Résumé Dans les pays à revenus élevés, la majorité des infections par le virus de l’hépatite C (VHC) nouvelles et existantes se produisent chez usagers de drogues par injection (UDI). Dans de ...nombreux pays à revenus faibles et moyens, de vastes épidémies de VHC ont également émergé chez les UDI. Le fardeau des maladies hépatiques liées au VHC chez les UDI est en augmentation, mais le recours au traitement reste extrêmement faible. Il existe un certain nombre de barrières aux soins qui doivent être évaluées et auxquelles il faut s’attaquer de façon systématique, pour faire en sorte que les UDI aient accès aux traitements. Le développement rapide d’agents antiviraux à action directe (AAD) sans interféron pour traiter l’infection par le VHC a suscité un optimisme considérable dans le domaine du VHC, faisant naître l’espoir réaliste de l’accès à une intervention thérapeutique à l’efficacité optimale, offrant des régimes thérapeutiques entièrement oraux, de courte durée et bien tolérés. En outre, il a été clairement démontré que le traitement du VHC est sûr et efficace dans un large éventail d’établissements offrant des soins multidisciplinaires. Étant donné l’importance des maladies liées au VHC chez les UDI, il est urgent de développer des stratégies visant à intensifier l’évaluation et le traitement du VHC dans ce groupe. Ces recommandations démontrent que le traitement chez les UDI est réalisable et apportent un cadre de travail pour l’évaluation et les soins du VHC. Des recherches complémentaires sont nécessaires pour évaluer les stratégies visant à intensifier le dépistage, les liens vers les soins, le traitement, l’observance, la guérison virale et pour prévenir la réinfection par le VHC chez les UDI, en particulier du fait que de nouveaux traitements AAD sans interféron pour le traitement de l’infection par le VHC deviennent disponibles.
There are concerns around poorer response to direct-acting antiviral (DAA) therapy for hepatitis C virus infection among people who use drugs. This systematic review assessed DAA treatment outcomes ...among people with recent drug use and those receiving opioid substitution therapy.
Bibliographic databases and conference presentations were searched for observational studies and clinical trials assessing DAA treatment completion, sustained virological response (SVR), and loss to follow-up among people with recent drug use (injecting or non-injecting) and those receiving opioid substitution therapy. Meta-analysis was used to pool estimates and meta-regression to explore heterogeneity.
38 eligible studies, with 3634 participants, were included. The definition of recent drug use varied across studies, with drug use in the past 6 months and at the initiation of or during DAA therapy most commonly used. Among individuals with recent injecting or non-injecting drug use (21 studies; 1408 participants), treatment completion was 97·5% (95% CI 96·6-98·3) and SVR was 87·7% (95% CI 84·2-91·3). Among individuals receiving opioid substitution therapy (36 studies; 2987 participants), treatment completion was 97·4% (95% CI 96·5-98·3) and SVR was 90·7% (95% CI 88·5-93·0). Among individuals with recent injecting drug use (eight studies; 670 participants), treatment completion was 96·9% (95% CI 95·6-98·2) and SVR was 87·4% (95% CI 82·0-92·8). In meta-regression analysis, clinical trials (vs observational studies; adjusted odd ratio 2·18, 95% CI 1·27-3·75; p=0·006) and higher mean or median age (1·07, 1·02-1·12; p=0·008) were significantly associated with higher SVR. Clinical trials (0·45, 0·22-0·94; p=0·033) and older age (0·94, 0·88-0·99; p=0·034) were also significantly associated with a lower proportion of participants lost to follow-up.
Response to DAA therapy was favourable among people with recent drug use (including those who inject) and those receiving opioid substitution therapy, supporting broadening access in these populations.
The Kirby Institute, UNSW Sydney, and National Health and Medical Research Council of Australia.
The burden of hepatitis C virus (HCV) infection is escalating among people who inject drugs (PWID), yet testing and treatment remains suboptimal. The aim of this systematic review was to evaluate the ...effectiveness of interventions to enhance HCV testing, linkage to care, and treatment uptake among PWID.
A systematic literature search of Medline (Ovid 1946 – present), Embase, Global Health, Cochrane Central Register of Controlled Trials, PsycINFO, Clinical Trials Registry, and Web of Science was conducted covering interventional studies published before 20 July 2016. Studies evaluating interventions to enhance HCV testing, linkage to care or treatment among PWID were included. Data from included studies was extracted by one reviewer and checked by a second reviewer with disagreements discussed until consensus was reached. Relative risk ratios and corresponding confidence intervals were generated for studies included in analysis.
After adjusting for duplicates, 10,116 records were identified. A total of 14 studies were included for analysis, of which 57% were randomised controlled trials. Interventions to enhance HCV testing included on-site testing with pre-test counselling and education; and dried blood spot testing. Interventions to enhance linkage to care included facilitated referral for HCV assessment and scheduling of specialist appointments for clients. Interventions to enhance HCV treatment uptake included integrated HCV care, drug use and psychiatric services delivered by a multidisciplinary team with case management services, with or without non-invasive liver disease assessment. All studies were conducted in the interferon treatment era and there were no studies conducted in low- and middle-income countries.
In the direct acting antiviral treatment era, well-designed studies evaluating interventions to enhance a simplified care cascade are crucial in facilitating treatment scale-up.
Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake ...is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.
There is increasing evidence that elimination strategies have resulted in better outcomes for public health, the economy, and civil liberties than have mitigation strategies throughout the first year ...of the COVID-19 pandemic. With vaccines that offer high protection against severe forms of COVID-19, and increasing vaccination coverage, policy makers have had to reassess the trade-offs between different options. The desirability and feasibility of eliminating SARS-CoV-2 compared with other strategies should also be re-evaluated from the perspective of different fields, including epidemiology, public health, and economics. To end the pandemic as soon as possible—be it through elimination or reaching an acceptable endemic level—several key topics have emerged centring around coordination, both locally and internationally, and vaccine distribution. Without coordination it is difficult if not impossible to sustain elimination, which is particularly relevant in highly connected regions, such as Europe. Regarding vaccination, concerns remain with respect to equitable distribution, and the risk of the emergence of new variants of concern. Looking forward, it is crucial to overcome the dichotomy between elimination and mitigation, and to jointly define a long-term objective that can accommodate different political and societal realities.
Aims
The 2016 Global Health Sector Strategy (GHSS) on viral hepatitis aims to reduce new hepatitis C virus (HCV) infections by 80% by 2030, including a 30% reduction by 2020. This study aimed to ...estimate primary HCV incident infection among a national sample of people who inject drugs (PWID) before and after the introduction of unrestricted access to HCV direct‐acting antiviral (DAA) therapy via Australia's Pharmaceutical Benefits Scheme in 2016.
Design
A simple deterministic linkage method identified repeat respondents in serial cross‐sectional surveys conducted among PWID. Two separate retrospective cohorts of HCV antibody‐negative respondents were created, corresponding to the pre‐ (2010–15) and post‐ (2016–21) DAA time‐periods.
Setting and Participants
This study took place in Australia. Among 757 PWID retained (376 pre‐DAA, 381 post‐DAA), more than half were male (60%), the majority were heterosexual (80%), the median age was 40 years (interquartile range = 33–46 years) and the predominant drugs last injected were heroin (24%), pharmaceutical opioids (27%) and methamphetamine (41%).
Measurements
The primary outcome was HCV seroconversion, defined as a negative HCV antibody test result followed by a positive HCV antibody result. Time to primary incident HCV infection was estimated using the person‐years (PY) method.
Findings
A total 97 of 376 (2010–15) and 41 of 381 (2016–21) HCV seroconversions were identified. Primary HCV incidence more than halved, from 13.6 per 100 PY 95% confidence intervals (CI) = 11.2, 16.6 in 2010–15 to 5.4 per 100 PY (95% CI = 3.9, 7.3) in 2016–21. The decline was independent of observed differences in demographic and drug use characteristics over the two time‐periods (adjusted hazard ratio = 0.47, 95% CI = 0.31–0.69, P < 0.001).
Conclusions
Australia has had a 53% reduction in primary hepatitis C virus (HCV) incidence among people who inject drugs following unrestricted availability of HCV direct acting antiviral therapy in March 2016. Given that PWID are the predominant population at risk of HCV infection in Australia, findings add to the evidence that Australia has probably met its 2020 Global Health Sector Strategy subtarget of a 30% decline in new infections.
Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those ...that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.
The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists ...regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
Background. Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this ...review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID. Methods. A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection. Results. Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 45% were PWID), pooled SVR was 56% (95% confidence interval CI, 50%–61%) for all genotypes, 37% (95% CI, 26%–48%) for genotypes 1/4, and 67% (95% CI, 56%–78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%–89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%–27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9–6.1) per 100 person-years. Conclusions. HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.
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