Stephen Corson

Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

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.

Modelling the prevalence of HCV amongst people who inject drugs : an investigation into the risks associated with injecting paraphernalia sharing

BACKGROUND In order to prevent the spread of the hepatitis C virus (HCV) amongst people who inject drugs (PWID), it is imperative that any injecting risk behaviour which may contribute to the transmission of disease has its role quantified. To inform public health organisations, mathematical modelling techniques were used to explore the risk of HCV infection through the sharing of injecting paraphernalia (including filters, cookers and water). METHODS A mathematical model was developed for the spread of HCV based on the injecting behaviour of PWID in Scotland, with transmission occurring through the sharing of needles/syringes and other injecting paraphernalia. Numerical simulations were used to estimate the transmission probability for HCV through the sharing of injecting paraphernalia such that the modelled endemic HCV prevalence fitted with that observed amongst PWID in Scotland. RESULTS The transmission probability of HCV through injecting paraphernalia was modelled to be over 8 times lower than that through needles/syringes (approximately 0.19-0.30% and 2.5%, respectively), assuming transmission occurs through a combination of at least filters and cookers. In the context of reported needle/syringe and paraphernalia sharing rates in Scotland, it is estimated that 38% and 62% of HCV infections are contributed by these practices, respectively. If needle/syringe sharing rates were to be twice those reported, the contributions would be 70% and 30%, respectively. CONCLUSION Given that the sharing of injecting paraphernalia among PWID is common, HCV transmission through this route could be contributing to the growing healthcare burden associated with this chronic disease. Every effort should therefore be made to establish (a) the contribution that paraphernalia sharing is making to the spread of HCV, and (b) the effectiveness of services providing sterile paraphernalia in preventing infection.

Mathematically modelling the spread of hepatitis C in injecting drug users.

Mathematical modelling can provide valuable insights into the biological and epidemiological properties of infectious diseases as well as the potential impact of intervention strategies employed by health organizations worldwide. In this paper, we develop a deterministic, compartmental mathematical model to approximate the spread of the hepatitis C virus (HCV) in an injecting drug user (IDU) population. Using analytical techniques, we find that the model behaviour is determined by the basic reproductive number R(0), where R(0) = 1 is a critical threshold separating two different outcomes. If R(0) ≤ 1 and HCV is initially present in the population, we find that the system will reach a disease-free equilibrium where HCV has been eliminated in all IDUs and needles. If R(0) > 1, then there is a unique positive endemic equilibrium which we show is locally stable. We then use simulations to verify our analytical results and examine the effect of different parameter values and intervention measures on HCV prevalence estimates.

Risk of Hepatitis C virus re-infection following spontaneous viral clearance in injecting drug users: A systematic review

BACKGROUND In order to develop new ways to prevent Hepatitis C virus (HCV) transmission amongst injecting drug users (IDUs), it is necessary to fully understand the dynamics of this disease. We reviewed the evidence on three key areas of HCV transmission in this population: the rate of acute HCV infection amongst IDUs who have spontaneously resolved a previous infection, the rate of chronic HCV infection amongst IDUs who have spontaneously resolved a previous infection, and the ability of IDUs to be re-infected with either the same or a different HCV genotype. METHODS A literature search of PUBMED (January 1950 to January 2009), EMBASE (January 1980 to January 2009) and PsycINFO (January 1967 to January 2009) for English language, primary research papers was undertaken to identify longitudinal studies examining HCV re-infection following spontaneous viral clearance amongst IDUs. RESULTS The systematic review identified three studies that satisfied the inclusion and exclusion criteria. Regarding the risk of acute HCV infection amongst IDUs, the findings from the three studies were conflicting and thus provided no compelling evidence in support of an increased or decreased risk of acute infection amongst IDUs who have spontaneously resolved compared to those previously uninfected. Limited evidence was found from two studies to support a reduced risk of subsequent chronic HCV infection in those who have previously spontaneously resolved an infection. Further, two studies found IDUs who spontaneously resolved an infection can be re-infected (with comparable proportions) with either the same or a different HCV genotype. CONCLUSION The limited, and sometimes contradictory, evidence published in the worldwide literature highlights the need for more longitudinal studies of IDUs to fully understand the dynamics of the disease in this population.

A time since onset of injection model for hepatitis C spread amongst injecting drug users

Studies of hepatitis C virus (HCV) infection amongst injecting drug users (IDUs) have suggested that this population can be separated into two risk groups (naive and experienced) with different injecting risk behaviours. Understanding the differences between these two groups and how they interact could lead to a better allocation of prevention measures designed to reduce the burden of HCV in this population. In this paper we develop a deterministic, compartmental mathematical model for the spread of HCV in an IDU population that has been separated into two groups (naive and experienced) by time since onset of injection. We will first describe the model. After deriving the system of governing equations, we will examine the basic reproductive number

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Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

, the existence and uniqueness of equilibrium solutions and the global stability of the disease free equilibrium (DFE) solution. The model behaviour is determined by the basic reproductive number, with