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Background People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) infection compared with housed populations. Surveillance for HCV reinfection after successful treatment is a critical step in the care cascade, but limited data on reinfection are available among this highly marginalized group. This study assessed posttreatment reinfection risk in a real-world cohort of homeless-experienced individuals in Boston. Methods Individuals receiving HCV direct-acting antiviral treatment through Boston Health Care for the Homeless Program during 2014–2020 with posttreatment follow-up assessment were included. Reinfection was identified based on recurrent HCV RNA at 12 weeks posttreatment with HCV genotype switch or any recurrent HCV RNA following sustain virologic response. Results A total of 535 individuals were included (81% male, median age 49 years, 70% unstably housed or homeless at treatment initiation). Seventy-four HCV reinfections were detected, including 5 second reinfections. HCV reinfection rate was 12.0/100 person-years (95% confidence interval [CI]: 9.5–15.1) overall, 18.9/100 person-years (95% CI: 13.3–26.7) among individuals with unstable housing and 14.6/100 person-years (95% CI: 10.0–21.3) among those experiencing homelessness. In adjusted analysis, experiencing homelessness (vs stable housing, adjusted hazard ratio, 2.14; 95% CI: 1.09–4.20; P = .026) and drug use within 6 months before treatment (adjusted hazard ratio, 5.23; 95% CI: 2.25–12.13; P < .001) were associated with increased reinfection risk. Conclusions We found high HCV reinfection rates in a homeless-experienced population, with increased risk among those homeless at treatment. Tailored strategies to address the individual and systems factors impacting marginalized populations are required to prevent HCV reinfection and to enhance engagement in posttreatment HCV care.

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n=10843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n=56) and tertiary (n=157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per-protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p=1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11-0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64-11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15-0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralised models may increase retreatment uptake and reduce HCV-related mortality.

Background Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs). Methods The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3–6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated. Results Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval [CI]: 7.9–19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3–50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio [aHR], 4.74 [95% CI: 1.33–16.80]; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase [95% CI: .26–.64]; P Conclusions A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are ­essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons. Clinical Trials Registration NCT02064049

Australia was one of the first countries with unrestricted access to government subsidized direct-acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real-world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow-up. Real-world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH-C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention-to-treat (ITT) and per-protocol (PP) analyses. Within REACH-C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43-0.72), cirrhosis (aOR 0.52, 95% CI 0.41-0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46-0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28-0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow-up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44-2.11; IDU + OAT: aOR 1.39, 95% CI 1.11-1.74; OAT only, aOR 1.36; 95% CI 1.13-1.68) and age (aOR 0.97, 95% CI 0.97-0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow-up presents a real-world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow-up.

Population-level uptake of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, including retreatment, can be estimated through administrative pharmaceutical dispensation data. However, the reasons for retreatment are not captured in these data. We developed a machine learning model to classify retreatments as reinfection or treatment failure at a national level.Retreatment data from the REACH-C cohort (n = 10,843 treated with DAAs; n = 320 retreatments with known reason), were used to train a random forest model. Nested cross validation was undertaken to assess model performance and to optimise hyperparameters. The model was applied to data on DAA retreatment dispensed during 2016-2021 in Australia, to identify the reason for retreatment (treatment failure or reinfection).Average predictive accuracy, precision, sensitivity, specificity and FWe used a novel methodology with high classification accuracy to evaluate DAA retreatment patterns at a national level. Increases in retreatment uptake for treatment failure corresponded to the availability of pangenotypic and salvage regimens. Increasing retreatment uptake for reinfection likely reflects increasing reinfection incidence.This study used machine learning methodologies to analyse national administrative data and characterise trends in HCV retreatment due to reinfection and treatment failure. Retreatment for reinfection increased over time, reflecting increasing numbers of people at risk for reinfection following HCV cure. Increased retreatment for treatment failure corresponded to the availability of pangenotypic and salvage DAA regimens. The findings of this study can be used by public health agencies and policy makers to guide and assess HCV elimination strategies, while the novel methodology for monitoring trends in HCV retreatment has the potential to be used in other settings, and health conditions.

Objective(s) To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia. Design Prospective observational cohort study (2014-2018). Methods Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018. Results Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44-2.53). Conclusion No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.

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.