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OBJECTIVE: Guidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of HCV testing among GBM. We aimed to examine trends in HCV testing and positivity from 2016 to 2022. METHODS: Using sentinel surveillance data, we examined the proportion of GBM with at least one test and the proportion with a positive test in each year for HCV antibody testing among GBM with no previous HCV positive test, HCV RNA testing among GBM with a positive antibody test but no previous positive RNA test (naïve RNA testing), and HCV RNA testing among people who had a previous RNA positive test and a subsequent negative test (RNA follow-up testing). Trends were examined using logistic regression from 2016 to 2019 and 2020 to 2022. RESULTS: Among GBM with HIV, from 2016 to 2019 antibody testing was stable averaging 55% tested annually. Declines were observed for both naïve HCV RNA testing (75.4%-41.4%: p<0.001) and follow-up HCV RNA testing (70.1%-44.5%: p<0.001). Test positivity declined for HCV antibody tests (2.0%-1.3%: p=0.001), HCV RNA naïve tests (75.4%-41.4%: p<0.001) and HCV RNA follow-up tests (11.3%-3.3%: p=0.001). There were minimal or no significant trends from 2020 to 2022.Among GBM prescribed PrEP, antibody testing declined from 2016 to 2019 (79.4%-69.4%: p<0.001) and was stable from 2020 to 2022. Naïve and follow-up HCV RNA testing was stable with an average of 55% and 60% tested each year, respectively. From 2016-2019, the proportion positive from HCV RNA naïve tests declined (44.1%-27.5%: p<0.046) with no significant change thereafter. Positive follow-up HCV RNA tests fluctuated with no or one new positive test among this group in most years. CONCLUSION: The proportion of GBM with positive HCV tests has declined, however a substantial proportion are not tested annually. A renewed focus on HCV testing, and treatment where required, is warr

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. METHODS: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. CONCLUSIONS: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than st

BACKGROUND: In 2021, the Australian Government Department of Health commissioned a consortium of modelling groups to generate evidence assisting the transition from a goal of no community COVID-19 transmission to 'living with COVID-19', with adverse health and social consequences limited by vaccination and other measures. Due to the extended school closures over 2020-21, maximizing face-to-face teaching was a major objective during this transition. The consortium was tasked with informing school surveillance and contact management strategies to minimize infections and support this goal. METHODS: Outcomes considered were infections and days of face-to-face teaching lost in the 45 days following an outbreak within an otherwise COVID-naïve school setting. A stochastic agent-based model of COVID-19 transmission was used to evaluate a 'test-to-stay' strategy using daily rapid antigen tests (RATs) for close contacts of a case for 7 days compared with home quarantine; and an asymptomatic surveillance strategy involving twice-weekly screening of all students and/or teachers using RATs. FINDINGS: Test-to-stay had similar effectiveness for reducing school infections as extended home quarantine, without the associated days of face-to-face teaching lost. Asymptomatic screening was beneficial in reducing both infections and days of face-to-face teaching lost and was most beneficial when community prevalence was high. INTERPRETATION: Use of RATs in school settings for surveillance and contact management can help to maximize face-to-face teaching and minimize outbreaks. This evidence supported the implementation of surveillance testing in schools in several Australian jurisdictions from January 2022.

The Pacific Island country of Vanuatu is considering strategies to remove border restrictions implemented during 2020 to prevent imported coronavirus disease. We performed mathematical modeling to estimate the number of infectious travelers who had different entry scenarios and testing strategies. Travel bubbles and testing on entry have the greatest importation risk reduction.

BACKGROUND: Hepatitis C elimination may be possible with broad uptake of direct-acting antiviral treatments (DAAs). In 2016 the Australian government committed A$1.2 billion for five years of unlimited DAAs (March 2016 to February 2021) in a risk-sharing agreement with pharmaceutical companies. We assess the impact, cost-effectiveness and net economic benefits likely to be realised from this investment. METHODS: Mathematical modelling to project outcomes for 2016-2030 included: (S1) a counter-factual scenario (testing/treatment maintained at pre-2016 levels); (S2) the current status-quo (testing/treatment as actually occurred 2016-2019, with trends maintained to 2030); and (S3) elimination scenario (S2 plus testing/treatment rates increased between 2021-2030 to achieve the WHO elimination targets). FINDINGS: S1 resulted in 68,800 new hepatitis C infections and 18,540 hepatitis C-related deaths over 2016-2030. The total health system cost (HCV testing, treatment, disease management) was A$3.01 billion and the cost of lost productivity due to absenteeism, presenteeism and premature deaths was A$26.14 billion. S2 averted 15,700 (23%) new infections and 8,500 (46%) deaths by 2030, with a total health system cost of A$3.48 billion, A$472 million more than S1 (A$1.65 billion more in testing/treatment but A$1.20 billion less in disease costs; A$5,752 per QALY gained from a health systems perspective). Productivity loss over 2016-2030 was A$19.96 billion, A$6.17 less than S1, making S2 cost-saving from a societal perspective by 2022 with a net economic benefit of A$5.70 billion by 2030. S3 averted an additional 10,000 infections and 930 deaths compared with S2 and increased the longer-term economic benefit. INTERPRETATION: Five years of unrestricted access to DAAs in Australia has led to significant health benefits and is likely to become cost-saving from a societal perspective by 2022. FUNDING: Burnet Institute.

BACKGROUND: Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS: People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS: Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION: A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

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

BACKGROUND: In settings with zero community transmission, any new SARS-CoV-2 outbreaks are likely to be the result of random incursions. The level of restrictions in place at the time of the incursion is likely to considerably affect possible outbreak trajectories, but the probability that a large outbreak eventuates is not known. METHODS: We used an agent-based model to investigate the relationship between ongoing restrictions and behavioural factors, and the probability of an incursion causing an outbreak and the resulting growth rate. We applied our model to the state of Victoria, Australia, which has reached zero community transmission as of November 2020. RESULTS: We found that a future incursion has a 45% probability of causing an outbreak (defined as a 7-day average of > 5 new cases per day within 60 days) if no restrictions were in place, decreasing to 23% with a mandatory masks policy, density restrictions on venues such as restaurants, and if employees worked from home where possible. A drop in community symptomatic testing rates was associated with up to a 10-percentage point increase in outbreak probability, highlighting the importance of maintaining high testing rates as part of a suppression strategy. CONCLUSIONS: Because the chance of an incursion occurring is closely related to border controls, outbreak risk management strategies require an integrated approaching spanning border controls, ongoing restrictions, and plans for response. Each individual restriction or control strategy reduces the risk of an outbreak. They can be traded off against each other, but if too many are removed there is a danger of accumulating an unsafe level of risk. The outbreak probabilities estimated in this study are of particular relevance in assessing the downstream risks associated with increased international travel.

OBJECTIVES: To assess the risks associated with relaxing coronavirus disease 2019 (COVID-19)-related physical distancing restrictions and lockdown policies during a period of low viral transmission. DESIGN: Network-based viral transmission risks in households, schools, workplaces, and a variety of community spaces and activities were simulated in an agent-based model, Covasim. SETTING: The model was calibrated for a baseline scenario reflecting the epidemiological and policy environment in Victoria during March-May 2020, a period of low community viral transmission. INTERVENTION: Policy changes for easing COVID-19-related restrictions from May 2020 were simulated in the context of interventions that included testing, contact tracing (including with a smartphone app), and quarantine. MAIN OUTCOME MEASURE: Increase in detected COVID-19 cases following relaxation of restrictions. RESULTS: Policy changes that facilitate contact of individuals with large numbers of unknown people (eg, opening bars, increased public transport use) were associated with the greatest risk of COVID-19 case numbers increasing; changes leading to smaller, structured gatherings with known contacts (eg, small social gatherings, opening schools) were associated with lower risks. In our model, the rise in case numbers following some policy changes was notable only two months after their implementation. CONCLUSIONS: Removing several COVID-19-related restrictions within a short period of time should be undertaken with care, as the consequences may not be apparent for more than two months. Our findings support continuation of work from home policies (to reduce public transport use) and strategies that mitigate the risk associated with re-opening of social venues.

BACKGROUND AND AIM: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years. METHODS: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015. RESULTS: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015. CONCLUSIONS: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.

An increasing number of countries are committing to meet the World Health Organization (WHO) targets to eliminate hepatitis C virus (HCV) as a public health threat by 2030. These include service coverage targets (90% diagnosed and 80% of diagnosed patients treated) and impact targets (80% and 65% reductions in incidence and mortality, respectively, compared to 2015 levels). Currently, a dozen countries are on track to reach 2030 WHO HCV targets. However, while striving for the WHO targets is important, it should be recognized that progress on impact targets is derived from mathematical models projecting decreases in incidence and mortality on a global scale. Despite HCV treatment access in many counties for a number of years, limited empirical data are available to evaluate progress towards elimination. In some countries, substantial incidence and mortality reductions based on reaching the WHO service coverage targets may be unachievable. For example, in countries with ageing hepatitis C-infected populations, even if they have a quality hepatitis C response, high hepatitis C-related morbidity at baseline may not be reversible even with increased HCV treatment uptake and diagnosis. Finally, WHO targets are not necessarily easily or reliably measurable. Measuring relative impact targets requires high-quality data at baseline (ie 2015) and longitudinal data to assess temporal trends. In this commentary, we propose alternative additional measures to track progress on reducing the HCV burden, offer examples where the WHO targets may not be informative or achievable, and potential practical solutions.

OBJECTIVES: To assess progress in Australia toward the 2030 WHO hepatitis C elimination targets two years after the introduction of highly effective direct-acting antiviral (DAA) treatments. DESIGN: Analysis of quarterly data on government-subsidised hepatitis C RNA testing and hepatitis C treatment in Australia, January 2013 - June 2018. Changes in testing and treatment levels associated with DAA availability were assessed in an autoregressive integrated moving average (ARIMA) statistical model, and the impact by 2030 of different levels of testing and treatment were estimated using a mathematical model. MAJOR OUTCOME MEASURES: Hepatitis C prevalence among people who inject drugs; annual hepatitis C incidence relative to 2015 levels; projections for the hepatitis C care cascade in 2030. RESULTS: The mean annual number of treatments initiated for people with hepatitis C increased from 6747 during 2013-2015 (before the introduction of DAAs) to 28 022 during 2016-18; the mean annual number of diagnostic RNA tests increased from 17 385 to 23 819. If current trends in testing and treatment continue (ie, 2018 testing numbers are maintained but treatment numbers decline by 50%), it is projected that by 2030 only 72% of infected people would be treated (by 2025 all people diagnosed with hepatitis C would be treated). The incidence of hepatitis C in 2030 would be 59% lower than in 2015, well short of the WHO target of an 80% reduction. The identification and testing of people exposed to hepatitis C must be increased by at least 50% for Australia to reach the WHO elimination targets. CONCLUSION: Hepatitis C elimination programs in Australia should focus on increasing testing rates and linkage with care to maintain adequate levels of treatment.

BACKGROUND: It is estimated that approximately half of new HIV diagnoses among heterosexual migrants in Victoria, Australia, were acquired post-migration. We investigated the characteristics of phylogenetic clusters in notified cases of HIV among heterosexual migrants. METHODS: Partial HIV pol sequences obtained from routine clinical genotype tests were linked to Victorian HIV notifications with the following exposures listed on the notification form: heterosexual sexual contact, injecting drug use, bisexual sexual contact, male-to male sexual contact or heterosexual sexual contact in combination with injecting drug use, unknown exposure. Those with heterosexual sexual contact as the only exposure were the focus of this study, with the other exposures included to better understand transmission networks. Additional reference sequences were extracted from the Los Alamos database. Maximum likelihood methods were used to infer the phylogeny and the robustness of the resulting tree was assessed using bootstrap analysis. Phylogenetic clusters were defined on the basis of bootstrap and genetic distance. RESULTS: HIV pol sequences were available for 332 of 445 HIV notifications attributed to only heterosexual sexual contact in Victoria from 2005-2014. Forty-three phylogenetic clusters containing at least one heterosexual migrant were detected, 30 (70%) of which were pairs. The characteristics of these phylogenetic clusters varied considerably by cluster size. Pairs were more likely to be composed of people living with HIV from a single country of birth (p = 0.032). Larger clusters (n≥3) were more likely to contain people born in Australian/New Zealand (p = 0.002), migrants from more than one country of birth (p = 0.013) and viral subtype-B, the most common subtype in Australia (p = 0.006). Pairs were significantly more likely to contain females (p = 0.037) and less likely to include HIV diagnoses with male-to-male sexual contact reported as a possible exposure (p<0.001) com

BACKGROUND: Global targets to eliminate hepatitis C (HCV) might be met by sustained treatment uptake. AIM: To describe factors facilitating HCV treatment uptake and potential challenges to sustaining treatment levels after universal access to direct-acting anti-virals (DAA) across Australia. METHODS: We analysed national Pharmaceutical Benefits Scheme data to determine the number of DAA prescriptions commenced before and after universal access from March 2016 to June 2017. We inferred facilitators and barriers to treatment uptake, and challenges that will prevent local and global jurisdictions reaching elimination targets. RESULTS: In 2016, 32 877 individuals (14% of people living with HCV in Australia) commenced HCV DAA treatment, and 34 952 (15%) individuals commenced treatment in the first year of universal access. Treatment uptake peaked at 13 109 DAA commencements per quarter immediately after universal access, but more than halved (to 5320 in 2017 Q2) within 12 months. General practitioners have written 24% of all prescriptions but with a significantly increased proportion over time (9% in 2016 Q1 to 37% in 2017 Q2). In contrast, hepatology or infectious diseases specialists have written a declining share from 74% to 38% during the same period. General practitioners provided a greater proportion (47%) of care in regional/remote areas than major cities. CONCLUSIONS: Broad treatment access led to rapid initial increases in treatment uptake, but this uptake has not been sustained. Our results suggest achieving global elimination targets requires more than treatment availability: people with HCV need easy access to testing and linkage to care in community settings employing a diverse prescriber base.

Social network characteristics of people who inject drugs (PWID) have previously been flagged as potential risk factors for HCV transmission such as increased injection frequency. To understand the role of the injecting network on injection frequency, we investigated how changes in an injecting network over time can modulate injecting risk behaviour. PWID were sourced from the Networks 2 Study, a longitudinal cohort study of PWID recruited from illicit drug street markets across Melbourne, Australia. Network-related correlates of injection frequency and the change in frequency over time were analysed using adjusted Cox Proportional Hazards and Generalised Estimating Equations modelling. Two-hundred and eighteen PWID followed up for a mean (s.d.) of 2.8 (1.7) years were included in the analysis. A greater number of injecting partners, network closeness centrality and eigenvector centrality over time were associated with an increased rate of infection frequency. Every additional injection drug partner was associated with an increase in monthly injection frequency. Similarly, increased network connectivity and centrality over time was also associated with an increase in injection frequency. This study observed that baseline network measures of connectivity and centrality may be associated with changes in injection frequency and, by extension, may predict subsequent HCV transmission risk. Longitudinal changes in network position were observed to correlate with changes in injection frequency, with PWID who migrate from the densely-connected network centre out to the less-connected periphery were associated with a decreased rate of injection frequency.

Background: People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings: We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21%

Introduction: Students comprised the majority of early cases of influenza A(H1N1)pdm09 in Melbourne, Australia. Students and school settings were targeted for public health interventions following the emergence of pH1N1. This study was conducted to describe changes in social contacts among the earliest confirmed student cases of pH1N1 in Melbourne, Australia, to inform future pandemic control policy and explore transmission model assumptions. Methods: A retrospective cross-sectional behavioural study of student cases with laboratory-confirmed pH1N1 between 28 April and 3 June 2009 was conducted in 2009. Demographics, symptom onset dates and detailed information on regular and additional extracurricular activities were collected. Summary measures for activities were calculated, including median group size and median number of close contacts and attendance during the students’ exposure and infectious periods or during school closures. A multivariable model was used to assess associations between rates of participation in extracurricular activities and both school closures and students’ infectious periods. Results: Among 162 eligible cases, 99 students participated. Students reported social contact in both curricular and extra-curricular activities. Group size and total number of close contacts varied. While participation in activities decreased during the students’ infectious periods and during school closures, social contact was common during periods when isolation was advised and during school closures. Discussion: This study demonstrates the potential central role of young people in pandemic disease transmission given the level of non-adherence to prevention and control measures. These finding have public health implications for both informing modelling estimates of future pandemics and targeting prevention and control strategies to young people.

INTRODUCTION: There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. METHODS: HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. RESULTS: Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). CONCLUSIONS: Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase di

Modelling suggests that more frequent screening of people who inject drugs (PWID) and an improved care cascade are required to achieve the WHO hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030. We determined the testing frequencies (2-yearly, annually, 6-monthly and 3-monthly) and retention in care required among PWID to achieve the HCV incidence reduction target through treatment as prevention in low (25%), medium (50%) and high (75%) chronic HCV prevalence settings. Mathematical modelling of HCV transmission among PWID, capturing testing, treatment and other features of the care cascade were employed. In low-prevalence settings, 2-yearly antibody testing of PWID was estimated to reach the elimination target by 2027-2030 depending on retention in care, with annual testing reducing the time by up to 3 years. In medium-prevalence settings, if close to 90% testing coverage were achieved, then annual antibody testing of PWID would be sufficient. If testing coverage were lower (80%), 6-monthly antibody testing with at least 70% retention in care or annual HCV RNA/cAg testing would be required. In high-prevalence settings, even 3-monthly HCV RNA/cAg testing of PWID was unable to achieve the incidence reduction target. Thus, for geographical areas or subpopulations with high prevalence, WHO incidence targets are unlikely to be met without 3-monthly RNA/cAg testing accompanied by other prevention measures. Novel testing strategies, such as rapid point-of-care antibody testing or replacing antibody testing with RNA/cAg tests as a screening tool, can provide additional population-level impacts to compensate for imperfect follow-up or testing coverage.

Background This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM). Methods This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering. Results Forty individuals were recruited, of whom 62.5%were considered to have sexually-and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions. Conclusions Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission.

BACKGROUND: This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM). METHODS: This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering. RESULTS: Forty individuals were recruited, of whom 62.5% were considered to have sexually- and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions. CONCLUSIONS: Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission.

BACKGROUND AND AIMS: Prescription opioid injection (POI) is a leading risk factor for hepatitis C virus (HCV). Residential context relates to high‐risk injection behaviour. This study assessed whether residence in the inner city (versus surrounding areas in Montréal Island) modified the effects of correlates of POI or the relationship between POI and HCV incidence. DESIGN: Prospective cohort study. SETTING: Montréal, Canada. PARTICIPANTS: A total of 854 people who inject drugs (18% female, 25% age < 30 years), living on Montréal Island, were interviewed every 3–6 months from 2004 to 2012. MEASUREMENTS: Study visits included HCV antibody testing and an interviewer‐administered questionnaire. Generalized estimating equations were used to test whether place of residence modified the effects of correlates of POI. Cox regression was used to test whether place of residence modified the relationship between POI and HCV incidence. FINDINGS: At baseline, inner‐city participants were more likely to report POI in the past month (40 versus 25%, P < 0.001). The association between POI and heroin injection, syringe sharing and sharing of injecting equipment varied according to place of residence and was greater in the inner city. The hazard of HCV infection associated with POI was greater among inner‐city participants compared to those in the surrounding areas [adjusted hazard ratio (HR) = 3.38, 95% confidence interval (CI) = 1.88–6.07 versus HR = 1.26, 95% CI = 0.65–2.42, P = 0.025]. CONCLUSIONS: Among people who inject prescription opioids in Montréal, Canada, those who live in inner‐city areas are more likely to engage in injecting‐related risk behaviours and have a higher risk of hepatitis C virus infection than those who live in the suburbs.

Summary Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC3 study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.

Background.We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance. Methods.Data were synthesized from the 9 prospective cohorts of the International Collaboration of Incident Human Immunodeficiency Virus and HCV in Injecting Cohorts study, which evaluated HCV infection outcomes among people who inject drugs. Participants with primary HCV infection were classified as having achieved viral suppression if they had negative results of at least 1 subsequent HCV RNA test. Those with positive results of an HCV RNA test following viral suppression were investigated for reinfection. Viral sequence analysis was used to identify reinfection (defined as detection of heterologous virus with no subsequent detection of the original viral strain). Results.Among 591 participants with acute primary HCV infection, 118 were investigated for reinfection. Twenty-eight participants were reinfected (12.3 cases/100 person-years; 95% confidence interval [CI], 8.5-17.8). Peak HCV RNA level was lower during reinfection than primary infection (P =. 011). The proportion of individuals with reclearance 6 months after reinfection was 52% (95% CI, 33%-73%). After adjustment for study site, females with the IFNL4 (formerly IFNL3 and IL28B) rs12979860 CC genotype detected were more likely to have reclearance (hazard ratio, 4.16; 95% CI, 1.24-13.94; P =. 021). Conclusions.Sex and IFNL4 genotype are associated with spontaneous clearance after reinfection.

Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels-≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3 ) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is a

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

Hepatitis C virus (HCV) reinfection rates are probably underestimated due to reinfection episodes occurring between study visits. A Markov model of HCV reinfection and spontaneous clearance was fitted to empirical data. Bayesian post-estimation was used to project reinfection rates, reinfection spontaneous clearance probability and duration of reinfection. Uniform prior probability distributionswere assumed for reinfection rate (more than 0), spontaneous clearance probability (0-1) and duration (0.25-6.00 months). Model estimates were 104 per 100 person-years (95% CrI: 21-344), 0.84 (95% CrI: 0.59-0.98) and 1.3 months (95% CrI: 0.3-4.1) for reinfection rate, spontaneous clearance probability and duration, respectively. Simulation studies were used to assess model validity, demonstrating that the Bayesian model estimates provided useful information about the possible sources and magnitude of bias in epidemiological estimates of reinfection rates, probability of reinfection clearance and duration or reinfection. The quality of the Bayesian estimates improved for larger samples and shorter test intervals. Uncertainty in model estimates notwithstanding, findings suggest that HCV reinfections frequently and quickly result in spontaneous clearance, with many reinfection events going unobserved.

Background Hepatitis C virus (HCV) testing and counselling have the potential to impact individual behaviour and transmission dynamics at the population level. Evidence of the impact of an HCV-positive status notification on injection risk reduction is limited. The objective of our study was to (1) assess drug and alcohol use and injection risk behaviours following notification; (2) to compare behaviour change in people who inject drugs (PWID) who received a positive test result and those who remained negative; and (3) to assess the effect of age on risk behaviour. Methods Data from the International Collaboration of Incident HIV and HCV Infection in Injecting Cohorts (InC3 Study) were analysed. Participants who were initially HCV seronegative were followed prospectively with periodic HCV blood testing and post-test disclosure and interview-administered questionnaires assessing drug use and injection behaviours. Multivariable generalised estimating equations were used to assess behavioural changes over time. Results Notification of an HCV-positive test was independently associated with a small increase in alcohol use relative to notification of a negative test. No significant differences in postnotification injection drug use, receptive sharing of ancillary injecting equipment and syringe borrowing postnotification were observed between diagnosis groups. Younger PWID receiving a positive HCV test notification demonstrated a significant increase in subsequent alcohol use compared with younger HCV negative. Conclusions The proportion of PWID reporting alcohol use increased among those receiving an HCV-positive notification, increased the frequency of alcohol use postnotification, while no reduction in injection drug use behaviours was observed between notification groups. These findings underscore the need to develop novel communication strategies during post-test notification to improve their impact on subsequent alcohol use and risk behaviours.

BACKGROUND: Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. METHODS: Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. RESULTS: Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). CONCLUSIONS: Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female s

BACKGROUND: Online social networking platforms such as Facebook and Twitter have grown rapidly in popularity, with opportunities for interaction enhancing their health promotion potential. Such platforms are being used for sexual health promotion but with varying success in reaching and engaging users. We aimed to identify Facebook and Twitter profiles that were able to engage large numbers of users, and to identify strategies used to successfully attract and engage users in sexual health promotion on these platforms. METHODS: We identified active Facebook (n = 60) and Twitter (n = 40) profiles undertaking sexual health promotion through a previous systematic review, and assessed profile activity over a one-month period. Quantitative measures of numbers of friends and followers (reach) and social media interactions were assessed, and composite scores used to give profiles an 'engagement success' ranking. Associations between host activity, reach and interaction metrics were explored. Content of the top ten ranked Facebook and Twitter profiles was analysed using a thematic framework and compared with five poorly performing profiles to identify strategies for successful user engagement. RESULTS: Profiles that were able to successfully engage large numbers of users were more active and had higher levels of interaction per user than lower-ranked profiles. Strategies used by the top ten ranked profiles included: making regular posts/tweets (median 46 posts or 124 tweets/month for top-ranked profiles versus six posts or six tweets for poorly-performing profiles); individualised interaction with users (85% of top-ranked profiles versus 0% for poorly-performing profiles); and encouraging interaction and conversation by posing questions (100% versus 40%). Uploading multimedia material (80% versus 30%) and highlighting celebrity involvement (70% versus 10%) were also key strategies. CONCLUSION: Successful online engagement on social networking platforms can be measured throug

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