Association between rapid utilisation of direct hepatitis C antivirals and decline in the prevalence of viremia among people who inject drugs in Australia

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Injecting drug use: A vector for the introduction of new hepatitis C virus genotypes

Hepatitis C virus(HCV) genotypes' monitoring allows real-time insight into the dynamic changes that occur in the global epidemiological picture of HCV infection. Intravenous drug use is currently the primary driver for HCV transmission in developed and developing countries. The distribution of HCV genotypes/subtypes differs significantly between people who inject drugs(PWID) and the general population. HCV genotypes that previously exhibited a limited geographical distribution(3a,4) are becoming more prevalent in this high-risk group. Immigration from HCV-endemic countries and the evolving networks of HCV transmission in PWID influence HCV genotypes distribution in Europe. Social vulnerabilities(e.g.,unemployment,homelessness,and limited access to social and healthcare insurances systems) are important triggers for illicit drug use,which increases the associated risks of HCV infection and the frequent emergence of less prevalent genotypes. Genotype/subtype determination bears important clinical consequences in the progression of liver disease,susceptibility to antiviral therapies and the emergence of resistance-associated variants. An estimated half of the chronically HCV-infected PWID are unaware of their infection,and only one in ten of those diagnosed enter treatment. Nevertheless,PWID exhibit high response rates to new antiviral regimens,and the level of HCV reinfection is unexpectedly low. The focus of the healthcare system must be on the early detection and treatment of infection,to avoid late presentations that are associated with high levels of viremia and liver fibrosis,which may diminish the therapeutic success rate.     

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement,Point-of-Care HCV RNA Testing,and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.     

Hepatitis C virus control among persons who inject drugs requires overcoming barriers to care

Despite a high prevalence of hepatitis C virus(HCV)infection,the vast majority of persons who inject drugs(PWID)have not engaged in HCV care due to a large number of obstacles.Education about the infection among both PWID and providers remains an important challenge as does discrimination faced by PWID in conventional health care settings.Many providers also remain hesitant to prescribe antiviral therapy due to concerns about adherence and relapse to drug use resulting in reinfection.Presently,however,as a result of improvements in treatment efficacy combined with professional society and government endorsement of HCV treatment for PWID,a pressing need exists to develop strategies to engage these individuals into HCV care.In this article,we propose several strategies that can be pursued in an attempt to engage PWID into HCV management.We advocate that multidisciplinary approaches that utilize health care practitioners from a wide range of specialties,as well as co-localization of medical services,are strategies likely to result in increased numbers of PWID entering into HCV management.Pursuit of HCV therapy after stabilization through drug treatment is an additional strategy likely to increase PWID engagement into HCV care.The full impact of direct acting antivirals for HCV will only be realized if innovative approaches are pursued to engage all HCV infected individuals into treatment.     

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial

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Plan asistencial coordinado para la eliminación del virus de la hepatitis C en el centro de ayuda integral al drogodependiente (CAID)

IntroductionThe drug-injecting population has a high prevalence of hepatitis C virus (HCV) and high risk of transmission. It is a priority to establish an agile diagnostic and treatment plan.Objectives1) Assess the effectiveness of a new coordinated care plan of referral from the Comprehensive Care Centre for Drug Addicts (CAID) to specialised care and 2) Determine the prevalence of HCV, clinical characteristics, effectiveness and safety of treatment in this population.Methods1,300 serologies requested by the CAID between 1998 and 2018 were retrospectively analysed, the seroprevalence of HCV was calculated and the efficiency of the traditional CAID-specialised care referral system was evaluated. A care plan was designed and coordinated among specialists involved in diagnosis and treatment. Since October 2018, 11 patients have been included in the new plan and the performance of both referral systems was compared.ResultsWith the traditional system, 48.2% (83/172) of the patients were lost. 14.5% (172/1,300) presented positive HCV serology, compared to the general population OR = 19; 95% CI 14.3-25. The prevalence of active infection was 80.3% (90/112). The prevalence of active infection was 80.3% (90/112). Of the 11 patients referred by the new plan, 76.9% (8/11) had active infection and 100% (8/8) were treated with Direct Antiviral Agents successfully.ConclusionsThe new coordinated CAID-specialised care plan presents high effectiveness in comparison with the traditional referral system. The seroprevalence and prevalence of active infection in the CAID population is very high. Treatments with Direct Antiviral Agents are effective and safe.     

The Importance of Prisons in Achieving Hepatitis C Elimination: Insights from the Australian Experience

Following the availability of highly effective direct-acting antivirals (DAAs) to treat hepatitis C infection, the uptake of treatment by people living with hepatitis C rose dramatically in high- and middle-income countries but has since declined. To achieve the World Health Organization’s (WHO) 2030 target to eliminate hepatitis C as a public health threat among people who inject drugs, an increase in testing and treatment is required, together with improved coverage of harm reduction interventions. The population that remains to be treated in high- and middle-income countries with high hepatitis C prevalence are among the most socially disadvantaged, including people who inject drugs and are involved in the criminal justice system, a group with disproportionate hepatitis C prevalence, compared with people in the wider community. Imprisonment provides an unrivalled opportunity for screening and treating large numbers of people for hepatitis C, who may not access mainstream health services in the community. Despite some implementation challenges, evidence of the efficacy, acceptability, and cost-effectiveness of in-prison hepatitis treatment programs is increasing worldwide, and evaluations of these programs have demonstrated the capacity for treating people in high numbers. In this Perspective we argue that the scale-up of hepatitis C prevention, testing, and treatment programs in prisons, along with the investigation of new and adapted approaches, is critical to achieving WHO elimination goals in many regions; the Australian experience is highlighted as a case example. We conclude by discussing opportunities to improve access to prevention, testing, and treatment for people in prison and other justice-involved populations, including harnessing the changed practices brought about by the COVID-19 pandemic.     

New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years

Hepatitis C virus (HCV) is a global health concern associated with significant morbidity and mortality. Before the approval of second-generation direct-acting antiviral agents (DAAs), interferon therapy and liver transplantation constituted the mainstay of treatment. The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95% cure rates. The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs. Despite the unparallel efficacy observed among these novel therapies, pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally. To reduce the burden of disease worldwide, essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies. Through transparent negotiations with the pharmaceutical industry, the consideration for compassionate release of medications to promote equitable division of care is paramount. Here we provide a literature review of HCV, changes in epidemiologic trends, access issues for current therapies, and global inequities in disease burden.     

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most com-monly caused by hepatitis C virus(HCV) infection. Although people who inject drugs(PWID) are the ma-jor source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these pa-tients, and substitution therapy and active substance use are no longer contraindications for antiviral treat-ment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon com-bined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are ad-vised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchangeprograms and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treat-ment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID as-sessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strate-gies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detect-ing HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evi-dence concerning HCV infection and treatment strate-gies in PWID.     

Phylogenetic analysis of full‐length,early infection,hepatitis C virus genomes among people with intravenous drug use: the InC3 Study

Cross‐continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC³). One hundred and ninety‐two full‐length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross‐continental, full‐length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non‐Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro‐epidemics within geographically isolated communities.     

Accessing Hepatitis C patients who are difficult to reach: it is time to overcome barriers

With the arrival of simple, efficient and safe interferon‐free treatment regimens, hepatitis C virus (HCV) therapy will have the potential to be successfully used for the majority of infected patients and prevent the associated morbidity and mortality. With the current treatment uptake rates, only a very small proportion of HCV‐infected patients are reached. Paradoxically, treatment rates are lowest in the most affected at‐risk group – people who inject drugs (PWID) – which is the major driving force behind the spread of HCV infection. To conquer the increasing problem of HCV‐related liver disease, many existing but modifiable obstacles, which prevent detection, assessment and treatment uptake, have to be overcome in this population. This review article summarizes the existing literature on the most relevant barriers preventing HCV care and describes measures to overcome these obstacles.     

Influencia de los trastornos psiquiátricos y la terapia de sustitución con opiáceos en el tratamiento del virus de la hepatitis c con antivirales de acción directa en usuarios de drogas por vía parenteral

IntroductionThe effectiveness of the hepatitis C virus (HCV) treatment seems to be lower in people who inject drugs (PWID). We analyze the influence of various factors as psychiatric disorders and opioid substitution therapy (OST) on the treatment with direct-acting antivirals (DAA) in this collective.Patients and methodsThree hundred thirty-two PWID patients were treated with DAA in 12 Spanish hospitals between 2004 and 2020. They were catalogued in recent and former consumers (if the last consumption was in the last 3 years) and several variables were included, evaluating the effectiveness of the treatment according to the viral load 12 weeks after the end of the treatment with the parameter «sustained viral response» (SVR12).Results23.4% were recent consumers and 27.7% were on OST. The 41.5% had any diagnosis of psychiatric disorder. SVR12 was 84.04%, ascending to 96.21% when excluded from the analyses the patients lost to follow-up (12.7%). SVR12 was lower due to an increase in the loss to follow-up in recent consumers and other factors like OST, being in prison the last 5 years, naïve patients, generalized anxiety disorder and benzodiazepine consumption.ConclusionsThe effectiveness of the HCV treatment with DAA in PWID is similar than in general population in patients whit an appropriate follow-up. It is important to maintain a closer follow-up in patients on OST, recent consumers and those with psychiatric disorders.     

Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow‐up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework.     

Multidisciplinary managed care networks—Life‐saving interventions for hepatitis C patients

Successful hepatitis C virus (HCV) therapy depends on effective pathways of care. Over two decades, we have developed four sequential models of care latterly using a multidisciplinary managed care network to improve HCV testing, care and treatment. This was a cohort study to evaluate the effectiveness of care pathways, carried out using all HCV antibody‐positive individuals tested in a geographical region between 1994 and 2014. The study involved 3122 HCV‐positive patients. They were divided into four subgroups representing different care pathways defined by their date of HCV antibody diagnosis. The number who accessed treatment services within 1 year of diagnosis increased from 77 of 292 (26.3%) to 521 of 821 (72.9%). The rate of treatment starts within 1 year of diagnosis increased from 6 of 292 (2.0%) to 133 of 821 (16.2%), and the sustained viral response rate improved from 61.6% to 77.4%. All‐cause mortality decreased from 232 of 688 (33.7%) in subgroup A to 55 of 1207 (4.5%) in subgroup D, and multivariate analysis showed that pathway type was an independent predictor of mortality irrespective of age, sex, SVR status or HIV co‐infection with pathway in D having an odds ratio of 0.53(0.40‐0.77; P<.001) compared to pathway in A. At study end, 78% (3122) of an estimated 4000 HCV positive had been diagnosed. In total, 97.5% of HCV caseload was referred to specialist services and 89% attended for assessment. The introduction of a managed care network increased access to care and reduced all‐cause mortality.