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Background: New technologies and therapies allow the possibility of a single-visit test and treat model for hepatitis C virus (HCV), addressing some of the barriers to care faced by people who inject drugs. Methods: The TEMPO Pilot Study was an interventional cohort study evaluating a single-visit test and treat intervention among people with recent injecting drug use at a one peer-led needle and syringe program (NSP) in Sydney, Australia between September 2019 and February 2021. This analysis evaluated awareness of HCV status and agreement of self-report with HCV RNA test results. The analysis also assessed acceptability of: modality of result delivery, modality of blood sampling, site of treatment, and duration of treatment. Results: Among 101 participants (median age 43; 31% female), 100 had a valid HCV RNA test result and 27% (27/100) were HCV RNA detectable. Overall, 65% (65/100) were aware of their status. Among people with a positive HCV RNA result, 48% (13/27) were aware of their status. People preferred same-day HCV test results (95%, 96/101), and preferred to receive results in person (69%, 70/101). Receiving treatment at an NSP was acceptable (100%, 101/101) and 78% (79/101) were willing to discuss their health with a peer NSP worker. Conclusion: Half of people with current HCV infection were aware of their status. The high acceptability of simplified testing and treatment pathways delivered at NSPs indicates that this is an appropriate strategy to improve HCV awareness and treatment uptake in this population. [ABSTRACT FROM AUTHOR]

Background The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). Methods Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. Results Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2–2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6–6.3) overall and 17.9/100 person-years (95% CI, 5.8–55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. Conclusions These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. Clinical Trials Registration NCT02336139 and NCT02498015. [ABSTRACT FROM AUTHOR]

Background This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. Results Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P =.005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28–4.82]), unstable housing (OR, 2.18 [95% CI, 1.01–4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47–5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P =.174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P =.897). Conclusions This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence. [ABSTRACT FROM AUTHOR]

Background In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment. Methods SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016–2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations. Results At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test–Consumption; range, 1–12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92–0.99) and sharing (OR, 0.87; 95% CI, 0.80–0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94–1.02) or alcohol use (OR, 0.99; 95% CI, 0.95–1.04). Conclusions Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use. Clinical Trials Registration SIMPLIFY, NCT02336139; D3FEAT, NCT02498015. [ABSTRACT FROM AUTHOR]

Background and aims: Australia is currently on track to meet the World Health Organization (WHO) global hepatitis C virus (HCV) elimination goals by 2030, reflecting universal subsidized access to testing and direct‐acting antiviral (DAA) treatment. In New South Wales, DAA treatment in prisons has scaled‐up substantially, with 1000 prisoners treated in 2017. However, HCV prevalence and incidence in this setting is high, which could undermine elimination efforts. This study aimed to test the preventative effects of DAA treatment scale‐up, opiate substitution treatment (OST) and needle and syringe programme (NSP) strategies for prisons. Design Modelling study using an individual‐based mathematical model of a typical prison setting. The model was calibrated against Australian epidemiological data sets and executed in‐prison events for each individual daily, including movements between prisons, changes in risk behaviour and uptake of prevention measures such as OST and NSP, as well as DAA treatment. Scenarios were projected from 2018 to 2030. Setting: New South Wales prisons. Participants: New South Wales prisoners. Measurements Variables including prison populations, prevalence and incidence rate were calculated. Prisoners were described by demographic characteristics, HCV infection history, risk behaviours and accessing treatment and prevention measures in varied security settings. Findings Increasing the number of prisoners treated for HCV to 2000 annually was projected to reduce the HCV incidence rate to 8.69 [95% confidence interval (CI) = 8.17, 9.20] per 100 person‐years (100 p.y.). Combined treatment and prevention strategies were necessary to reduce the projected incidence rate to 5.22 (95% CI = 5.13, 5.52) per 100 p.y. Considering the expected reductions in the prevalence of chronic HCV in the Australian community, incidence rate was predicted to drop to 0.93 (95% CI = 0.92, 0.98) per 100 p.y. by 2030. Conclusions: This model, which simulates prison scenarios to inform Australia's national hepatitis C virus elimination efforts, suggests that continued direct‐acting antiviral (coverage in the community combined with a moderate increase of direct‐acting antiviral treatments in prisons, and introduction of improved harm reduction via opiate substitution treatment and/or needle and syringe programmes, makes hepatitis C virus elimination feasible in Australian prisons. [ABSTRACT FROM AUTHOR]

Summary: Subsidized direct‐acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32 600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016‐2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub‐populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN‐based) scenario. During 2016‐2030, we estimated an intermediate DAA treatment scenario (2016, 32 600 treated; 2017, 21 370 treated; 2018 17 100 treated; 2019 and beyond, 13 680 treated each year) would avert 40 420 new HCV infections, 13 260 liver‐related deaths (15 320 in viraemic; −2060 in cured) and 10 730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN‐based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver‐related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15 years. The pre‐DAA escalation in those with advanced liver disease makes the achievement of the liver‐related mortality target difficult. [ABSTRACT FROM AUTHOR]

Background and Aims: People who have recently injected drugs are a priority population in efforts to achieve hepatitis C virus (HCV) elimination. This study estimated the prevalence and number of people with recent injecting drug use living with HCV, and the proportion of people with recent injecting drug use among all people living with HCV infection at global, regional and country‐levels. Methods: Data from a global systematic review of injecting drug use and HCV antibody prevalence among people with recent (previous year) injecting drug use were used to estimate the prevalence and number of people with recent injecting drug use living with HCV. These data were combined with a systematic review of global HCV prevalence to estimate the proportion of people with recent injecting drug use among all people living with HCV. Results: There are an estimated 6.1 million [95% uncertainty interval (UI) = 3.4–9.2] people with recent injecting drug use aged 15–64 years living with HCV globally (39.2% viraemic prevalence; UI = 31.6–47.0), with the greatest numbers in East and Southeast Asia (1.5 million, UI = 1.0–2.1), eastern Europe (1.5 million, UI = 0.7–2.4) and North America (1.0 million, UI = 0.4–1.7). People with recent injecting drug use comprise an estimated 8.5% (UI = 4.6–13.1) of all HCV infections globally, with the greatest proportions in North America (30.5%, UI = 11.7–56.7), Latin America (22.0%, UI = 15.3–30.4) and eastern Europe (17.9%, UI = 8.2–30.9). Conclusions: Although, globally, 39.2% of people with recent injecting drug use are living with hepatitis C virus (HCV) and 8.5% of all HCV infections occur globally among people with recent injecting drug use, there is wide variation among countries and regions. [ABSTRACT FROM AUTHOR]

Background: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection.Methods: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).Results: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8).Conclusions: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011. [ABSTRACT FROM AUTHOR]

Background: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings., Methods: A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021-2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021-2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed., Results: Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community., Conclusions: Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy., Clinical Trials Registration: NCT02064049., Competing Interests: Potential conflicts of interest. G. J. D. is a consultant/advisor for and has received research grants from Gilead, AbbVie, Merck, Bristol-Myers Squibb, and Cepheid. A. R. L. has received investigator-initiated research grants from Gilead, AbbVie, Merck, and Bristol-Myers Squibb. J. G. is a consultant/advisor and has received research grants from Gilead, AbbVie, Merck, and Cepheid. P. V. has received investigator-initiated untied grants from Gilead and honoraria from Gilead and Merck. N. K. M. has received unrestricted research grants from Gilead and Merck. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)