PhD Student, University of New South Wales
Understanding how hepatitis C virus is transmitted is vital to being able to eliminate this disease.
By harnessing the power of phylogenetics, we can gain a better understanding of how, when and by whom infectious diseases like hepatitis C virus (HCV) are being transmitted. Because viruses like HCV evolve a little bit every time they are transmitted from one person to another, by studying the evolutionary patterns in the virus's DNA using phylogenetic techniques, we can retrace the pathway the virus took as it spread through a population. By combining phylogenetics techniques with traditional clinical epidemiology, I have been studying the transmission of recently acquired hepatitis C virus in Australia.
Little is known about hepatitis C virus (HCV) transmission among people with recent infection and in particular among gay and bisexual men with HIV co-infection. Data and specimens from five studies of recent HCV in Australia recruited between 2005 and 2015 were used for this study. Viral RNA was extracted from samples and HCV Core-E2 region sequenced. Phylogenetic trees were inferred using maximum likelihood analysis in RAxML and 1000 bootstrap replicates performed. Clusters were identified using ClusterPicker (90% bootstrap threshold, 5% genetic distance [GD] threshold). Multivariate logistic regression analysis was performed in STATA (version 14.1).
In total, 352 participants were eligible for inclusion in this study. HCV Core-E2 sequences were obtained from 274 participants, and among HIV/HCV co-infected participants, 35% (48/138) were in a pair or cluster, compared to 21% (29/136, p=0.013) of participants with HCV mono-infection. Acquiring HCV sexually, as opposed to intravenous drug use, was independently associated with being in a pair or cluster.
The greater proportion of clustering found among HIV/HCV co-infected participants and independent association between clustering and acquiring HCV infection sexually, highlights the importance of sexual networks among people with HIV infection in transmission of HCV. This study demonstrates the urgent need to provide broad treatment access and enhance treatment uptake, together with ongoing monitoring of the phylogeny, to eliminate HCV transmission among people with HIV infection in Australia. As HCV/HIV co-infection is associated with accelerated disease progression, strategies to reduce HCV transmission are very important in this population.
Abstract: The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk - such as people who inject drugs (PWID) - irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID.There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential 'prevention benefit' of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and 'prevention benefit' hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures.Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.
Pub.: 03 Nov '15, Pinned: 13 Jun '17
Abstract: New direct-acting antivirals (DAAs) are highly effective for hepatitis C virus (HCV) treatment. However, their prices have been widely debated. Decision-analytic models can project the long-term value of HCV treatment. Therefore, understanding of the methods used in these models and how they could influence results is important.Our objective was to describe and systematically review the methodological approaches in published cost-effectiveness models of chronic HCV treatment with DAAs.We searched several electronic databases, including Medline, Embase and EconLit, from 2011 to 2015.Study selection was performed by two reviewers independently. We included any cost-effectiveness analysis comparing DAAs with the old standard of care for HCV treatment. We excluded non-English-language studies and studies not reporting quality-adjusted life-years.One reviewer collected data and assessed the quality of reporting, using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Another reviewer crosschecked the abstracted information. The development methods of the included studies were synthetized on the basis of good modelling practice recommendations.Review of 304 citations revealed 36 cost-effectiveness analyses. The reporting quality scores of most articles were rated as acceptable, between 67 and 100 %. The majority of the studies were conducted in Europe (50 %), followed by the USA (44 %). Fifty-six percent of the 36 studies evaluated the cost effectiveness of HCV treatment in both treatment-naive and treatment-experienced patients, 97 % included genotype 1 patients and 53 % evaluated the cost effectiveness of second-generation or oral DAAs in comparison with the previous standard of care or other DAAs. Twenty-one models defined health states in terms of METAVIR fibrosis scores. Only one study used a discrete-event simulation approach, and the remainder used state-transition models. The time horizons varied; however, 89 % of studies used a lifetime horizon. One study was conducted from a societal perspective. Thirty-three percent of studies did not conduct any model validation. We also noted that none of the studies modelled HCV treatment as a prevention strategy, 86 % of models did not consider the possibility of re-infection with HCV after successful treatment, 97 % of studies did not consider indirect economic benefits resulting from HCV treatment and none of the studies evaluating oral DAAs used real-world data.The search was limited by date (from 1 January 2011 to 8 September 2015) and was also limited to English-language and published reports.Most modelling studies used a similar modelling structure and could have underestimated the value of HCV treatment. Future modelling efforts should consider the benefits of HCV treatment in preventing transmission, extra-hepatic and indirect economic benefits of HCV treatment, real-world cost-effectiveness analysis and cost effectiveness of HCV treatment in low- and middle-income countries.
Pub.: 11 Jan '16, Pinned: 13 Jun '17
Abstract: We report on the hepatitis C virus (HCV) epidemic among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in the United Kingdom and model its trajectory with or without scaled-up HCV direct-acting antivirals (DAAs).A dynamic HCV transmission model among HIV-diagnosed MSM in the United Kingdom was calibrated to HCV prevalence (antibody [Ab] or RNA positive), incidence, and treatment from 2004 to 2011 among HIV-diagnosed MSM in the UK Collaborative HIV Cohort (UK CHIC). The epidemic was projected with current or scaled-up HCV treatment, with or without a 20% behavioral risk reduction.HCV prevalence among HIV-positive MSM in UK CHIC increased from 7.3% in 2004 to 9.9% in 2011, whereas primary incidence was flat (1.02-1.38 per 100 person-years). Over the next decade, modeling suggests 94% of infections are attributable to high-risk individuals, comprising 7% of the population. Without treatment, HCV chronic prevalence could have been 38% higher in 2015 (11.9% vs 8.6%). With current treatment and sustained virological response rates (status quo), chronic prevalence is likely to increase to 11% by 2025, but stabilize with DAA introduction in 2015. With DAA scale-up to 80% within 1 year of diagnosis (regardless of disease stage), and 20% per year thereafter, chronic prevalence could decline by 71% (to 3.2%) compared to status quo in 2025. With additional behavioral interventions, chronic prevalence could decline further to <2.5% by 2025.Epidemiological data and modeling suggest a continuing HCV epidemic among HIV-diagnosed MSM in the United Kingdom driven by high-risk individuals, despite high treatment rates. Substantial reductions in HCV transmission could be achieved through scale-up of DAAs and moderately effective behavioral interventions.
Pub.: 26 Feb '16, Pinned: 13 Jun '17
Abstract: Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. HCV predominates in people who inject drugs; a group in whom anti‐viral therapy has previously been withheld on the basis of chaotic lifestyles and associated risks of reinfection. New research has emerged which suggests that by specifically targeting HCV‐infected people who inject drugs for treatment, the pool of HCV would deplete, thus reducing overall transmission and eventually leading to HCV eradication.To outline the requirements for HCV eradication and review the evidence that this is achievable.Expert review of the literature.The achievement of HCV eradication using ‘treatment as prevention’ is supported by numerous epidemiological modelling studies employing a variety of models in several contexts including people who inject drugs, men who have sex with men and prisoners. More recent studies also incorporate the newer, more efficacious direct‐acting anti‐viral drugs. These drugs have been shown to be safe and effective in people who inject drugs in clinical trials. There is no empirical evidence of the impact of treatment as prevention strategies on population prevalence.This review highlights the efforts to control HCV and evaluates the possibilities of achieving eradication of HCV. Currently, the technologies required to achieve HCV eradication exist, but the infrastructure to deliver them is not generally available or of insufficient scale outside of specific areas. Such areas are yet to demonstrate that elimination is possible, but results of studies in these areas are awaited. Such a demonstration would be proof of principle for eradication. Although we are aspiring towards HCV eradication, elimination is the more realistic prospect.
Pub.: 20 May '16, Pinned: 13 Jun '17
Abstract: Because problematic patterns of alcohol and other substance use are prevalent drivers of the HIV/AIDS epidemic, comprehensive interventions are needed for substance-using men who have sex with men (SUMSM). We conducted a systematic review of 12 randomized controlled trials (RCTs) of behavioral interventions for reducing condomless anal intercourse (CAI) in SUMSM. Three RCTs observed that cognitive-behavioral or motivational interviewing interventions achieved a 24% to 40% decrease in CAI. Interventions also tended to demonstrate greater efficacy for reducing CAI and substance use among those who had lower severity of substance use disorder symptoms. Although behavioral interventions for SUMSM are one potentially important component of bio-behavioral HIV/AIDS prevention, further research is needed to examine if integrative approaches that cultivate resilience and target co-occurring syndemic conditions demonstrate greater efficacy. Multi-level intervention approaches are also needed to optimize the effectiveness of pre-exposure prophylaxis and HIV treatment as prevention with SUMSM.
Pub.: 04 Jun '16, Pinned: 13 Jun '17
Abstract: Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP) and opiate substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID.We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual-level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1-2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012.This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.
Pub.: 12 Aug '14, Pinned: 13 Jun '17
Abstract: Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.
Pub.: 14 Nov '13, Pinned: 13 Jun '17
Abstract: The hepatitis C virus (HCV) epidemic is a major health issue; in most developed countries it is driven by people who inject drugs (PWID). Injecting networks powerfully influence HCV transmission. In this paper we provide an overview of 10 years of research into injecting networks and HCV, culminating in a network-based approach to provision of direct-acting antiviral therapy.Between 2005 and 2010 we followed a cohort of 413 PWID, measuring HCV incidence, prevalence and injecting risk, including network-related factors. We developed an individual-based HCV transmission model, using it to simulate the spread of HCV through the empirical social network of PWID. In addition, we created an empirically grounded network model of injecting relationships using exponential random graph models (ERGMs), allowing simulation of realistic networks for investigating HCV treatment and intervention strategies. Our empirical work and modelling underpins the TAP Study, which is examining the feasibility of community-based treatment of PWID with DAAs.We observed incidence rates of HCV primary infection and reinfection of 12.8 per 100 person-years (PY) (95%CI: 7.7-20.0) and 28.8 per 100 PY (95%CI: 15.0-55.4), respectively, and determined that HCV transmission clusters correlated with reported injecting relationships. Transmission modelling showed that the empirical network provided some protective effect, slowing HCV transmission compared to a fully connected, homogenous PWID population. Our ERGMs revealed that treating PWID and all their contacts was the most effective strategy and targeting treatment to infected PWID with the most contacts the least effective.Networks-based approaches greatly increase understanding of HCV transmission and will inform the implementation of treatment as prevention using DAAs.
Pub.: 15 Jun '15, Pinned: 13 Jun '17
Abstract: Hepatitis C virus (HCV) elimination is now an achievable goal;1–3 the WHO is likely to set ambitious but achievable 2030 elimination targets later this year.4 In high-income countries, people who inject drugs (PWID) are the group at greatest risk of HCV infection,5–7 with HCV prevalence among PWID varying from 10% to 97% in different regions of the globe.7 8 In low income and middle income countries, HCV transmission can be due to iatrogenic transmission (in the formal and informal health systems), injecting drug use or a combination of the two.9 Highly effective direct-acting antiviral (DAA) treatment with improved tolerability is the cornerstone of HCV elimination. Models that combine HCV treatment as prevention and harm reduction services—including opioid substitution therapy (OST) and needle and syringe programmes (NSPs)—suggest that HCV prevalence...
Pub.: 10 Nov '16, Pinned: 13 Jun '17
Abstract: HCV transmission remains high in people who inject drugs (PWID) in Montréal. New direct-acting antivirals (DAAs), highly effective and more tolerable than previous regimens, make a "Treatment as Prevention" (TasP) strategy more feasible. This study assesses how improvements in the cascade of care could impact hepatitis C burden among PWID in Montréal.We used a dynamic model to simulate HCV incidence and prevalence after 10 years, and cirrhosis complications after 10 and 40 years. Eight scenarios of improved cascade of care were examined.Using a baseline incidence and prevalence of 22.1/100 person-years (PY) and 53.1%, implementing the current cascade of care using DAAs would lead to HCV incidence and prevalence estimates at 10 years of 9.4/100PY and 55.8%, respectively. Increasing the treatment initiation rate from 5%/year initially to 20%/year resulted in large decreases in incidence (6.4/100PY), prevalence (36.6%), and cirrhosis complications (-18%/-37% after 10/40 years). When restricting treatment to fibrosis level ≥ F2 instead of F0 (reference scenario), such decreases in HCV occurrence were unreachable. Improving the whole cascade of care led to the greatest effect by halving both the incidence and prevalence at 10 years, and the number of cirrhosis complications after 40 years.The current level of treatment access in Montréal is limiting a massive decrease in hepatitis C burden among PWID. A substantial treatment scale-up, regardless of fibrosis level, is necessary. While improving the rest of the cascade of care is necessary to optimize a TasP strategy and control the HCV epidemic, a treatment scale-up is first needed.
Pub.: 23 Feb '17, Pinned: 13 Jun '17
Abstract: Sexual transmission of Hepatitis C virus (HCV) in men who have sex with men (MSM) and its interaction with HIV status, sexually transmitted infections and sexual behaviour is poorly understood. We assessed the incidence and predictors of HCV infection in HIV positive MSM.The electronic medical record and laboratory results from HIV positive MSM in care at a large urban public specialist HIV clinic embedded in a sexual health centre in Melbourne Australia were collected. Patients with two or more HCV antibody tests between January 2008 and March 2016 and with no record of injecting drug use were included. The HCV exposure intervals were the periods between a negative HCV test and the next HCV test. We compared HCV exposure intervals temporally associated with and without newly acquired syphilis or anorectal chlamydia. HCV exposure intervals were also categorised as being before or after HIV virological suppression and by most recent and nadir CD4 cell count.Thirty seven new HCV infections were diagnosed in 822 HIV positive MSM with no history of injecting drug use over 3114 person years (PY) of follow-up. Mean age was 43.1 years (±12.5) and mean CD4 cell count nadir was 362 cells/uL (±186). The incidence of HCV infection in the study population was 1.19/100PY (0.99-1.38). The incidence in exposure periods temporally close to new syphilis infection was 4.72/100PY (3.35-6.08) and to new anorectal chlamydia infection was 1.37/100PY (0.81-1.93). The incidence in men without supressed viral load was 3.19/100PY (1.89-4.49). In the multivariate Cox regression analysis only younger age (aHR 0.67 (0.48-0.92)), exposure periods temporally associated to new syphilis infection (aHR 4.96 (2.46-9.99)) and higher CD4 cell count nadir (aHR 1.26 per 100 cells/uL (1.01-1.58)) were associated with increased risk of HCV infection. During the study period the incidence of syphilis increased dramatically but the incidence of HCV infection remained the same.Incidence of HCV infection is associated with syphilis but not anorectal chlamydia which suggests a biological rather than behavioural risk modification. Rising syphilis incidence may offset declines in HCV transmission through HCV treatment as prevention.
Pub.: 04 Mar '17, Pinned: 13 Jun '17
Abstract: Treatment as Prevention (TasP) using directly-acting antivirals has been advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but treatment is expensive and TasP's effectiveness is uncertain. Previous modelling has assumed a homogeneously-mixed population or a static network lacking turnover in the population and injecting partnerships. We developed a transmission-dynamic model on a dynamic network of injecting partnerships using data from survey of injecting behaviour carried out in London, UK. We studied transmission on a novel exponential-clustered network, as well as on two simpler networks for comparison, an exponential unclustered and a random network, and found that TasP's effectiveness differs markedly. With respect to an exponential-clustered network, the random network (and homogeneously-mixed population) overestimate TasP's effectiveness, whereas the exponential-unclustered network underestimates it. For all network types TasP's effectiveness depends on whether treated patients change risk behaviour, and on treatment coverage: higher coverage requires fewer total treatments for the same health gain. Whilst TasP can greatly reduce HCV prevalence, incidence of infection, and incidence of reinfection in PWID, assessment of TasP's effectiveness needs to take account of the injecting-partnership network structure and post-treatment behaviour change, and further empirical study is required.
Pub.: 14 May '17, Pinned: 13 Jun '17
Abstract: Hepatitis C virus (HCV) infection is endemic among people who inject drugs (PWID) globally. Despite high prevalence, treatment uptake is low, with cumulative uptake <10% in most settings. This study aimed to populate the cascade of HCV testing, care and treatment among PWID using data collected in Australia prior to the introduction of broadly accessible interferon-free direct-acting antiviral (DAA) therapies in March 2016.The Australian Needle and Syringe Program Survey is a cross-sectional surveillance system that recruits ∼2300 PWID annually and collects behavioural data and dried blood samples (DBS). HCV antibody and ribonucleic acid (RNA) test results from DBS collected in 2015 were combined with data on HCV diagnostic testing, care and treatment to populate the HCV cascade among Australian PWID.Among an estimated 93,000 PWID in Australia in 2015, the majority (89%) had a lifetime history of HCV antibody testing. More than half (57%) of PWID tested HCV antibody positive and of these, 79% had detectable HCV RNA consistent with active infection. Less than half (46%) of HCV antibody positive PWID had received confirmatory HCV RNA testing. Among the estimated 43,201 PWID with active infection or chronic infection that had been successfully treated, 31% had received specialist HCV assessment, 8% had received antiviral treatment and 3% were cured.This study provides baseline estimates of the cascade of HCV testing, care and treatment among PWID through enhancement of a well-established surveillance mechanism. Characterisation of the HCV cascade among PWID will be crucial to evaluating and monitoring the roll out of direct-acting antiviral therapies in Australia, including assessing potential HCV treatment as prevention benefits.
Pub.: 06 Jun '17, Pinned: 13 Jun '17
Abstract: Sexual contact is thought to be an inefficient mode of hepatitis C virus (HCV) transmission. However, reports of sexually transmitted HCV infection among HIV-infected men who have sex with men (MSM) began to appear in 2004. The patients were of early middle age with well-controlled HIV infection, participated in unprotected receptive sex, and frequently used noninjection recreational drugs. Molecular studies showed evidence of clusters of transmission between patients in different countries in Europe. Spontaneous clearance was relatively rare, but treatment with pegylated interferon and ribavirin resulted in cure in about two thirds of patients. Of concern was the finding of moderately advanced fibrosis during the early stages of HCV infection. HIV-infected MSM are a new risk group for HCV infection and so should be screened regularly for HCV infection.
Pub.: 11 Feb '11, Pinned: 13 Jun '17
Abstract: High rates of hepatitis C virus (HCV) transmission are found in samples of people who inject drugs (PWID) throughout the world. The objective of this paper was to meta-analyze the effects of risk-reduction interventions on HCV seroconversion and identify the most effective intervention types.We performed a systematic review and meta-analysis of published and unpublished studies. Eligible studies reported on the association between participation in interventions intended to reduce unsafe drug injection and HCV seroconversion in samples of PWID.The meta-analysis included 26 eligible studies of behavioral interventions, substance-use treatment, syringe access, syringe disinfection, and multicomponent interventions. Interventions using multiple combined strategies reduced risk of seroconversion by 75% (pooled relative risk, .25; 95% confidence interval, .07-.83). Effects of single-method interventions ranged from .6 to 1.6.Interventions using strategies that combined substance-use treatment and support for safe injection were most effective at reducing HCV seroconversion. Determining the effective dose and combination of interventions for specific subgroups of PWID is a research priority. However, our meta-analysis shows that HCV infection can be prevented in PWID.
Pub.: 02 Jun '11, Pinned: 13 Jun '17
Abstract: To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs).Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness.Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment.A total of 2986 IDUs surveyed during 2001-09.Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys.Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST (I2=48%, P=0.09) and NSP (I2=0%, P=0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs)=0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR=0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: -27.3 to -14.4).There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population.
Pub.: 28 May '11, Pinned: 13 Jun '17
Abstract: The risk-related behaviours and practices associated with injection drug use remain a driver of HIV and hepatitis C virus (HCV) transmission throughout the world. Here we evaluated HIV and HCV transmission patterns in the context of social networks of injection drug users (IDU) recruited from a higher incidence region in order to better understand factors that contribute to ongoing transmission among IDU.IDU recruited through a chain-referral method provided biological specimens for analysis. HIV and HCV positive specimens were sequenced and analyzed using phylogenetic methods (Neighbour-joining and bayesian) and transmission patterns of HIV and HCV evaluated in the context of the recruitment networks.Among the 407 recruited IDU, HCV and HIV prevalence were 60.6% and 10.1%, respectively; 98% of HIV positive individuals were co-infected with HCV. Thirty-six percent of HCV sequences were associated with clusters, compared to 67% of HIV sequences. Four (16.7%) of the 24 HCV clusters contained membership separated by 2 or fewer recruitment cycles, compared to 10 (41.6%) derived from more than one recruitment component. Two (28.6%) of the 7 HIV clusters contained membership separated by 2 or fewer recruitment cycles while 6 (85.7%) were composed of inter component membership.Few HIV and HCV transmissions coincided with the recruitment networks, suggesting that they occurred in a different social context or a context not captured by the recruitment network. However, among the complete cohort, a higher degree of HIV clustering indicates many are recent infections originating from within current social networks, whereas a larger proportion of HCV infections may have occurred earlier in injecting history and in the context of a different social environment.
Pub.: 30 Jul '11, Pinned: 13 Jun '17
Abstract: Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-α + ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of £ 521 and £ 2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of £ 6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/non-IDUs are halved.Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted.
Pub.: 08 Sep '11, Pinned: 13 Jun '17
Abstract: To investigate the impact of scaling-up opiate substitution therapy (OST) and high coverage needle and syringe programmes (100%NSP-obtaining more sterile syringes than you inject) on HCV prevalence among injecting drug users (IDUs).Hepatitis C virus HCV transmission modelling using U.K. estimates for effect of OST and 100%NSP on individual risk of HCV infection.Range of chronic HCV prevalent (20/40/60%) settings with no OST/100%NSP, and U.K. setting with 50% coverage of both OST and 100%NSP.Injecting drug users.Decrease in HCV prevalence after 5-20 years due to scale-up of OST and 100%NSP to 20/40/60% coverage in no OST/100%NSP settings, or from 50% to 60/70/80% coverage in the U.K. setting.For 40% chronic HCV prevalence, scaling-up OST and 100%NSP from 0% to 20% coverage reduces HCV prevalence by 13% after 10 years. This increases to a 24/33% relative reduction at 40/60% coverage. Marginally less impact occurs in higher prevalence settings over 10 years, but this becomes more pronounced over time. In the United Kingdom, without current coverage levels of OST and 100%NSP the chronic HCV prevalence could be 65% instead of 40%. However, increasing OST and 100%NSP coverage further is unlikely to reduce chronic prevalence to less than 30% over 10 years unless coverage becomes ≥80%.Scaling-up opiate substitution therapy and high coverage needle and syringe programmes can reduce hepatitis C prevalence among injecting drug users, but reductions can be modest and require long-term sustained intervention coverage. In high coverage settings, other interventions are needed to further decrease hepatitis C prevalence. In low coverage settings, sustained scale-up of both interventions is needed.
Pub.: 09 May '12, Pinned: 13 Jun '17
Abstract: Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)-infected and -uninfected men who have sex with men (MSM) over the entire HIV epidemic has not been comprehensively conducted.To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)-negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984-2011 for anti-HCV seroconversion.During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio [IRR], 1.40/10 years, P < .001), enrollment in the later (2001-2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm(3) increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm(3), whereas there was no association with highly active antiretroviral therapy.The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4(+) T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.
Pub.: 28 Mar '13, Pinned: 13 Jun '17
Abstract: Nosocomial transmission events still play an important role in hepatitis C virus (HCV) spreading. Among most reported medical procedures involved in nosocomial transmission, endoscopy procedures remain controversial and might be underestimated.The aim of the study was to investigate a case of nosocomial person-to-person transmission of HCV in an endoscopy unit.An acute HCV infection was detected in a person that had undergone a colonoscopy after an HCV-infected patient. Serum samples from both persons were subjected to a molecular epidemiology study. The HCV NS5B genetic region was amplified and directly sequenced and the E1-E2 region was amplified, cloned and sequenced (20 clones per specimen). All sequences were subjected to phylogenetic analyses. A conventional epidemiological investigation was performed to determine the most likely cause of HCV transmission.NS5B sequence analysis revealed that both persons were infected with closely related HCV-1b strains. Furthermore, phylogenetic analysis of E1-E2 sequences evidenced a direct transmission between patients. The epidemiological investigation pointed out to anesthetic procedures as the most likely source of HCV transmission. The index case, not having spontaneously cleared the infection 10 months after infection, required antiviral treatment, which resulted in a sustained virological response.The molecular epidemiology study performed provided evidence of a person-to-person transmission of HCV during a colonoscopy procedure, and the anesthetic procedure was the most likely source of HCV transmission. This study highlights the importance of strictly following standard precautions by healthcare workers in order to prevent nosocomial HCV transmission.
Pub.: 10 Apr '13, Pinned: 13 Jun '17
Abstract: Injecting drug users (IDUs) are a major and most important risk factor for rising hepatitis C virus (HCV) prevalence in Iran.The objective of this study was to determine the effectiveness of methadone maintenance treatment (MMT) in prevention of HCV infection transmission among IDUs.A mathematical modeling has been used to estimate number of HCV infections averted. The input parameters used in the model were collected by self-reported method from 259 IDUs before registering and one year after MMT. Nonparametric statistical tests have been used to compare risky injecting and sexual behaviors among IDUs before and after participating in MMT program. Deterministic sensitivity analyses were done to show the effects of parameters' uncertainty on outcome.Of the 259 participants, 98.4% (255) were men, the mean age ± SD was 33.1 ± 7.58 years and HCV prevalence was 50%. The studied IDUs reported lower rate of risky injecting and sexual behavior after participation in MMT program. The cumulative incidence of HCV per 100 IDUs due to sharing injection and unsafe sexual contact with MMT program were 13.84 (95% CI: 6.17 -21.51), 0.0003 (0.0001 - 0.0005) and without it 36.48 (25.84 - 47.11) and 0.0004 (0.0002-0.0006) respectively.The MMT program is an effective intervention to prevent HCV infection transmission, although it is essential to compare its effectiveness with other interventions before implementing it in nationwide.
Pub.: 27 Sep '13, Pinned: 13 Jun '17
Abstract: Identification and vaccination of adults at risk for hepatitis B virus acquisition through sexual contact is a key strategy to reduce new hepatitis B virus infections among at-risk adults. Hepatitis C has emerged as a sexually transmitted infection among men with male sex partners (MSM). Several biological and behavioral factors have been linked to hepatitis C virus transmission among MSM, including human immunodeficiency virus coinfection; participation in sexual practices that result in mucosal damage or result in exposure to blood; presence of sexually transmitted diseases (STIs), particularly ulcerative STIs; multiple/casual sex partners; and unprotected anal intercourse.
Pub.: 28 Nov '13, Pinned: 13 Jun '17
Abstract: To document the relationships between injecting drug use, imprisonment and hepatitis C virus (HCV) infection.Prospective cohort study.Multiple prisons in New South Wales, Australia.HCV seronegative prisoners with a life-time history of injecting drug use (IDU) were enrolled and followed prospectively (n = 210) by interview and HCV antibody and RNA testing 6-12-monthly for up to 4 years when in prison.HCV incidence was calculated using the person-years method. Cox regression was used to identify predictors of incident infection using time-dependent covariates.Almost half the cohort reported IDU during follow-up (103 subjects; 49.1%) and 65 (31%) also reported sharing of the injecting apparatus. There were 38 HCV incident cases in 269.94 person-years (py) of follow-up with an estimated incidence of 14.08 per 100 py [confidence interval (CI) = 9.96-19.32]. Incident infection was associated independently with Indigenous background, injecting daily or more and injecting heroin. Three subjects were RNA-positive and antibody-negative at the incident time-point, indicating early infection, which provided a second incidence estimate of 9.4%. Analysis of continuously incarcerated subjects (n = 114) followed over 126.73 py, identified 13 new HCV infections (10.26 per 100 py, CI = 5.46-17.54), one of which was an early infection case. Bleach-cleansing of injecting equipment and opioid substitution treatment were not associated with a significant reduction in incidence.In New South Wales, Australia, imprisonment is associated with high rates of hepatitis C virus transmission. More effective harm reduction interventions are needed to control HCV in prison settings.
Pub.: 12 Jun '14, Pinned: 13 Jun '17
Abstract: Equipment sharing among people who inject drugs (PWID) is a key risk factor in infection by hepatitis C virus (HCV). Both the effectiveness and cost-effectiveness of interventions aimed at reducing HCV transmission in this population (such as opioid substitution therapy, needle exchange programmes or improved treatment) are difficult to evaluate using field surveys. Ethical issues and complicated access to the PWID population make it difficult to gather epidemiological data. In this context, mathematical modelling of HCV transmission is a useful alternative for comparing the cost and effectiveness of various interventions. Several models have been developed in the past few years. They are often based on strong hypotheses concerning the population structure. This review presents compartmental and individual-based models to underline their strengths and limits in the context of HCV infection among PWID. The final section discusses the main results of the papers.
Pub.: 02 Oct '14, Pinned: 13 Jun '17
Abstract: Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) disease burden and to monitor the impact of prevention and treatment interventions on HCV transmission dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individuals with two or three sequential samples collected <1 year apart. Patristic distances between sequential samples were used to set cutoffs to identify recent transmission clusters. Factors associated with transmission clustering were analyzed using logistic regression. From 618 individuals, 646 sequences were obtained. Depending on the cutoff used, 63 (10%) to 92 (15%) unique individuals were identified within transmission clusters of predicted recent origin. Clustered individuals were more likely to be <40 years old (Adjusted Odds Ratio (AOR) 2.12, 95% CI 1.21-3.73), infected with genotype 1a (AOR 6.60, 95% CI 1.98-41.0), and to be seroconverters with estimated infection duration of <1 year (AOR 3.13, 95% CI 1.29-7.36) or >1 year (AOR 2.19, 95% CI 1.22-3.97).Systematic application of molecular phylogenetics may be used to enhance traditional surveillance methods through identification of recent transmission clusters.
Pub.: 29 Apr '15, Pinned: 13 Jun '17
Abstract: Background: Highly effective direct-acting antiviral (DAA) regimens (90% efficacy) are becoming available for hepatitis C virus (HCV) treatment. This therapeutic revolution leads us to consider possibility of eradicating the virus. However, for this, an effective cascade of care is required. Methods: In the context of the incoming DAAs, we used a dynamic individual-based model including a model of the people who inject drugs (PWID) social network to simulate the impact of improved testing, linkage to care, and adherence to treatment, and of modified treatment recommendation on the transmission and on the morbidity of HCV in PWID in France. Results: Under the current incidence and cascade of care, with treatment initiated at fibrosis stage $\ge$F2, the HCV prevalence decreased from 42.8% to 24.9% [95% confidence interval 24.8%--24.9%] after 10 years. Changing treatment initiation criteria to treat from F0 was the only intervention leading to a substantial additional decrease in the prevalence, which fell to 11.6% [11.6%--11.7%] at 10 years. Combining this change with improved testing, linkage to care, and adherence to treatment decreased HCV prevalence to 7% [7%--7.1%] at 10 years and avoided 15.3% [14.0%-16.6%] and 29.0% [27.9%--30.1%] of cirrhosis complications over 10 and 40 years respectively. Conclusion: A high decrease in viral transmission occurs only when treatment is initiated before liver disease progresses to severe stages, suggesting that systematic treatment in PWID, where incidence remains high, would be beneficial. However, eradication will be difficult to achieve.
Pub.: 08 Jun '15, Pinned: 13 Jun '17
Abstract: The discovery of highly effective hepatitis C virus (HCV) treatments has led to discussion of elimination and intensified interest in models of HCV transmission. In developed settings, HCV disproportionally affects people who inject drugs (PWID), and models are typically used to provide an evidence base for the effectiveness of interventions such as needle and syringe programs, opioid substitution therapy and more recently treating PWID with new generation therapies to achieve specified reductions in prevalence and / or incidence. This manuscript reviews deterministic compartmental S-I, deterministic compartmental S-I-S and network-based transmission models of HCV among PWID. We detail typical assumptions made when modeling injecting risk behavior, virus transmission, treatment and re-infection and how they correspond with available evidence and empirical data.
Pub.: 26 Aug '15, Pinned: 13 Jun '17
Abstract: A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences from public databases. Applying Bayesian inference methods, we reconstructed the global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish sequences mainly formed discrete clusters interspersed between sequences from the rest of the world; the most recent common ancestors of these clusters dated to 1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global diversification and distribution. Extant Scottish sequences originated in Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a strain specificity occurred only in Aberdeen. Specific clusters initially formed separate transmission zones in Glasgow that subsequently overlapped, occasioning city-wide cocirculation. Transmission hot spots were detected with 45% of samples from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was introduced into Scotland in the 1940s, concomitant with its worldwide dispersal likely arising from global-scale historical events. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in HCV dissemination. This fine-scale spatiotemporal reconstruction improves understanding of HCV transmission dynamics in Scotland.HCV is a major health burden and the leading cause of hepatocellular carcinoma. Public health needle exchange and "treatment as prevention" strategies targeting HCV are designed to reduce prevalence of the virus in people who inject drugs (PWID), potentially mitigating the future burden of HCV-associated liver disease. Understanding HCV transmission dynamics could increase the effectiveness of such public health initiatives by identifying and targeting regions playing a central role in virus dispersal. In this study, we examined HCV transmission in Scotland by analyzing the genetic relatedness of strains from PWID alongside data inferring the year individuals became infected and residential information at a geographically finer-scale resolution than in previous studies. Clusters of Scotland-specific strains were identified with regional specificity, and mapping the spread of HCV allowed the identification of key areas central to HCV transmission in Scotland. This research provides a basis for identifying HCV transmission hot spots.
Pub.: 28 Aug '15, Pinned: 13 Jun '17