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care (plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03–49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07–0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7–100.0), and the specificity was 99.2% (95% CI 95.9–99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings. [ABSTRACT FROM AUTHOR]

Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment‐induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct‐acting antivirals (DAA) prevents establishment of, or reverses, T‐cell exhaustion, leading to a virus‐specific T‐cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV‐specific T‐cell responses before and after DAA or interferon‐based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme‐linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n = 17), acute interferon (n = 14), acute DAA (n = 13) and chronic DAA (n = 11). After controlling for sex, the magnitude of post‐treatment HCV‐specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV‐specific responses post‐treatment. However, individuals with spontaneous clearance had broader HCV‐specific responses. [ABSTRACT FROM AUTHOR]

Background: New technologies and therapies allow the possibility of a single-visit test and treat model for hepatitis C virus (HCV), addressing some of the barriers to care faced by people who inject drugs. Methods: The TEMPO Pilot Study was an interventional cohort study evaluating a single-visit test and treat intervention among people with recent injecting drug use at a one peer-led needle and syringe program (NSP) in Sydney, Australia between September 2019 and February 2021. This analysis evaluated awareness of HCV status and agreement of self-report with HCV RNA test results. The analysis also assessed acceptability of: modality of result delivery, modality of blood sampling, site of treatment, and duration of treatment. Results: Among 101 participants (median age 43; 31% female), 100 had a valid HCV RNA test result and 27% (27/100) were HCV RNA detectable. Overall, 65% (65/100) were aware of their status. Among people with a positive HCV RNA result, 48% (13/27) were aware of their status. People preferred same-day HCV test results (95%, 96/101), and preferred to receive results in person (69%, 70/101). Receiving treatment at an NSP was acceptable (100%, 101/101) and 78% (79/101) were willing to discuss their health with a peer NSP worker. Conclusion: Half of people with current HCV infection were aware of their status. The high acceptability of simplified testing and treatment pathways delivered at NSPs indicates that this is an appropriate strategy to improve HCV awareness and treatment uptake in this population. [ABSTRACT FROM AUTHOR]

Background: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA.Methods: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates.Results: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%).Conclusions: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs. [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]

Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had "low" microelimination scores, 11 had "high" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211. [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]

Introduction: Awareness of hepatitis C virus (HCV) status among people who inject drugs is critical to ensure linkage to care and reduce transmission risk. Testing pathways, confusion about results and possible reinfection raise potential for discordance between perceived and actual HCV status among people who inject drugs. We evaluated self‐reported and serologically confirmed HCV status concordance among a sample of Australian people who inject drugs. Methods: Data were collected in May–June 2018 from participants in Canberra and Sydney, Australia, who had injected drugs at least monthly in the past 6 months. Participants completed a structured interview assessing self‐reported HCV status and provided a dried blood spot sample for HCV RNA testing. Results: Of 103 participants, 95% self‐reported ever receiving antibody testing, 58% of whom reported having received RNA testing. Seventy‐three percent of participants reported never having been told that they had HCV, 18% reported current infection and 9% did not know their current status. According to dried blood spot RNA testing, 20% were currently infected. Over a quarter of the sample (28%, n = 29) did not accurately report their HCV status, half of whom were unaware of a current infection. Discussion and Conclusions: With over one‐quarter of the sample in our study not accurately reporting their current HCV status, our findings reinforce the importance of regular testing for active infection, and the need for improved health literacy on HCV antibody and RNA test results, HCV status post‐treatment and reinfection risk. [ABSTRACT FROM AUTHOR]

The World Health Organization 2030 targets for hepatitis C virus (HCV) elimination include diagnosing 90% of people with HCV and treating 80% of people diagnosed with HCV. This systematic review assessed reported data on the HCV care cascade in various countries and populations, with a focus on direct‐acting antiviral (DAA) treatment uptake. Bibliographic databases and conference presentations were searched for studies reporting the HCV care cascade (DAA treatment uptake was a requirement) among the overall population with HCV or sub‐populations at greater risk of HCV. Population‐based studies, with participants representative of a city, province/state or country were eligible. Twenty eligible studies were included, reporting HCV care cascade in 28 populations/sub‐populations from 11 countries. DAA treatment uptake at national levels was reported from Iceland (95%), Egypt (92%), Georgia (79%), Norway (18%) and Sweden (8%), and at sub‐national levels from the Netherlands (52%), Canada (50%), the United States (29%) and Denmark (5%). Among people with HIV‐HCV co‐infection, DAA treatment uptake was 62% in Canada, 44% in the Netherlands, 21% in Switzerland and 18% in the United States. Among people who inject drugs, DAA treatment uptake was 50% in Georgia, 40% in Canada, 37% in Australia and 13% in the United States. Data among people experiencing homelessness were only available from the United States (treatment uptake: 12%–14%). We found no eligible study reporting HCV care cascade data in prisons. Relatively few countries reported HCV care cascade at the national level. DAA treatment uptake was widely varied across populations/sub‐populations, with higher rates reported in recent years. [ABSTRACT FROM AUTHOR]

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030. [ABSTRACT FROM AUTHOR]

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.Objective: To estimate the association of time receiving OAT with mortality.Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included.Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses.Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically.Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56).Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits. [ABSTRACT FROM AUTHOR]

Background Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. Methods The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). Results Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00–2.16), incarcerated in the previous year (2.04; 1.38–3.02), and those injecting drugs daily or more (2.26; 1.43–2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68;.48–.95), participants who were homeless (.59;.38–.96), and those injecting daily or more (.51;.31–.89). People aged ≥45 years (1.46; 1.06–2.01) and people receiving OAT (2.62; 1.52–4.51) were more likely to report HCV treatment. Conclusions Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment. [ABSTRACT FROM AUTHOR]

Background: With direct-acting antivirals dramatically reshaping the public health response to the hepatitis C virus (HCV), prisons are set to play a critical role in elimination efforts. Despite the theoretical demonstration of HCV treatment-as-prevention in prison in mathematical modeling, limited empirical data exist. The Australian 'Surveillance and Treatment of Prisoners with Hepatitis C' project (SToP-C) is the world's first trial of HCV treatment-as-prevention in prison. Drawing on interviews with HCV expert stakeholders, this paper explores the factors respondents identified as crucial to the success of future scale-up. Accounting for such perspectives matters because of the influence expert discourse has in shaping implementation. Methods: Semi-structured interviews were conducted with nineteen HCV experts working across key policy, advocacy, research and clinical dimensions of the Australian HCV response. Data were coded using qualitative data management software (NVivo 11). Analysis proceeded via a hybrid deductive and inductive approach. Results: Notwithstanding concerns regarding the lack of primary prevention in Australian prisons, stakeholders reported broad levels of support for the intervention and for the future scale-up of HCV treatment. A number of considerations, both external and internal to the prison system, were identified as key. The principal external factor was an enabling political-cum-policy environment; internal factors included: obtaining support from prisons' executive and custodial staff; promoting health within a security-first institutional culture; allocating time for treatment within prisoners' tightly regulated schedules; ensuring institutional stability during treatment given the routine movement of prisoners between prisons; prioritizing the availability of retreatment given the paucity of primary prevention; and securing sufficient clinical space for treatment. Conclusion: The challenges to implementation are considerable, ranging from macrolevel concerns to in-prison logistical matters. Nonetheless, we argue that prisons remain an obvious setting for treatment scale-up, not only for prevention and potential elimination benefit, but for the treatment opportunities they afford a socially disadvantaged and underserved population. While noting widespread concerns among respondents regarding the paucity of primary prevention in Australian prisons, results indicate broad levels of support among expert stakeholders for HCV treatment scale-up in prison. [ABSTRACT FROM AUTHOR]

Background: Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations.Methods: We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard).Results: One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%-35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2 = 0.96).Conclusions: The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility. [ABSTRACT FROM AUTHOR]

The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment. [ABSTRACT FROM AUTHOR]

Background: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment.Methods: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia.Results: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (n = 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (n = 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level.Conclusions: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment. [ABSTRACT FROM AUTHOR]

Background Unrestricted access to direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has been available in Australia since March 2016. Individuals with HIV-HCV co-infection are at a greater risk of liver fibrosis progression. This study estimated DAA treatment uptake among individuals with HIV-HCV co-infection, during the first year of DAA treatment access in Australia.Methods: Pharmaceutical Benefits Scheme (PBS) data on dispensed DAA and antiretroviral therapy (ART) prescriptions from March 2016 to March 2017 were used for analysis.Results: During March 2016 to March 2017, a total of 935 individuals with HIV-HCV co-infection were receiving ART and initiated DAA treatment, with 93% to 97% completing their prescribed course. Estimated DAA treatment uptake in the HIV-HCV-infected population was 41% (935/2290). Most were men (94%). Median age was 50 years. DAA treatment was initiated by specialists in 64% of cases (n = 602), and by general practitioners (GPs) in 25% of cases (n = 238). The proportion of individuals initiated on DAA by GPs increased from 20% in March-April 2016 to 26% in January-March 2017. Most specialists (77%) and GPs (72%) initiated DAA treatment for one to three patients. Among individuals initiated on DAA by GPs, 68% received their ART prescription from the same GP.Conclusions: A high level of DAA treatment uptake and completion was observed among individuals with HIV-HCV co-infection during the first year of DAA treatment access. The proportion of individuals prescribed DAA by GPs increased over time; this is important for broadened access. [ABSTRACT FROM AUTHOR]

Background & Aims: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non‐adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non‐adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non‐adherence on sustained virological response at post‐treatment week 12 (SVR12) rates in HCV genotype (GT) 1‐6‐infected patients. Methods: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non‐adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent‐to‐treat (ITT) population and modified ITT (mITT) population, which excludes non‐virological failures. Results: Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non‐adherence to G/P therapy (OR: 2.38; 95% CI: 1.13‐5.01; P =.022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P =.047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively. Conclusions: Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment. Clinical trials registration: NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717. [ABSTRACT FROM AUTHOR]

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct‐acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole‐blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre‐DAA era to 38% in the DAA era. Significant liver fibrosis (F2‐F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18‐7.04) and attending a clinical follow‐up with nurse (aOR, 3.19; 95% CI, 1.61‐6.32) or physician (aOR, 11.83; 95% CI, 4.89‐28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake. [ABSTRACT FROM AUTHOR]

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets. [ABSTRACT FROM AUTHOR]

The global scale‐up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two‐drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6‐36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90‐100) and 100% (95% CI: 93‐100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80‐97) and 92.5% (95% CI: 82‐98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97‐100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture. [ABSTRACT FROM AUTHOR]

People who are homeless have increased hepatitis C virus (HCV) infection risk, and are less likely to access primary healthcare. We aimed to evaluate HCV RNA prevalence, liver disease burden, linkage to care and treatment uptake and outcomes among people attending a homelessness service in Sydney. Participants were enrolled in an observational cohort study with recruitment at a homelessness service over eight liver health campaign days. Finger‐stick whole‐blood samples for Xpert® HCV Viral Load and venepuncture blood samples were collected. Participants completed a self‐administered survey and received transient elastography and clinical assessment by a general practitioner or nurse. Clinical follow‐up was recommended 2‐12 weeks after enrolment. For participants initiating direct‐acting antiviral (DAA) therapy, medical records were audited retrospectively and treatment outcome data were collected. Among 202 participants (mean age, 48 years), 82% were male (n = 165), 39% (n = 78) reported ever injecting drugs, of whom 63% (n = 49) injected in the previous month. Overall, 23% (n = 47) had detectable HCV RNA and 6% (n=12) had cirrhosis. HCV RNA prevalence among participants with either injecting or incarceration history was 35% (37/105), compared to 4% (3/73) among participants without these risk factors. Among those with detectable HCV RNA, 23 (49%) commenced therapy, of whom 65% (n = 15) achieved sustained virological response, while the remainder had no available treatment outcome. No participant had documented virological failure. HCV DAA treatment uptake among people attending a homelessness service was encouraging, but innovative models of HCV care are required to improve linkage to care and treatment uptake among this highly marginalized population. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.Methods: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.Results: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.Conclusion: Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST. [ABSTRACT FROM AUTHOR]

Summary: Interactions between the host immune system and the viral variants determine persistence of hepatitis C virus (HCV) infection after the acute phase of infection. This study describes the genetic variability of within‐host HCV viral variants in acute infection and correlates it with host‐ and virus‐related traits and infection outcome. Next generation sequence data (Illumina, MiSeq platform) of viral genomes from 116 incident acute infections (within 180 days of infection) were analysed to determine all the single nucleotide polymorphism (SNP) frequencies above a threshold of 0.1%. The variability of the SNPs for the full open reading frame of the genome as well as for each protein coding region were compared using mean standardized Shannon entropy (SE) values calculated separately for synonymous and nonsynonymous mutations. The envelope glycoproteins regions (E1 and E2) had the highest SE values (indicating greater variability) followed by the NS5B region. Nonsynonymous mutations rather than synonymous mutations were the main contributors to genomic variability in acute infection. The mean difference of Shannon entropy was also compared between subjects after categorizing the samples according to host and virus‐related traits. Host IFNL3 allele CC polymorphism at rs12979860 (vs others) and viral genotype 1a (vs 3a) were associated with higher genomic variability across the viral open reading frame. Time since infection, host gender or continent of origin was not associated with the viral genomic variability. Viral genomic variability did not predict spontaneous clearance. [ABSTRACT FROM AUTHOR]

Summary: Subsidized direct‐acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32 600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016‐2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub‐populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN‐based) scenario. During 2016‐2030, we estimated an intermediate DAA treatment scenario (2016, 32 600 treated; 2017, 21 370 treated; 2018 17 100 treated; 2019 and beyond, 13 680 treated each year) would avert 40 420 new HCV infections, 13 260 liver‐related deaths (15 320 in viraemic; −2060 in cured) and 10 730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN‐based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver‐related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15 years. The pre‐DAA escalation in those with advanced liver disease makes the achievement of the liver‐related mortality target difficult. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized. [ABSTRACT FROM AUTHOR]

Background: Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia.Methods: We applied a multiplier method which used benchmark data (number of people in opioid substitution therapy (OST) on a snapshot day in 2014) and multiplied it by a factor derived from the prevalence of current OST among people who inject drugs participating in the Australian Needle and Syringe Program Survey in 2014. Estimates of the total population of people who inject drugs were calculated in each state and territory and summed to produce a national estimate. We used the sex and age group distribution seen in datasets relating to people who inject drugs to derive sex- and age-stratified estimates, and calculated prevalence per 1000 population.Results: Between 68,000 and 118,000 people aged 15-64 years inject drugs in Australia. The population prevalence of injecting drug use was 6.0 (lower and upper uncertainty intervals of 4.3 and 7.6) per 1000 people aged 15-64 years. Injecting drug use was more common among men than women, and most common among those aged 35-44 years. Comparison of expected drug-related deaths based on these estimates to actual deaths suggest that these figures may be underestimates.Conclusions: These are the first indirect prevalence estimates of injecting drug use in Australia in over a decade. This work has identified that there are limited data available to inform estimates of this population. These estimates can be used as a basis for further work estimating injecting drug use in Australia. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is endemic among people who inject drugs (PWID) globally. Despite high prevalence, treatment uptake is low, with cumulative uptake <10% in most settings. This study aimed to populate the cascade of HCV testing, care and treatment among PWID using data collected in Australia prior to the introduction of broadly accessible interferon-free direct-acting antiviral (DAA) therapies in March 2016.Methods: The Australian Needle and Syringe Program Survey is a cross-sectional surveillance system that recruits ∼2300 PWID annually and collects behavioural data and dried blood samples (DBS). HCV antibody and ribonucleic acid (RNA) test results from DBS collected in 2015 were combined with data on HCV diagnostic testing, care and treatment to populate the HCV cascade among Australian PWID.Results: Among an estimated 93,000 PWID in Australia in 2015, the majority (89%) had a lifetime history of HCV antibody testing. More than half (57%) of PWID tested HCV antibody positive and of these, 79% had detectable HCV RNA consistent with active infection. Less than half (46%) of HCV antibody positive PWID had received confirmatory HCV RNA testing. Among the estimated 43,201 PWID with active infection or chronic infection that had been successfully treated, 31% had received specialist HCV assessment, 8% had received antiviral treatment and 3% were cured.Conclusion: This study provides baseline estimates of the cascade of HCV testing, care and treatment among PWID through enhancement of a well-established surveillance mechanism. Characterisation of the HCV cascade among PWID will be crucial to evaluating and monitoring the roll out of direct-acting antiviral therapies in Australia, including assessing potential HCV treatment as prevention benefits. [ABSTRACT FROM AUTHOR]