"You need a designated officer" - Recommendations from correctional and justice health personnel for scaling up hepatitis C treatment-as-prevention in the prison setting.

INTRODUCTION: Hepatitis C (HCV) is highly prevalent among people who are incarcerated. HCV treatment-as-prevention was implemented in the SToP-C trial in four correctional centres in New South Wales , Australia to determine whether prison-wide scale up of antiviral treatment was an effective strategy to reduce HCV incidence and prevalence in the prison setting. A qualitative assessment was undertaken with prison-based correctional and health personnel at each of the four prisons to understand operational, sociological, and cultural barriers and enablers to scale up. Informed by a framework for scaling up population health interventions, this analysis examines recommendations by correctional and justice health personnel for HCV treatment-as-prevention scale up in the prison setting. METHODS: Correctional (n=24) and justice health (n=17) personnel, including officers, nurses, and senior administrators, participated in interviews across the four prisons where SToP-C was delivered and included two maximum security, one minimum security, and one women's medium/minimum security prisons. RESULTS: Scaling up HCV treatment-as-prevention was contingent on compatibility (including sentence length), efficacy (securely funded positions for dedicated personnel and continuity of care for patients transferring between prisons), stakeholder analysis (generally the whole of prison workforce, particularly custodial officers and senior administrators), reach (reliant on peer and officer champions), and legitimised change (via dedicated officers who could instigate cultural shifts). CONCLUSION: Achieving scale up of such an intervention should be guided by an understanding of the potential barriers and enablers. This analysis showed key considerations for HCV treatment-as-prevention scale up in correctional centres.

Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Hepatitis C treatment as prevention in the prison setting: Assessments of acceptability of treatment scale up efforts by prison correctional and health personnel.

BACKGROUND: Hepatitis C (HCV) infection is prevalent in the prison setting, with sharing of unsterile injecting equipment the most common mode of transmission in high income countries. Mathematical modelling suggests that HCV treatment scale-up could prevent onward transmission, known as treatment as prevention. Direct-acting antivirals have enabled rapid scale up of HCV treatment, underpinning the first clinical trial of treatment as prevention in the prison setting. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study was carried out in four correctional centres in New South Wales, Australia. This paper utilises Sekhon's Theoretical Framework of Acceptability to examine correctional, prison health, and study personnel's assessments of acceptability of HCV treatment as prevention in the prison setting. METHODS: Correctional (n=24) and health personnel (n=17) including officers, nurses (including seven study nurses), and senior administrators across the four prisons where SToP-C was delivered, participated in interviews. This included two maximum security, one minimum security, and one women's medium/minimum security prison. Data analysis was informed by a seven-component theory of acceptability. RESULTS: Participants reported broad acceptability of HCV treatment as prevention in the prison setting across five components of acceptability (affective attitude, burden, ethicality, perceived effectiveness, and self-efficacy). Attributes contributing to acceptability included reduced HCV prevalence within the prison, and public health benefits for the community when people are released without HCV (affective attitude). Elements which may negatively impact on acceptability included limited clinic space (burden) and lack of correctional officers' understanding of availability of equivalent healthcare in the community (ethicality). System-wide prison participation was viewed as necessary for treatment as prevention to be successful (perceived effectiveness), while nonjudgmental care was seen as instrumental to HCV treatment scale up efforts (self-efficacy). CONCLUSION: Correctional and prison-based health personnel view HCV treatment as prevention as an acceptable health intervention. Overall, environmental issues relating to implementation (i.e., clinic space) were viewed as requiring a strategic approach to support prison-wide HCV treatment scale up.

Barriers and facilitators to engaging in hepatitis C management and DAA therapy among general practitioners and drug and alcohol specialists-The practitioner experience.

BACKGROUND: Since the advent of interferon-free, direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection, prescriber restrictions have been removed worldwide, permitting HCV management outside of hospital-based clinics. To date, there is limited knowledge of the practitioner experience with DAA treatments, particularly among those new to HCV care. The aim of this qualitative study was to investigate barriers and facilitators for HCV management among general practitioners (GPs) who prescribe opioid agonist therapy (OAT) and drug and alcohol specialists. METHODS: In-depth, semi-structured telephone interviews were conducted between September 2018 and April 2019. Practitioners from across Australia were purposively sampled and questioned on barriers and facilitators to HCV management in their clinic(s). Data were coded and analysed with iterative categorisation and thematical analysis. RESULTS: Thirty practitioners were interviewed. Participants expressed professional fulfillment in managing HCV care and many benefited from specialist mentorship. Most participants expressed frustration with ongoing implementation barriers, notably, a lack of onsite phlebotomy services and liver disease staging equipment. Poor venous access among persons who inject drugs was elucidated as a major barrier to treatment initiation. Some participants did not receive clinic manager support to engage in HCV care. CONCLUSION: To achieve HCV targets set by WHO by 2030, practitioners require additional implementation support. As HCV testing remains a barrier to linkage to care, practitioners should be kept well-informed of diagnostic developments. Findings also underscore the importance of initial specialist mentorship with further evidence needed for practitioners based in rural regions.

Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection.

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population.

Uptake of direct-acting antiviral treatment for chronic hepatitis C in Australia.

A government-funded interferon-free direct-acting antiviral (DAA) treatment programme for chronic hepatitis C virus (HCV) infection has been available in Australia since March 2016. This study assessed the levels and patterns of DAA treatment uptake during March-December 2016 in Australia and described the key features in the development of the programme. All prescriptions in Australia are submitted to the Pharmaceutical Benefits Scheme by dispensing pharmacies. Data on dispensed DAA prescriptions for a longitudinal cohort of individuals, representing a 10% random sample of the Pharmaceutical Benefits Scheme database, were used for estimating DAA treatment uptake and subgroup analyses. The estimated number of 32 400 individuals initiated DAA treatment in 2016, equating to 14% of people with chronic HCV infection in Australia. Most commonly prescribed DAA regimens included sofosbuvir/ledipasvir (56%, n = 18 020), sofosbuvir + daclatasvir (39%, n = 12 600) and sofosbuvir + other agents (4%, n = 1220). Among individuals initiated DAA treatment, 66% (n = 21 430) were men, 43% (n = 13 870) were ≤50 years old and 36% (n = 11 670) had cirrhosis. DAA prescriptions were 62% (n = 20 080) by specialists, 19% (n = 6000) by general practitioners (GP) and 20% (n = 6320) by other physicians. Proportion of individuals prescribed DAA by GPs increased from 8% to 31% and proportion of individuals ≤50 years old increased from 28% to 61% between March and December. In conclusion, rapid treatment scale-up was observed in the first 10 months of unrestricted DAA programme in Australia. The proportion of prescriptions by GPs increased over time, important for broadened access. A trend towards younger age treatment suggested the broadening of DAA-treated population, potentially including individuals at higher risk of HCV transmission.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Estimating HCV disease burden-volume 4 (editorial).

Hepatitis C virus (HCV) is a major global public health issue, with an estimated 71 million people living with HCV infection and a rising burden of cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. The advent of interferon-free, direct acting antiviral-based (DAA) therapies, with short duration (8-12 weeks), high efficacy, excellent tolerability and ease of delivery (once daily oral dosing), is one of the major advances in clinical medicine in recent decades, and provides the opportunity to address this growing global HCV burden. In May 2014, January 2015 and December 2015, three supplements were published in the Journal of Viral Hepatitis presenting data from 47 countries on the historical epidemiology of HCV, the current HCV-related morbidity and mortality and potential strategies to manage the HCV disease burden in the future. The countries included in those manuscripts were from multiple regions including North and South America, Europe, Asia, the Middle East, Africa and Oceania. In this supplement, data from an additional 17 countries are presented, following a similar pattern as in the previous manuscripts. These countries represent a mixture of high-, middle- and low-income countries that hail from five geographical regions: Africa, Asia, Europe, Middle East and South America. Expert advisory panels were convened in each country to identify the best data sources to use and to review the assumptions and outputs from the model. In the countries considered in the current analyses, there is a wide variance in the availability of robust data.

Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005-2014: The HITS-p study.

Hepatitis C virus (HCV) transmission is high in prisons. This study investigated trends in HCV incidence and associated factors among a cohort of prisoners with a history of injecting drug use in New South Wales, Australia. Data were available from the Hepatitis C Incidence and Transmission Study-prisons (HITS-p) from 2005 to 2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion among people with ongoing injecting was assessed using Cox proportional hazards. Among 320 antibody-negative participants with a history of injecting drug use (mean age 26; 72% male), 62% (n=197) reported injecting drug use during follow-up. Overall, 93 infections were observed. HCV incidence was 11.4/100 person-years in the overall population and 6.3/100 person-years among the continually imprisoned population. A stable trend in HCV incidence was observed. Among the overall population with ongoing injecting during follow-up, ≥weekly injecting drug use frequency was independently associated with time to HCV seroconversion. Among continuously imprisoned injectors with ongoing injecting during follow-up, needle/syringe sharing was independently associated with time to HCV seroconversion. This study demonstrates that prison is a high-risk environment for acquisition of HCV infection. Needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. These findings highlight the need for the evaluation of improved HCV prevention strategies in prison, including needle/syringe programmes and HCV treatment.

Phylogenetic analysis of full-length, early infection, hepatitis C virus genomes among people with intravenous drug use: the InC3 Study.

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3 ). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities.

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up.

HCV reinfection incidence among individuals treated for recent infection.

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations.

Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife Study.

BACKGROUND: The aim of this study was to assess factors associated with baseline knowledge of HCV and liver disease, acceptability of transient elastography (TE) assessment (FibroScan(®)), and willingness and intent to receive HCV treatment among persons with a history of injection drug use participating in a liver health promotion campaign. METHODS: The LiveRLife campaign involved three phases: (1) campaign resource development; (2) campaign resource testing; and (3) campaign implementation. Participants were enrolled in an observational cohort study with recruitment at four clinics - one primary health care facility, two OST clinics, and one medically supervised injecting centre - in Australia between May and October 2014. Participants received educational material, nurse clinical assessment, TE assessment, dried blood spot testing, and completed a knowledge survey. RESULTS: Of 253 participants (mean age 43 years), 68% were male, 71% had injected in the past month, and 75% self-reported as HCV positive. Median knowledge score was 16/23. In adjusted analysis, less than daily injection (AOR 5.01; 95% CI, 2.64-9.51) and no daily injection in the past month (AOR 3.54; 95% CI, 1.80-6.94) were associated with high knowledge (≥16). TE was the most preferred method both pre- (66%) and post-TE (89%) compared to liver biopsy and blood sample. Eighty-eight percent were 'definitely willing' or 'somewhat willing' to receive HCV treatment, and 56% intended to start treatment in the next 12 months. Approximately 68% had no/mild fibrosis (F0/F1, ≥2.5 to ≤7.4kPa), 13% moderate fibrosis (F2, ≥7.5 to ≤9.4kPa), 10% severe fibrosis (F3, ≥9.5 to ≤12.4kPa), and 9% had cirrhosis (F4, ≥12.5kPa). CONCLUSION: Liver disease and HCV knowledge was moderate. High acceptability of TE by PWID provides strong evidence for the inclusion of TE in HCV-related care, and could help to prioritise HCV treatment for those at greatest risk of liver disease progression.

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

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.

Effect of treatment willingness on specialist assessment and treatment uptake for hepatitis C virus infection among people who use drugs: the ETHOS study.

Among people who inject drugs (PWID) with chronic HCV, the association between HCV treatment willingness and intent, and HCV specialist assessment and treatment were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort. Recruitment was through six opioid substitution treatment clinics, two community health centres and one Aboriginal community controlled health organisation in Australia. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 67% were 'definitely willing' to receive HCV treatment and 70% reported plans to initiate therapy 12 months postenrolment. Those definitely willing to receive HCV treatment were more likely to undergo specialist assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001), compared to those with lower treatment willingness. Those with early HCV treatment plans were more likely to undergo specialist assessment (65% vs 27%, P < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without early plans. In adjusted analyses, HCV treatment willingness independently predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI 2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment willingness was high and predicted specialist assessment and treatment. Strategies for enhanced HCV care should be developed with an initial focus on people willing to receive treatment and to increase treatment willingness among those less willing.

A longitudinal study of hepatitis C virus testing and infection status notification on behaviour change in people who inject drugs.

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.

Estimates on HCV disease burden worldwide - filling the gaps.

Hepatitis C is caused by infection with the hepatitis C virus (HCV) and represents a major global health burden. Persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma, possibly accounting for up to 0.5 million deaths every year. Treatment of HCV infection is undergoing a profound and radical change. As new treatments are extremely safe and effective, there are virtually no medical reasons to withhold therapy. Yet, the new therapies are expensive. As resources are limited, solid data to estimate the disease burden caused by HCV are urgently needed. Epidemiology data and disease burden analyses for 16 countries are presented. For almost all countries, the peak of HCV-related cirrhosis, hepatocellular carcinoma and liver-related death is a decade or more away. However, a surprising heterogeneity in country-specific HCV-associated disease burden exists. Also, HCV diagnosis and treatment uptake varied markedly between countries. A consistent finding was that a reduction of HCV liver-related mortality is dependent on access to therapy. Increasing efficacy of therapy alone with a constant numbers of treatments will not have a major impact on the HCV-related disease burden. The data presented here should inform public health policy and help drive advocacy for enhanced strategic investment and action. HCV kills patients, and the disease burden will continue to rise in most countries unless action is taken soon. Chronic HCV is a curable infection and a reversible liver disease. Fortunately, the tools to eliminate HCV are now available.

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

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 (InC(3) 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.