Dataset Information

Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs?

ABSTRACT:

Background

Widely access to interferon-free direct-acting antiviral regimens (IFN-free DAA) is poised to dramatically change the impact of the HCV epidemic among people who inject drugs (PWID). We evaluated the long-term effect of increasing HCV testing, treatment and engagement into harm-reduction activities, focused on active PWID, on the HCV epidemic in British Columbia (BC), Canada.

Methods

We built a compartmental model of HCV disease transmission stratified by disease progression, transmission risk, and fibrosis level. We explored the effect of: (1) Increasing treatment rates from 8 to 20, 40 and 80 per 1000 infected PWID/year; (2) Increasing treatment eligibility based on fibrosis level; (3) Maximizing the effect of testing by performing it immediately upon ending the acute phase; (4) Increasing access to harm-reduction activities to reduce the risk of re-infection; (5) Different HCV antiviral regimens on the Control Reproduction Number Rc. We assessed the impact of these interventions on incidence, prevalence and mortality from 2016 to 2030.

Results

Of all HCV antiviral regimens, only IFN-free DAAs offered a high chance of disease elimination (i.e. Rc < 1), but it would be necessary to substantially increase the current low testing and treatment rates. Assuming a treatment rate of 80 per 1000 infected PWID per year, coupled with a high testing rate, the incidence rate, at the end of 2030, could decrease from 92.9 per 1000 susceptible PWID per year (Status Quo) to 82.8 (by treating only PWID with fibrosis level F2 and higher) or to 65.5 (by treating PWID regardless of fibrosis level). If PWID also had access to increased harm-reduction activities, the incidence rate further decreased to 53.1 per 1000 susceptible PWID per year. We also obtained significant decreases in prevalence and mortality at the end of 2030.

Conclusions

The combination of increased access to HCV testing, highly efficacious antiviral treatment and harm-reduction programs can substantially decrease the burden of the HCV epidemic among PWID. However, unless we increase the current levels of treatment and testing, the HCV epidemic among PWID in BC, and in other parts of the world with similar epidemiological background, will remain a substantial public health concern for many years.

SUBMITTER: Lima VD

PROVIDER: S-EPMC4669174 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs?

Lima Viviane D VD Rozada Ignacio I Grebely Jason J Hull Mark M Lourenco Lillian L Nosyk Bohdan B Krajden Mel M Yoshida Eric E Wood Evan E Montaner Julio S G JS

PloS one 20151203 12

<h4>Background</h4>Widely access to interferon-free direct-acting antiviral regimens (IFN-free DAA) is poised to dramatically change the impact of the HCV epidemic among people who inject drugs (PWID). We evaluated the long-term effect of increasing HCV testing, treatment and engagement into harm-reduction activities, focused on active PWID, on the HCV epidemic in British Columbia (BC), Canada.<h4>Methods</h4>We built a compartmental model of HCV disease transmission stratified by disease progre ...[more]

PMID: 26633652

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Project description:Background & aimsScale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing.MethodsThrough linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test.ResultsOf 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected.ConclusionsHCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly.Lay summaryIncreased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

Project description:Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Project description:Background and aimsThe advent of highly effective hepatitis C (HCV) treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID). However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment.MethodsDynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years), moderate (70% protection for 10 years) or high (90% protection for 20 years) efficacy vaccine. Sensitivities to various parameters were examined.ResultsTo halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years) of 162 (72%), 77 (56%) and 44 (38%) per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only) and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine's impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year.ConclusionsAchievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important intervention option.

Project description:IntroductionAlmost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs.MethodsWe conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1. Patients with HCV genotype 1 (GT1) and GT4 received ledipasvir (90 mg) plus sofosbuvir (400 mg), those with HCV GT2 received sofosbuvir plus weight-based ribavirin, and those with HCV GT3 received daclatasvir (60 mg) plus sofosbuvir. Treatment was continued for 12 weeks in all patients. The primary endpoints were rate of sustained virologic response at 12 weeks after end of therapy (SVR12) and occurrence of adverse events during DAA therapy.ResultsEighteen (67%) patients had had received interferon-based therapy, and 11 (41%) had compensated cirrhosis. HCV genotypes were GT1a 4 (15%), GT1b 16 (59%), GT1 undetermined 2 (7%), GT2a 1 (4%), GT3a 3 (11%) and GT4a 1 (4%). All patients were on combination antiretroviral therapy (cART) and had undetectable HIV-1 viral load (<20 copies/μL) at baseline. All patients achieved SVR12. Serious adverse events were observed in 3 patients: arteritis of the leg, which resolved after completion of DAA therapy, asymptomatic QT prolongation and gastrointestinal hemorrhage. cART failure was noted in one patient due to emergence of raltegravir resistance during ledipasvir/sofosbuvir treatment. Although α-fetoprotein, Mac-2 binding protein glycosylation isomer (M2BPGi), and Fibro Scan (FS) scores decreased in most patients during DAA therapy, M2BPGi (>2.0 cutoff index) and FS scores (>15.0 kPa) were still high in 6 patients at week 36.ConclusionsDAA therapy is effective in all patients. However, adverse events and efficacy of cART should be monitored closely.

Dataset Information

Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs?

Background

Methods

Results

Conclusions

Publications

Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs?

Similar Datasets

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