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Background & Aims: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking., Methods: REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early., Results: The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p = 0.025)., Conclusions: In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy., Lay Summary: In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS., Gov Identifier: NCT02625909., Competing Interests: Conflict of interest GVM: grants from Gilead Sciences and AbbVie Inc, outside the submitted work; SB: grants from Gilead Sciences, outside the submitted work; personal fees for Advisory Boards and lectures/presentations from Gilead Sciences, outside the submitted work; MvDW: grants and personal fees from AbbVie, grants and personal fees from Gilead, grants and personal fees from Johnson & Johnson, grants and personal fees from MSD, grants and personal fees from ViiV, outside the submitted work; JR: personal fees from Gilead Sciences, Janssen, Merck, Theratechnologies and ViiV, outside the submitted work; JF: grants and personal fees from Gilead Sciences, grants and personal fees from AbbVie, personal fees from GSK, personal fees from Roche, grants from Janssen, grants from Eiger, grants and personal fees from Enanta, personal fees from Arubutus, outside the submitted work; AR: Advisory boards: MSD, Gilead Sciences, Travel grants: Gilead Sciences, Pfizer, AbbVie; Research support: Investigator initiated trial grant from Gilead Sciences. All remuneration went to his home institution and not to Dr. Rauch personally; CT: Gilead Advisory board (Remdesivir) 2020; MSD Advisory board (HCV) 2018; educational grants from Gilead and AbbVie (Annual Preceptorship on HCV in PWID), outside the submitted work; JB: grants from NIH, during the conduct of the study; personal fees from AbbVie, grants and personal fees from Gilead, outside the submitted work; AK: grants from PCORI, grants from NIH/NIAID, grants from NIH/NIA, grants from UpToDate, Inc., personal fees from Biomarin, Inc., personal fees for lectures/presentations: CME companies, Clinical Care Options companies, Mentor Planning and Practice Point, personal fees from DKBMed for communications, personal fees for academic work from Geisinger Health Systems and St. Luke’s/Roosevelt, personal fees from Ken Krayesek Law Offices, personal fees from Duke University, outside the submitted work; MH: grants from Gilead Sciences, grants from AbbVie, outside the submitted work; EG: personal fees from Gilead Scientific Advisory Board, personal fees from AbbVie Scientific Advisory Board, personal fees from Janssen Scientific Advisory Board, outside the submitted work; MN: grants, personal fees and non-financial support from AbbVie, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from Gilead Sciences, payment or honoraria: Gilead, AbbVie, BMS and MSD, travel support: Gilead, AbbVie, BMS and MSD, personal fees from MBS DMSB or equivalent, outside the submitted work; PI: grants and personal fees from Gilead Sciences, personal fees from AbbVie, personal fees from ViiV, outside the submitted work; JG: grants and personal fees from AbbVie, grants and personal fees from Gilead Sciences, grants and personal fees from Merck, grants and personal fees from Cepheid, grants from Hologic, grants from Indivior, payment or honoraria: AbbVie, Gilead Sciences and Cepheid, travel support: AbbVie, Gilead Sciences and Cepheid, receipt of testing equipment and cartridges from Cepheid, receipt of testing reagents from Hologic, outside the submitted work; KP: grants from Gilead sciences Australia and ViiV Healthcare Australia, outside the submitted work; GD: grants, personal fees and non-financial support from Gilead Sciences, AbbVie and Merck, grants from Bristol-Myers Squibb, outside the submitted work; DS, MM, TA and PM: nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: More than 292 million people are living with hepatitis B worldwide and are at risk of death from cirrhosis and liver cancer. The World Health Organization (WHO) has set global targets for the elimination of viral hepatitis as a public health threat by 2030. However, current levels of global investment in viral hepatitis elimination programmes are insufficient to achieve these goals., Methods: To catalyse political commitment and to encourage domestic and international financing, we used published modelling data and key stakeholder interviews to develop an investment framework to demonstrate the return on investment for viral hepatitis elimination., Results: The framework utilises a public health approach to identify evidence-based national activities that reduce viral hepatitis-related morbidity and mortality, as well as international activities and critical enablers that allow countries to achieve maximum impact on health outcomes from their investments - in the context of the WHO's 2030 viral elimination targets., Conclusion: Focusing on hepatitis B, this health policy paper employs the investment framework to estimate the substantial economic benefits of investing in the elimination of hepatitis B and demonstrates how such investments could be cost saving by 2030., Lay Summary: Hepatitis B infection is a major cause of death from liver disease and liver cancer globally. To reduce deaths from hepatitis B infection, we need more people to be tested and treated for hepatitis B. In this paper, we outline a framework of activities to reduce hepatitis B-related deaths and discuss ways in which governments could pay for them., Competing Interests: Conflict of interest JH has received investigator-initiated funding and speaker fees from Gilead Sciences. AHS reports grants to her institution from ViiV Healthcare. ETH is the former director of the Medicines Patent Pool. NS has received investigator-initiated research funding from Gilead Sciences. AP has received investigator-initiated research funding from Gilead Sciences, MSD and AbbVie, and honoraria from Gilead Sciences. JVL reports grants and personal fees from AbbVie, Gilead Sciences and MSD, personal fees from CEPHEID and Janssen, all outside the submitted work. MS is principal investigator in an investigator-initiated trial sponsored by Gilead Sciences (received no PI fees, trial closed April 17th 2019) and reports an educational grant to travel to EASL 2019 (Gilead Sciences). SJH received honoraria from Gilead, unrelated to submitted work. AJT is advisory board member for Gilead Sciences, Arbutus Biopharma, AbbVie, BMS, Bayer, Roche, Ipsen, Eisai, Immunocore Ltd, Clear B Therapeutics, ViR therapeutics and has received speaker fees and investigator-initiated funding from Gilead Sciences, AbbVie and BMS. MH's Institute receives investigator initiated research funding from Gilead Sciences, Abbvie and BMS. JH received the Gilead Sciences Australia fellowship (2017). DW, CK, RA, RBL, MB, LA, AG, SH, RH, WL, RBM, SO, RP, MS, CWS, MT, ESS have nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Treatment programs for people who inject drugs (PWID), including prisoners, are important for achieving hepatitis C elimination targets. There are multiple barriers to treatment of hepatitis C in prisons, including access to specialist physicians, testing and antiviral therapy, short prison sentences, and frequent inter-prison transfer. We aimed to assess the effectiveness of a nurse-led model of care for the treatment of prisoners with hepatitis C., Methods: A statewide program for assessment and management of hepatitis C was developed in Victoria, Australia to improve access to care for prisoners. This nurse-led model of care is supported by telemedicine to provide decentralized care within all prisons in the state. We prospectively evaluated the feasibility and efficacy of this nurse-led model of care for hepatitis C within the 14 adult prisons over a 13-month period. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) using per protocol analysis., Results: There were 416 prisoners included in the analysis. The median age was 41 years, 90% were male, 50% had genotype 3 and 44% genotype 1 hepatitis C and 21% had cirrhosis. Injecting drug use was reported by 68% in the month prior to prison entry, 54% were receiving opioid substitution therapy, and 86% reported never previously engaging with specialist HCV care. Treatment duration was 8 weeks in 24%, 12 weeks in 59%, and 24 weeks in 17% of treatment courses. The SVR12 rate was 96% (301/313) per protocol. Inter-prison transfer occurred during 26% of treatment courses but was not associated with lower SVR12 rates. No treatment-related serious adverse events occurred., Conclusion: Hepatitis C treatment using a decentralized, nurse-led model of care is highly effective and can reach large numbers of prisoners. Large scale prison treatment programs should be considered to support hepatitis C elimination efforts., Lay Summary: There is a high burden of hepatitis C infection among prisoners worldwide. Prisoners who continue to inject drugs are also at risk of developing new infections. For this reason, the prison setting provides an opportunity to treat those people at greatest risk of infection and to stop transmission to others. We developed a new method of providing hepatitis C treatment to prisoners, in which nurses rather than doctors assessed prisoners locally at each prison site. Treatment was safe and most prisoners were cured. Such programs will contribute greatly to achieving the World Health Organization's hepatitis C elimination goals., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background & Aims: In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization's HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring., Methods: We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections., Results: The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely., Conclusion: HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached., Lay Summary: In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Adherence to HCV therapy impacts sustained virological response (SVR) but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (≥80% of PEG-IFN doses, ≥80% treatment), on-treatment adherence, and treatment completion in a study of treatment of recent HCV infection (ATAHC)., Methods: Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180μg/week, n=74) and those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35), for a planned 24 weeks. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence., Results: A total of 109 out of 163 patients received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed ≥1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23, and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76) of cases, respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29, p=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those patients with ≥80/80 PEG-IFN adherence (67% vs. 35%, p=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%, p=0.309). SVR in those patients discontinuing therapy between 0-4, 5-19, 20-23, and 24 weeks was 9%, 33%, 43%, and 76%, respectively (p<0.001)., Conclusions: High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)