Abstract
Following the discovery of hepatitis C virus (HCV) in 1989, 3 decades of basic, translational, and clinical research culminated in the development of direct-acting antiviral (DAA) ...therapy—curative oral treatment for HCV infection. The availability of DAA therapy revolutionized HCV clinical management, including acute (duration of infection <6 mo) and recent (duration of infection <12 mo) infection. Several DAA regimens, including the contemporary pan-genotypic combinations of sofosbuvir-velpatasvir and glecaprevir-pibrentasvir, have been shown to be safe and effective among people with acute and recent HCV infection, highlighting their potential in an HCV controlled human infection model. This article describes the natural history and management of acute and recent HCV infection in the era of DAA therapy and outlines a strategy for use of DAA therapies in the setting of an HCV controlled human infection model.
This article describes the natural history and management of acute and recent HCV infection in the era of DAA therapy and outlines a strategy for use of DAA therapies in the setting of an HCV controlled human infection model.
Background
Regular monitoring and treatment of chronic hepatitis B (CHB) are known to reduce the risk of hepatocellular carcinoma. We sought to describe patterns of monitoring and treatment among ...adults diagnosed with CHB in Australia.
Methods
Population-based prospective cohort study of Australian adults aged 45 + years followed by record-linkage to hepatitis B notifications, monitoring and treatment. Proportions of those with CHB who: had viral load test; were dispensed antiviral treatment; and had ultrasound surveillance were estimated. The characteristics associated with viral load test and ultrasound surveillance were examined using logistic regression.
Results
A total of 576 adults with CHB were identified. From 2008 to 2015, 14.8% (85/576) had at least one viral load test recorded every 2 years and 19.1% (110/576) had at least one antiviral treatment recorded, 19.9% (58/292) had at least one ultrasound recorded every year among those eligible for ultrasound surveillance. A record of having at least one viral load test every 2 years was more likely among adults born in Asia compared to Australian-born (21.4% vs 8.6%), those notified in more recent years compared to earlier years, and those on antiviral treatment compared to not on treatment. Increasing proportions of cases had records of at least one viral load test over time (2008: 10.5%, 2015: 27.2%) and at least one antiviral treatment (2008: 3.0%, 2015: 18.5%).
Conclusions
In Australian adults, estimates of care interventions for CHB management have increased over time but still fall short of targets recommended in the National Hepatitis B Strategy.
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 F1-score for the model were 96.3%, 96.5%, 96.3%, 96.3% and 96.3%, respectively. Nationally, 95,272 individuals initiated DAAs, with treatment uptake declining from 32,454 in 2016 to 6,566 in 2021. Of those treated, 6,980 (7%) were retreated. Our model classified 51.8% (95% CI 46.7–53.6%; n = 3,614) of cases as reinfection and 48.2% (95% CI 46.4–53.3%; n = 3,366) as treatment failure. Retreatment for reinfection increased steadily over the study period from 14 in 2016 to 1,092 in 2020, stabilising in 2021. Retreatment for treatment failure increased from 73 in 2016 to 1,077 in 2019, then declined to 515 in 2021. Among individuals retreated for treatment failure, 50% had discontinued initial treatment.
We 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.
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•Seven percent of people treated for HCV in Australia were retreated.•Machine learning was used to classify retreatments based on national administrative data.•Overall, 52% of retreatment was for reinfection and 48% was for treatment failure.•Retreatment for reinfection increased over time, reflecting increasing numbers of people at-risk for reinfection following cure.•Retreatment for treatment failure increased when salvage DAAs became available.
High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to ...estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence.
HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence.
57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio aOR 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98).
These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination.
To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.
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•People who inject drugs are a key population for hepatitis C elimination.•Australia has provided universal access to direct-acting antiviral therapy since 2016.•Data linkage was used to assess population-level direct-acting antiviral uptake.•Those with evidence of recent drug dependence had the highest treatment uptake.•Despite higher direct-acting antiviral uptake among those with recent drug dependence, gaps remain.
Abstract
Background
Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting ...antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access.
Methods
The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed.
Results
Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male 80% gay and bisexual men,, 13% cirrhosis, 80% history of injecting drug use 39% currently injecting). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94).
Conclusions
High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible.
Clinical Trials Registration
NCT02102451.
Linkage to care and unrestricted access to direct-acting antiviral therapy have facilitated rapid hepatitis C virus (HCV) treatment scale-up among people living with human immunodeficiency virus in Australia, reducing HCV viremic prevalence, and highlighting the potential population-level impact of HCV treatment-as-prevention.
Abstract
The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable ...direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective “test-and-treat” strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.
The scale-up of direct-acting antiviral (DAA) therapy and introduction of preexposure prophylaxis (PrEP) has changed the epidemiology of sexually acquired hepatitis C virus (HCV) amongst HIV-positive ...and HIV-negative MSM.
Sexually acquired HCV continues to occur predominantly amongst HIV-positive MSM. Despite an increased uptake of DAA therapy the incidence of acute HCV has not declined consistently amongst HIV-positive MSM, likely a result of high infection and reinfection rates. Increasing cases of sexually acquired HCV have been reported amongst HIV-negative MSM accessing PrEP. Despite a lower prevalence of HCV at baseline, HIV-negative MSM accessing PrEP have an equally high overall incidence of HCV compared with HIV-positive MSM during follow-up. Behavioural factors (high-risk sexual behaviours and sexualized drug use) appear to be driving this HCV epidemic amongst MSM and effective behavioural interventions and early identification of reinfections are essential to control the HCV epidemic amongst MSM.
An improved understanding of the epidemiology of sexually acquired HCV will allow implementation of more effective public health interventions to control the transmission of HCV amongst HIV-positive and HIV-negative MSM.
•Trusting relationships with HIV physicians enhanced HCV treatment experience.•Perceptions of how HCV infection was acquired was important for some participants.•Understandings of HCV (re)infection ...from high risk sexual activity were limited.•Most participants did not address HCV (re)infection in the context of PrEP.•Findings underscore key roles for peer workers in behavioural risk interventions.
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.
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.
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.
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.
Our Australian hospital tested almost 22 000 symptomatic people over 11 weeks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multiplex polymerase chain reaction (PCR) assay. ...Following travel bans and physical distancing, SARS-CoV-2 and other respiratory viruses diagnoses fell dramatically. Increasing rhinovirus diagnoses as social control measures were relaxed may indirectly indicate an elevated risk of coronavirus disease 2019 (COVID-19) resurgence.
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