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Objectives: The objective of this study was to estimate prevalence of hepatitis C virus (HCV) exposure and infection among Indigenous and tribal populations globally., Study Design: Systematic review and meta-analysis., Methods: We systematically searched bibliographic databases and grey literature (1/01/2000-16/06/2022). Prevalence estimates were synthesised overall, by World Health Organization region and HCV-risk group. For studies with comparator populations, prevalence ratios were estimated and pooled., Results: Ninety-two studies were included. Globally, among general Indigenous and tribal populations, the median prevalence of HCV antibody (HCV Ab) was 1.3% (interquartile range [IQR]: 0.3-3.8%, I 2  = 98.5%) and HCV RNA was 0.4% (IQR: 0-1.3%, I 2  = 96.1%). The Western Pacific Region had the highest prevalence (HCV Ab: median: 3.0% [IQR: 0.4-11.9%], HCV RNA: median 5.6% [IQR: 2.0-8.8%]). Prevalence was highest in people who injected drugs (HCV Ab: median: 59.5%, IQR: 51.5-67.6%, I 2  = 96.6%; and HCV RNA: median: 29.4%, IQR: 21.8-35.2%, I 2  = 97.2%). There was no association between HCV Ab prevalence and Indigenous/tribal status for general populations (prevalence ratio = 0.91; 95% CI: 0.56, 1.49) or key risk groups., Conclusions: Indigenous and tribal peoples from the Western Pacific Region and recognised at-risk sub-populations had higher HCV prevalence. HCV prevalence showed no association with Indigenous/tribal status. However, this review was limited by heterogeneity and poor quality of constituent studies, varying definitions of Indigenous/tribal status, regional data gaps, and limited studies on chronic infection (HCV RNA). Comprehensive quality evidence on HCV epidemiology in Indigenous and tribal peoples is needed to tailor preventive and treatment interventions so these populations are not left behind in elimination efforts., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Stigma has negative consequences for the health of people who inject drugs and people living with hepatitis C virus (HCV). This study evaluated factors associated with stigma related to injecting drug use (IDU) or HCV and those associated with being treated negatively by health workers., Methods: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire including IDU- and HCV-related stigma, and negative treatment by health workers. Logistic regression was used to identify factors associated with experiencing stigma and negative treatment in a cross-sectional sample., Results: Of 1,211 participants, 31% were women, 64% had injected drugs in the previous month, and 65% had been diagnosed with HCV. IDU-related stigma was reported by 57% of participants and was associated with being a woman, higher than Year 10 education, homelessness, opioid agonist treatment, recent injecting, overdose history, hospitalisation for drug use, and unknown HCV status. HCV-related stigma was reported by 34% of participants diagnosed with HCV and was associated with being a woman, homelessness, receptive needle/syringe sharing, arrest for drug use/possession, and recent HCV testing. Negative treatment from health workers was reported by 45% of participants and was associated with being a woman, receptive needle/syringe sharing, hospitalisation for drug use, and arrest for drug use/possession., Discussion and Conclusions: Results highlight important intersections and disparities in stigmatising experiences among people who inject drugs. Considering these intersections can assist health services provide more inclusive care., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TB has received speaker fees from Gilead Sciences. JG reports personal fees from Abbott, Abbvie, Cepheid, Gilead Sciences, and Roche and grants from Abbvie, bioLytical, Cepheid, Gilead Sciences, and Hologic, outside the submitted work. GD reports grants from AbbVie and Gilead Sciences. LD has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, Mundipharma and Seqirus. HV has received honorarium from Gilead Sciences. All remaining authors have no potential conflicts to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Evaluating gender-specific trends in hepatitis C virus (HCV) treatment uptake among men and women who inject drugs is crucial for ensuring equitable progress towards HCV elimination. This study aimed to quantify differences in testing, treatment, and current HCV infection between men and women who inject drugs., Method: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia recruited from May 2018-September 2019 (wave 1) and November 2019-April 2021 (wave 2). Participants completed a questionnaire including self-reported HCV testing and treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to compare the factors associated with self-reported HCV testing and treatment and current HCV infection for men and women who inject drugs., Results: Among 2,395 participants enrolled in ETHOS Engage, 66% (n = 1,591) were men, 33% (n = 786) women, and <1% (n = 18) did not identify as a man or woman. HCV testing history and current infection were similar among men and women. Among men or women ever eligible for HCV treatment (ever chronic HCV) (n = 1,242), women were less likely to report a history of HCV treatment compared to men (227/352, 64% vs. 631/890, 71%; p = 0.03). Among women, those aged <45 were less likely to report HCV testing (aOR: 0.57, 95%CI: 0.36, 0.90), treatment (aOR: 0.47, 95%CI: 0.29, 0.77), and more likely to have HCV infection (aOR: 1.48, 95%CI: 1.00, 2.20) CONCLUSION: Among women, those of childbearing age (<45) were less likely to report testing and treatment and were more likely to have current HCV infection. Women <45 years old should be a priority population for HCV care. Services that interface with these women should be optimised to enhance HCV testing and treatment., Competing Interests: Declaration of competing interest HV has received honoraria from Gilead Sciences. JG is a consultant/advisor and has received research grants from Abbvie, Abbott, Biolytical, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, Merck/MSD, and Roche. GD has received research grants from Gilead, Abbvie, and Merck. LD has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, Mundipharma and Seqirus. PR has received research funding from Gilead Sciences. CH has research grants from Indivior. All remaining authors have no potential conflicts to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hepatitis C (HCV) is highly prevalent in First Nations communities globally. Barriers in the uptake of testing and treatment create challenges to realise elimination of HCV in these communities. In efforts to reduce barriers to testing and treatment, the SCALE-C study implemented an HCV test-and-treat intervention integrating point-of-care HCV testing and FibroScan®. SCALE-C was carried out at four Aboriginal Community Controlled Health Services (ACCHS; renowned for providing culturally safe care) in four regional towns in Australia. This qualitative analysis sought to understand healthcare provider and patient perceptions of acceptability of a community-based HCV test-and-treat intervention within ACCHS., Methods: Semi-structured interviews were undertaken with 23 patient participants and 14 healthcare personnel (including Aboriginal Health Workers/Practitioners, nurses, general practitioners, and practice managers) from across the four ACCHS involved in SCALE-C. A coding framework was developed among study authors and informed by Sekhon's Theoretical Framework of Acceptability., Results: The SCALE-C intervention enabled opportunities for healthcare providers to listen to patients, and for patients to feel heard (affective attitude). HCV testing was opportunistic and often occurred outside of the allocated SCALE-C clinical hours (burden). For patients, HCV testing within SCALE-C was viewed as a moral responsibility and ensured protection of self and others (ethicality). For personnel, SCALE-C (including following up visits) was regarded as an opportunity to engage with patients especially those with complex health needs which may be unrelated to HCV risk factors (ethicality). Patients and personnel widely regarded the SCALE-C intervention to be effective, and the test-and-treat model was preferable for both patients and personnel., Conclusion: The SCALE-C intervention was broadly perceived to be acceptable among both healthcare providers and patients within ACCHS. Whilst the prioritisation of HCV was viewed as increasing patient engagement, it was also regarded as an opportunity for addressing other healthcare needs within Aboriginal communities. HCV test-and-treat models of care delivered by ACCHS simplify the HCV care pathway and ensure all HCV care is provided in a culturally safe setting (e.g., patients did not need to attend external services such as pathology)., Competing Interests: Declaration of competing interest LL has received speaker fees from AbbVie and Gilead Sciences. MB, JW, EF, and SH-H have nothing to declare. MM reports salary support from the Australian National Health and Medical Research Council Early Career Fellowship. CT has received speaker fees from AbbVie and Gilead Sciences., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required., Competing Interests: Declaration of interests SSS declares institutional grant support from the National Institutes of Health, Elton John AIDS foundation, US President's Emergency Plan for AIDS relief and US Agency for International Development, Gilead Sciences, and Abbott Laboratories, and honoraria from Gilead Sciences and Abbott Laboratories. NAT declares institutional grant support from the National Institutes of Health, GlaxoSmithKline, Genetech-Roche, Helio Health, Durect Corp, Gilead Sciences, and Eiger Pharmaceuticals, and consulting fees from Moderna. GJD declares institutional grant support from Gilead Sciences, AbbVie, and Merck. MM declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Globally, treatment uptake for hepatitis C virus (HCV) infection among HIV-HCV coinfected men who have sex with men (MSM) has substantially increased since the advent of interferon-free direct-acting antivirals (DAA). However, HIV-positive MSM who engage in high risk behaviours are at an increased risk of HCV reinfection post-treatment. The aim of this study was to investigate perceptions of HCV diagnosis, treatment and reinfection risk among HCV-HIV coinfected MSM who engage in drug use and/or high risk sexual behavior in Sydney, Australia., Methods: Participants were recruited from the Control and Elimination within AuStralia of HEpatitis C from people living with HIV (CEASE) cohort (n=402) who reported engaging in drug use and/or high risk sexual behavior for transmission of HCV infection. Participants were interviewed about their perceptions of HCV diagnosis, treatment, and reinfection risk. Interview data were transcribed, coded, and analyzed thematically., Results: Of 33 participants interviewed (mean age 49 years), many participants were 'shocked' by their HCV diagnosis. Participants who believed they acquired HCV infection through sexual exposure felt it was important that their healthcare practitioner agreed with their perspective to mitigate stigmatizing experiences. Overall, participants expressed high satisfaction with their treatment experience due to long-standing therapeutic relationships with their HIV physician. Many participants expressed knowledge of how to prevent HCV reinfection from injection drug use, yet other than condom usage, most were unsure how to reduce high risk sexual activity with such discussions occurring less frequently with healthcare practitioners., Conclusion: Findings indicate that MSM who engage in drug use and high risk sexual activity would benefit from additional education on reducing reinfection risk through sexual activity and services to reduce substance use, if requested., Competing Interests: Declarations of Interest ADM has nothing to declare. CT has received speaker fees from Abbvie and Gilead and grant funding from Merck. GVM has received speaker fees from Gilead, Abbvie, and Janseen; has received research funding from Gilead, Abbvie and Janssen; and has received advisory board payments from Gilead and Abbvie. MM and GVM are supported by the Australian National Health and Medical Research Council (NHMRC)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Injecting-related skin and soft tissue infections (SSTIs) are a preventable cause of inpatient hospitalisation among people who inject drugs (PWID). This study aimed to determine the prevalence of hospitalisation for SSTIs among PWID, and identify similarities and differences in factors associated with hospitalisation for SSTIs versus non-bacterial harms related to injecting drug use., Methods: We performed cross-sectional analyses of baseline data from an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Logistic regression models were used to identify factors associated with self-reported hospitalisation for (1) SSTIs (abscess and/or cellulitis), and (2) non-bacterial harms related to injecting drug use (e.g., non-fatal overdose; hereafter referred to as non-bacterial harms), both together and separately., Results: 1851 participants who injected drugs in the previous six months were enrolled (67% male; 85% injected in the past month; 42% receiving opioid agonist treatment [OAT]). In the previous year, 40% (n = 737) had been hospitalised for drug-related causes: 20% (n = 377) and 29% (n = 528) of participants were admitted to hospital for an SSTI and non-bacterial harm, respectively. Participants who were female (adjusted odds ratio [aOR]: 1.53, 95% CI: 1.19-1.97) or homeless (aOR: 1.59, 95% CI: 1.16-2.19) were more likely to be hospitalised for an SSTI, but not a non-bacterial harm. Both types of hospitalisation were more likely among people recently released from prison., Conclusions: Hospitalisation for SSTIs is common among PWID. Community-based interventions to prevent SSTIs and subsequent hospitalisation among PWID will require targeting of at-risk groups, including women, people experiencing homelessness, and incarcerated people upon prison release., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between 2018-2019 and 2019-2021., Methods: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to identify factors associated with current HCV infection and historic HCV treatment., Results: 2,395 individuals were enrolled across the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previous month). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCV treatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio [aOR] 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with current infection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recently injecting drugs (vs. >12 months ago; previous month

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: Direct acting antiviral (DAA) therapy is highly effective for hepatitis C virus (HCV) infection, but reinfection following treatment may compromise benefits of cure. This study assessed the real-world effectiveness of treatment for reinfection., Methods: Real-world effectiveness of antiviral therapy in chronic hepatitis C (REACH-C) is an observational study evaluating treatment outcomes following sequential DAA initiations across 33 health services in Australia between March 2016-June 2019. Reinfection was defined by post-treatment genotype switch or HCV viraemia after sustained virologic response (SVR12)., Results: Of the 10,843 individuals initiating DAA therapy post-treatment viraemia was reported in 526 of whom 99 were reinfections. Treatment for reinfection occurred in 88 individuals. In those with available treatment outcomes, SVR12 was similar to initial treatment in the overall REACH-C cohort (95% vs 95%; p = 0.745) and comparable across primary, tertiary, and prison settings. Classifying unknown treatment outcomes as failures, SVR12 for treatment of reinfection was lower than initial treatment in REACH-C (67% vs 81%; p = 0.002), due to higher lost to follow-up., Conclusions: Treatment of reinfection is highly effective and can be delivered in non-specialist settings. Access to treatment for reinfection in high-risk populations is crucial to HCV elimination., Competing Interests: Declarations of Interest GVM reports grants from Gilead Sciences and grants from AbbVie. GJD reports grants, personal fees, and nonfinancial support from AbbVie, Gilead, Merck, Bristol-Myers Squibb, and Roche; grants and personal fees from Janssen; personal fees and nonfinancial support from Gilead Sciences; and personal fees from GlaxoSmithKline and Abbott Diagnostics. DI reports fees from Gilead, Merck, BMS, and AbbVie. PR reports fees for educational talks from Gilead Sciences, Merck Sharp & Dohme, and AbbVie and is on the advisory board for Merck Sharp & Dohme. AB reports sponsorship from Gilead to participate in online HCV medical educational modules. JDo reports grants to his institution for investigator initiated research and consulting fees from Gilead Sciences, Merck/MSD, AbbVie and Bristol-Myers Squibb. JO reports speaker fees from Gilead and BMS. MM reports grants from Gilead Sciences. JC/JY/BH/JH/JDa/PM report none., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: Mathematical modeling of viral kinetics has been shown to identify patients with chronic hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antiviral (DAA) treatment. However, modeling therapy duration has yet to be evaluated in recently infected individuals. The aim of this study was to retrospectively examine whether modeling can predict outcomes of six-week sofosbuvir (SOF) and weight-based ribavirin (R) therapy in individuals with recent HCV infection., Methods: Modeling was used to estimate viral host parameters and to predict time to cure for 12 adults with recent HCV infection (<12 months of infection) who received six weeks of treatment with SOF + R., Results: Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment., Conclusions: The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection., Competing Interests: Declaration of competing interest GVM advises, is on the speakers' bureau, and received grants from Gilead. She is on the speakers’ bureau and received grants from AbbVie and Bristol-Myers Squibb. She received grants from Janssen. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT)., Methods: We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies., Results: Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates., Conclusion: HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment., Lay Summary: Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule., Methods: In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%., Results: Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported., Conclusions: In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority., Trial Registration: clinicaltrials.gov Identifier: NCT03117569., Lay Summary: Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%)., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Uptake of hepatitis C virus (HCV) testing remains inadequate globally. Simplified point-of-care tests should enhance HCV diagnosis and elimination. We aimed to assess the acceptability of finger-stick and venepuncture HCV RNA testing among people who inject drugs (PWID)., Methods: Participants were enrolled in an observational cohort study with recruitment at 13 sites between June 2016 and February 2018. Capillary whole-blood collected by finger-stick and plasma collected by venepuncture were performed for Xpert ® HCV viral load testing. Participants completed a questionnaire on acceptability of, and preferences for, blood collection methods., Results: Among 565 participants (mean age, 44 years; 69% male), 64% reported injecting drugs in the last month, and 63% were receiving opioid substitution treatment. Eighty three percent reported that finger-stick testing was very acceptable. Overall, 65% of participants preferred finger-stick over venepuncture testing, with 61% of these preferring to receive results in 60 min. The most common reason for preferring finger-stick over venepuncture testing was it was quick (62%) followed by venous access difficulties (21%). The main reasons for preferring venepuncture over finger-stick testing were that it was quick (61%) and accurate (29%). Females were more likely to prefer finger-stick testing than males (adjusted OR 1.96; 95% CI 1.30, 2.99; p = 0.002). Among people with recent (previous month) injecting drug use, Aboriginal and/or Torres Strait Islander people were less likely than non-Aboriginal people to prefer finger-stick testing (adjusted OR 0.57; 95% CI 0.34, 0.9; p = 0.033)., Conclusions: Finger-stick whole-blood collection is acceptable to people who inject drugs, with males and Aboriginal and/or Torres Strait Islander people with recent injecting drug use less likely to prefer finger-stick testing. Further research is needed to evaluate interventions integrating simplified point-of-care HCV testing to engage people in care in a single-visit, thereby facilitating HCV treatment scale-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Gastrointestinal mucormycosis is an uncommon, life-threatening, angioinvasive infection with only one previous report of disease involving the jejunum. We present a case of invasive jejunal mucormycosis and review the literature, highlighting the rare clinical presentation and the value of molecular diagnostic methods. Given the global increase in patient populations at risk of mucormycosis, clinicians need to maintain a high index of suspicion and perform timely and appropriate evaluation to improve patient outcome.