Publications by authors named "Gregory J Dore"

346 Publications

Opportunities to enhance linkage to hepatitis C care among hospitalised people with recent drug dependence in New South Wales, Australia: A population-based linkage study.

Clin Infect Dis 2021 Jun 9. Epub 2021 Jun 9.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalisation, yet admissions are not utilised for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalised while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalisation in the DAA era.

Methods: We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalisation.

Results: Among 57,467 people, 14,938 (26%) had evidence of recent drug dependence, 50% (n=7,506) of whom were hospitalised while DAA eligible. Incidence of selected cause-specific hospitalisation was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100PY), and injection-related infectious disease (9.15 per 100PY) hospitalisations, and lowest for alcohol use disorder (4.58 per 100PY) and liver-related (3.13 per 100PY). 65% (n=4,898) of those hospitalised had been admitted >2 times and 46% (n=3,437) were hospitalised >7 days. By the end of 2018, DAA therapy was lowest for those hospitalised >2 times, for >7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications.

Conclusions: Among people who have evidence of recent drug dependence, frequent hospitalisation-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.
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http://dx.doi.org/10.1093/cid/ciab526DOI Listing
June 2021

Evaluating the prevention benefit of HCV treatment: Modelling the SToP-C treatment as prevention study in prisons.

Hepatology 2021 Jun 9. Epub 2021 Jun 9.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background & Aims: Between 2014-2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear due to the study not having a control group. We used modelling to consider this question.

Approach & Results: We parameterised and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was due to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI] 41.9-54.1%) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%, 95% confidence interval 23.4-64.2%) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95%UI -0.3-13.6%). This suggests 85.1% (95%UI 72.6-100.6%) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95%UI -0.6-27.4%).

Conclusions: Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.
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http://dx.doi.org/10.1002/hep.32002DOI Listing
June 2021

Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection.

J Hepatol 2021 May 20. Epub 2021 May 20.

St Vincent's Hospital, Sydney, Australia.

Background And Aims: Shortened duration therapy for acute and recent hepatitis C virus (HCV) infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens, however large randomised studies are lacking.

Methods: REACT was an NIH-funded multicentre international, open-label, randomised, phase 4 non-inferiority trial examining the efficacy of short course (6 weeks) versus standard course (12 weeks) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection <= 12 months). Randomisation occurred at week 6. The primary endpoint was SVR12 in the intention-to treat (ITT) population. A total of 250 participants were planned for enrolment. On advice of the data safety and monitoring board the study was halted early.

Results: Primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n=93), standard arm (n=95). Ninety seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI: -18.6, 1.0). By modified ITT analysis in which non-virological reasons for failure were excluded (death, reinfection, lost to follow-up) SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p=0.025).

Conclusions: In this randomised study in recent HCV infection, 6 weeks sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12 weeks duration.

Lay Summary: In this randomised trial one hundred and eighty people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were nine cases of relapse after treatment in the short course and two using the standard course. A shortened course of 6 weeks therapy for hepatitis C infection was considered not as effective as a standard twelve week course in people with recently acquired hepatitis C infection.

Trial Registration: Clinicaltrials.gov Identifier: NCT02625909.
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http://dx.doi.org/10.1016/j.jhep.2021.04.056DOI Listing
May 2021

Evaluation of hepatitis C treatment-as-prevention within Australian prisons (SToP-C): a prospective cohort study.

Lancet Gastroenterol Hepatol 2021 Jul 7;6(7):533-546. Epub 2021 May 7.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address:

Background: Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting.

Methods: SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two maximum-security prisons (male) and two medium-security prisons (one male, one female) in New South Wales, Australia. All prison inmates aged at least 18 years were eligible for enrolment. After HCV testing, participants were monitored for risk behaviours and HCV infection, among three sub-populations: uninfected (HCV antibody-negative); previously infected (HCV antibody-positive, HCV RNA-negative); and infected (HCV antibody and HCV RNA-positive). Uninfected participants were followed up every 3-6 months to detect HCV primary infection and previously infected participants were followed up every 3-6 months to detect re-infection. Participants with HCV infection were assessed for treatment, initially standard-of-care treatment (administered by prison health services) from 2014 to mid-2017, then direct-acting antiviral (DAA) treatment scale-up from mid-2017 onwards (12 weeks of sofosbuvir plus velpatasvir, administered through SToP-C). Participants were followed up until study closure in November, 2019. The primary study outcome was HCV incidence before and after DAA treatment scale-up among participants at risk of HCV primary infection or re-infection. This study is registered with ClinicalTrials.gov, NCT02064049.

Findings: Between Oct 30, 2014, and Sept 30, 2019, 3691 participants were enrolled in the SToP-C study. 719 (19%) participants had detectable HCV RNA, 2240 (61%) were at risk of primary HCV infection, and 725 (20%) were at risk of re-infection at baseline. DAA treatment was initiated in 349 (70%) of 499 eligible participants during the treatment scale-up period. The HCV incidence analysis comprised 1643 participants at risk of HCV infection or re-infection during longitudinal follow-up (median age 33 years [IQR 27-42]; 1350 [82%] male). 487 (30%) of 1643 participants reported injecting drugs in prison. HCV incidence decreased from 8·31 per 100 person-years in the pre-treatment scale-up period to 4·35 per 100 person-years in the post-treatment scale-up period (incidence rate ratio [IRR] 0·52 [95% CI 0·36-0·78]; p=0·0007). The incidence of primary infection decreased from 6·64 per 100 person-years in the pre-treatment scale-up period to 2·85 per 100 person-years in the post-treatment scale-up period (IRR 0·43 [95% CI 0·25-0·74]; p=0·0019), whereas the incidence of re-infection decreased from 12·36 per 100 person-years to 7·27 per 100 person-years (0·59 [0·35-1·00]; p=0·050). Among participants reporting injecting drugs during their current imprisonment, the incidence of primary infection decreased from 39·08 per 100 person-years in the pre-treatment scale-up period to 14·03 per 100 person-years in the post-treatment scale-up period (IRR 0·36 [95% CI 0·16-0·80]; p=0·0091), and the incidence of re-infection decreased from 15·26 per 100 person-years to 9·34 per 100 person-years (0·61 [0·34-1·09]; p=0·093). The adjusted analysis (adjusted for age, Indigenous Australian ethnicity, duration of stay in prison, previous imprisonment, injecting drug use status, and prison site) indicated a significant reduction in the risk of HCV infection between the pre-DAA treatment scale-up and post-DAA treatment scale-up periods (adjusted hazard ratio 0·50 [95% CI 0·33-0·76]; p=0·0014).

Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of a beneficial effect of HCV treatment-as-prevention in this setting. These findings support broad DAA treatment scale-up within incarcerated populations.

Funding: Australian National Health and Medical Research Council Partnership Project Grant and Gilead Sciences.
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http://dx.doi.org/10.1016/S2468-1253(21)00077-7DOI Listing
July 2021

Elimination of hepatitis C in Australia by 2030: a decade and counting.

Authors:
Gregory J Dore

Aust Prescr 2021 Apr 1;44(2):36-37. Epub 2021 Apr 1.

Infectious diseases physician, St Vincent's Hospital, Sydney.

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http://dx.doi.org/10.18773/austprescr.2021.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075743PMC
April 2021

Estimating the number of new hepatitis C infections in Australia in 2015, prior to the scale-up of direct-acting antiviral treatment.

J Gastroenterol Hepatol 2021 Mar 10. Epub 2021 Mar 10.

Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia.

Background And Aim: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years.

Methods: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015.

Results: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015.

Conclusions: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.
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http://dx.doi.org/10.1111/jgh.15485DOI Listing
March 2021

Hepatitis C virus cure before hepatocellular carcinoma diagnosis is associated with improved survival.

J Viral Hepat 2021 May 2;28(5):710-718. Epub 2021 Feb 2.

St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.

The impact of hepatitis C virus (HCV) cure on survival in patients with HCV-related hepatocellular carcinoma (HCC) has been examined, although many studies have been subject to survivor treatment selection bias. We assessed the impact of HCV cure before HCC diagnosis on overall survival. Patients with HCV-related HCC at three referral hospitals in Australia were included retrospectively (January 2008 to December 2019). The risk of death following HCC diagnosis among patients who achieved HCV cure before HCC diagnosis was compared to patients who were viraemic at diagnosis. Among 422 patients with HCV-related HCC, 101 (24%) achieved HCV cure before HCC diagnosis, 37 with interferon (IFN) and 64 with direct-acting antiviral (DAA) therapy. Patients with HCV cure were more likely to have no cirrhosis or Child-Pugh A liver disease (83% vs. 66%, p = .002), surveillance detection (71% vs. 48%, p < .001), HCC stage O or A (64% vs. 45%, p < .001) and receive curative initial HCC management (51% vs. 28%, p < .001), compared with patients who were viraemic at diagnosis. The 5-year overall survival was 51% in the HCV cure group and 22% in the viraemic group. In adjusted analysis, risk of death was lower in patients with HCV cure before HCC diagnosis compared with patients who were viraemic at diagnosis (adjusted hazard ratio: 0.63; 95% CI: 0.44-0.91; p = .013). Patients with HCV-related HCC who have achieved HCV cure before HCC diagnosis have improved overall survival compared with patients who were viraemic at diagnosis.
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http://dx.doi.org/10.1111/jvh.13475DOI Listing
May 2021

Identifying the lower age limit for hepatitis C screening in large elimination programmes in highly endemic areas.

Lancet Gastroenterol Hepatol 2021 02;6(2):89-90

Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.

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http://dx.doi.org/10.1016/S2468-1253(20)30371-XDOI Listing
February 2021

Author Correction: Hepatitis C virus elimination: laying the foundation for achieving 2030 targets.

Nat Rev Gastroenterol Hepatol 2021 Feb;18(2):143

Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1038/s41575-020-00407-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095274PMC
February 2021

Hepatitis C virus elimination: laying the foundation for achieving 2030 targets.

Nat Rev Gastroenterol Hepatol 2021 02;18(2):91-92

Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1038/s41575-020-00392-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702726PMC
February 2021

Novel Hepatitic C Virus (HCV) Diagnosis and Treatment Delivery Systems: Facilitating HCV Elimination by Thinking Outside the Clinic.

J Infect Dis 2020 11;222(Suppl 9):S758-S772

The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.
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http://dx.doi.org/10.1093/infdis/jiaa366DOI Listing
November 2020

Prevalence and incidence of hepatitis C virus infection in men who have sex with men: a systematic review and meta-analysis.

Lancet Gastroenterol Hepatol 2021 01 18;6(1):39-56. Epub 2020 Nov 18.

The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

Background: WHO has set targets for hepatitis C virus (HCV) elimination by 2030. We did a global systematic review of HCV prevalence and incidence in men who have sex with men (MSM) to provide updated estimates that can guide community education and public health policy.

Methods: We did a systematic review and meta-analysis of studies published and listed on MEDLINE or Embase between Jan 1, 2000, and Oct 31, 2019, including conference proceedings. Studies were eligible if they reported measures of HCV prevalence or HCV incidence (or both) among MSM. Studies that relied on participants' self-reported HCV status with no laboratory confirmation were excluded. Pooled HCV estimates in MSM were stratified by HIV status and by injecting drug use, then by WHO region and by income level. Random-effects meta-analysis was done to account for between-study heterogeneity and examined using the I statistic. Pooled HCV prevalence was also compared with HCV estimates in the general population and presented as prevalence ratios (PRs). In HIV-negative MSM, incidence estimates were stratified by use of HIV pre-exposure prophylaxis (PrEP). The systematic review was registered with PROSPERO, number CRD42020156262.

Findings: Of 1221 publications identified, 194 were deemed to be eligible and included in the systematic review and meta-analysis. Overall, the pooled HCV prevalence in MSM was 3·4% (95% CI 2·8-4·0; I=98·0%) and was highest in Africa (5·8%, 2·5-10·4) and South-East Asia (5·0%, 0·0-16·6). Globally, HCV prevalence was 1·5% (1·0-2·1) in HIV-negative MSM and 6·3% (5·3-7·5) in HIV-positive MSM. Compared with the general population, HCV prevalence was slightly higher in HIV-negative MSM (PR 1·58, 95% CI 1·14-2·01) and markedly higher (6·22, 5·14-7·29) in HIV-positive MSM. Pooled HCV prevalence was substantially higher in MSM who had ever injected drugs (30·2%, 22·0-39·0) or currently injected drugs (45·6%, 21·6-70·7) than in those who never injected drugs (2·7%, 2·0-3·6). In HIV-negative MSM, the pooled HCV incidence was 0·12 per 1000 person-years (95% CI 0·00-0·72) in individuals not on PrEP and 14·80 per 1000 person-years (9·65-20·95) in individuals on PrEP. HCV incidence in HIV-positive MSM was 8·46 per 1000 person-years (6·78-10·32).

Interpretation: HIV-positive MSM are at substantially increased risk of HCV. Overall, HIV-negative MSM had a slightly higher prevalence of HCV than the general population but had a lower prevalence than HIV-positive MSM. High HCV incidence in more recent PrEP studies suggests that as PrEP use increases, greater HCV transmission might occur. HCV burden in MSM varies considerably by region, which is likely to be associated with variation in the prevalence of injecting drug use and HIV.

Funding: World Health Organization.
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http://dx.doi.org/10.1016/S2468-1253(20)30303-4DOI Listing
January 2021

Creating an environment for equitable access to direct-acting antiviral therapy for people who inject drugs with hepatitis C.

Liver Int 2020 10;40(10):2353-2355

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

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http://dx.doi.org/10.1111/liv.14661DOI Listing
October 2020

Hepatocellular carcinoma risk with antivirals for chronic hepatitis B: no longer confounding.

Lancet Gastroenterol Hepatol 2020 12 30;5(12):1028-1029. Epub 2020 Sep 30.

Department of Infectious Diseases, Kirby Institute, UNSW Sydney, Sydney, NSW 2052, Australia; St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.

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http://dx.doi.org/10.1016/S2468-1253(20)30270-3DOI Listing
December 2020

The role of social capital in facilitating hepatitis C treatment scale-up within a treatment-as-prevention trial in the male prison setting.

Addiction 2021 05 18;116(5):1162-1171. Epub 2020 Oct 18.

Centre for Social Research in Health, UNSW Sydney, Sydney, NSW, Australia.

Background And Aims: Hepatitis C (HCV) is a global public health concern, particularly in the prison setting where prevalence is substantially higher than in the general population. Direct-acting antivirals have changed the treatment landscape, allowing for treatment scale-up efforts potentially sufficient to achieve prevention of onward transmission (treatment-as-prevention). The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study was the first trial to examine the efficacy of HCV treatment-as-prevention in the prison setting. Social capital is a social resource which has been found to influence health outcomes. This qualitative study sought to understand the role of social capital within an HCV treatment-as-prevention trial in the prison setting.

Design: Semi-structured in-depth interviews were undertaken with participants recruited from the SToP-C study following HCV treatment completion (with cure).

Setting: Three male correctional centres in New South Wales, Australia (including two maximum-security and one minimum-security).

Participants: Twenty-three men in prison participated in semi-structured interviews.

Measurements: Thematic analysis of transcripts was completed using a social capital framework, which enabled exploration of the ways in which bonding, bridging and linking social capital promoted or inhibited HCV treatment uptake within a treatment-as-prevention trial.

Findings: Social capital fostered HCV treatment uptake within an HCV treatment-as-prevention trial in the prison setting. Bonding social capital encouraged treatment uptake and alleviated concerns of side effects, bridging social capital supported prison-wide treatment uptake, and linking social capital fostered trust in study personnel (including nurses and correctional officers), thereby enhancing treatment engagement.

Conclusions: Social capital, including bonding, bridging and linking, can play an important role in hepatitis C treatment-as-prevention efforts within the male prison setting.
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http://dx.doi.org/10.1111/add.15277DOI Listing
May 2021

High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia.

J Hepatol 2021 Feb 12;74(2):293-302. Epub 2020 Sep 12.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background & Aims: High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence.

Methods: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence.

Results: 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24-2.36), recent incarceration (aOR 1.10; 95% CI 1.01-1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13-1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72-0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69-0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78-0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82-0.98), HBV coinfection (aOR 0.69; 95% CI 0.59-0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84-0.98).

Conclusions: These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination.

Lay Summary: To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.
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http://dx.doi.org/10.1016/j.jhep.2020.08.038DOI Listing
February 2021

Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for HCV NS5A-inhibitor experienced patients with difficult to cure characteristics.

Clin Infect Dis 2020 Sep 5. Epub 2020 Sep 5.

Victorian Infectious Diseases Reference Laboratory, Victoria, Australia.

Background: In clinical trials, HCV salvage treatment with Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort.

Methods: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE).

Findings: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n=46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n=82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n=18/18, GT1b n=2/4), 89% in GT3 (n=59/66) and 100% in GT6 (n=3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were four serious AEs including one death and three hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12.

Conclusion: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most however serious AEs can occur in those with advanced liver disease.
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http://dx.doi.org/10.1093/cid/ciaa1318DOI Listing
September 2020

Concomitant Marked Decline in Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Other Respiratory Viruses Among Symptomatic Patients Following Public Health Interventions in Australia: Data from St Vincent's Hospital and Associated Screening Clinics, Sydney, NSW.

Clin Infect Dis 2021 05;72(10):e649-e651

Department of Infectious Diseases, St Vincent's Hospital, Sydney, Australia.

Our Australian hospital tested almost 22 000 symptomatic people over 11 weeks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multiplex polymerase chain reaction (PCR) assay. Following travel bans and physical distancing, SARS-CoV-2 and other respiratory viruses diagnoses fell dramatically. Increasing rhinovirus diagnoses as social control measures were relaxed may indirectly indicate an elevated risk of coronavirus disease 2019 (COVID-19) resurgence.
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http://dx.doi.org/10.1093/cid/ciaa1256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499558PMC
May 2021

Coordination, cooperation, and creativity within harm reduction networks in Iran: COVID-19 prevention and control among people who use drugs.

Int J Drug Policy 2020 Aug 17:102908. Epub 2020 Aug 17.

Rebirth Charity Society, Tehran, Iran.

An unprecedented public health crisis confronts the world. Iran is among the hardest-hit countries, where effects of the COVID-19 pandemic are stretched across society and felt by the most marginalised people. Among people who use drugs, a comprehensive response to the crisis calls for broad collaboration, coordination, and creativity involving multiple government and non-government organisations. This commentary provides early insights into an unfolding experience, demonstrating the operational and policy impact of an initiative, bringing together a diverse array of harm reduction stakeholders to address the pandemic. In the context of lived experiences of social and economic marginalization, this initiative intends to lead efforts in developing an equitable response to the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.drugpo.2020.102908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430297PMC
August 2020

People with Hepatitis C Who Inject Drugs - Underserved, Not Undeserving.

N Engl J Med 2020 Aug;383(7):608-611

From the Kirby Institute, UNSW Sydney, and St. Vincent's Hospital - both in Sydney (G.J.D.); and Philadelphia FIGHT Community Health Centers and the Perelman School of Medicine, University of Pennsylvania - both in Philadelphia (S.T.).

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http://dx.doi.org/10.1056/NEJMp2002126DOI Listing
August 2020

Evaluation of the Aptima HCV Quant Dx Assay for Hepatitis C Virus RNA Detection from Fingerstick Capillary Dried Blood Spot and Venepuncture-Collected Samples.

J Infect Dis 2021 Mar;223(5):818-826

Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

Background: Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations.

Methods: We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard).

Results: One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%-35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2 = 0.96).

Conclusions: The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility.
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http://dx.doi.org/10.1093/infdis/jiaa442DOI Listing
March 2021

Estimating the Consensus hepatitis C Cascade of Care among people who inject drugs in Australia: Pre and post availability of direct acting antiviral therapy.

Int J Drug Policy 2020 09 6;83:102837. Epub 2020 Jul 6.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background Monitoring the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is an essential component of the response to World Health Organisation's (WHO) hepatitis elimination goals. This study aimed to estimate the Consensus hepatitis C CoC among PWID using data collected in Australia prior to and after the introduction of unrestricted direct-acting antiviral (DAA) therapy in March 2016. Methods The Australian Needle Syringe Program Survey is a cross-sectional bio-behavioural surveillance system that recruits >2000 PWID annually. Using data from 2015 and 2019, HCV antibody and ribonucleic acid (RNA) test results from dried blood spots were combined with self-reported data on HCV diagnostic testing and treatment to project HCV Consensus CoC indicators at a population-level among Australian PWID. Results Among an estimated 75,000 people who inject drugs on a regular basis in Australia, the number with active HCV infection declined from 32,619 (44%) in October 2015 to 12,679 (17%) in October 2019. The majority (78% in 2015 and 2019) of PWID reported HCV diagnosis, while the proportion of those diagnosed who were treated increased from 3% in 2015 to 47% in 2019. Among those treated, the proportion who were HCV RNA negative and assumed to have been successfully treated (cured), increased from 27% in 2015 to 88% in 2019. Conclusion This study demonstrates remarkable HCV CoC progress among PWID in Australia following availability of DAA therapy. There was a substantial increase in the proportion of HCV diagnosed PWID who initiated treatment and were cured, while the number of PWID with active HCV infection more than halved over a 3.5 year period. Estimates of the Consensus hepatitis C CoC among PWID is required to monitor progress toward WHO HCV elimination goals.
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http://dx.doi.org/10.1016/j.drugpo.2020.102837DOI Listing
September 2020

Estimating the Consensus hepatitis C Cascade of Care among people who inject drugs in Australia: Pre and post availability of direct acting antiviral therapy.

Int J Drug Policy 2020 09 6;83:102837. Epub 2020 Jul 6.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background Monitoring the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is an essential component of the response to World Health Organisation's (WHO) hepatitis elimination goals. This study aimed to estimate the Consensus hepatitis C CoC among PWID using data collected in Australia prior to and after the introduction of unrestricted direct-acting antiviral (DAA) therapy in March 2016. Methods The Australian Needle Syringe Program Survey is a cross-sectional bio-behavioural surveillance system that recruits >2000 PWID annually. Using data from 2015 and 2019, HCV antibody and ribonucleic acid (RNA) test results from dried blood spots were combined with self-reported data on HCV diagnostic testing and treatment to project HCV Consensus CoC indicators at a population-level among Australian PWID. Results Among an estimated 75,000 people who inject drugs on a regular basis in Australia, the number with active HCV infection declined from 32,619 (44%) in October 2015 to 12,679 (17%) in October 2019. The majority (78% in 2015 and 2019) of PWID reported HCV diagnosis, while the proportion of those diagnosed who were treated increased from 3% in 2015 to 47% in 2019. Among those treated, the proportion who were HCV RNA negative and assumed to have been successfully treated (cured), increased from 27% in 2015 to 88% in 2019. Conclusion This study demonstrates remarkable HCV CoC progress among PWID in Australia following availability of DAA therapy. There was a substantial increase in the proportion of HCV diagnosed PWID who initiated treatment and were cured, while the number of PWID with active HCV infection more than halved over a 3.5 year period. Estimates of the Consensus hepatitis C CoC among PWID is required to monitor progress toward WHO HCV elimination goals.
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http://dx.doi.org/10.1016/j.drugpo.2020.102837DOI Listing
September 2020

Impact of an Open Access Nationwide Treatment Model on Hepatitis C Virus Antiviral Drug Resistance.

Hepatol Commun 2020 Jun 6;4(6):904-915. Epub 2020 Apr 6.

Storr Liver Centre The Westmead Institute for Medical Research The University of Sydney and Westmead Hospital Sydney Australia.

Direct acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment, but drug resistance could undermine proposed global elimination targets. Real-world studies are needed to inform the impact of widespread DAA treatment on antiviral resistance in the community. The prevalence and range of posttreatment resistance-associated substitutions (RASs) was determined in Australian patients with open access to DAAs through a wide range of prescribers. NS3, NS5A, and NS5B regions were amplified by polymerase chain reaction and analyzed by population sequencing. Clinically relevant RASs were identified using online databases (ReCALL and Geno2Pheno[hcv]). Of 572 samples, 60% were from genotype 3 and 27% from genotype 1a. Ninety-two percent of people failed a DAA regimen containing an NS5A inhibitor, including 10% with a pangenotype regimen. NS5A RASs were detected in 72% of people with genotype 1 and 80% with genotype 3. For genotype 1, there was a range of RASs across the NS5A region, while for genotype 3, the Y93H RAS predominated (72%). The prevalence of NS3 RASs was higher in people exposed to an NS3 inhibitor (35% vs. 3.9%;  < 0.0001). NS5B resistance was rare, with a single case of sofosbuvir resistance. Multiclass drug resistance was found in 33% of people exposed to both NS3 and NS5A inhibitors. : The high prevalence of NS5A RASs among people failing DAA therapy reinforces the importance of specific retreatment regimens, ideally guided by resistance testing. The impact of multiclass drug resistance on retreatment in people exposed to both NS3 and NS5A inhibitors needs to be assessed in real-world studies. Surveillance for increasing antiviral resistance during treatment scale-up is essential to maintain the efficacy of current DAA regimens.
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http://dx.doi.org/10.1002/hep4.1496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262285PMC
June 2020

Association between opioid agonist therapy and testing, treatment uptake, and treatment outcomes for hepatitis C infection among people who inject drugs: A systematic review and meta-analysis.

Clin Infect Dis 2020 May 24. Epub 2020 May 24.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background: People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID.

Methods: Bibliographic databases and conference presentations were searched for studies assessing the association between OAT and HCV testing, treatment, and treatment outcomes [direct-acting antiviral (DAA) therapy only] among people who inject drugs (in the past year). Meta-analysis was used to pool estimates.

Results: Among 9,877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in one study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing [4 studies; odds ratio (OR), 1.80; 95% CI:1.36, 2.39), HCV RNA testing among those who were HCV antibody positive (2 studies; OR, 1.83; 95% CI:1.27, 2.62), and DAA treatment uptake among those who were HCV RNA positive (7 studies; OR 1.53; 95% CI: 1.07, 2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies).

Conclusions: Opioid agonist therapy can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts.
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http://dx.doi.org/10.1093/cid/ciaa612DOI Listing
May 2020

Progress towards elimination of hepatitis C infection among people who inject drugs in Australia: The ETHOS Engage Study.

Clin Infect Dis 2020 May 18. Epub 2020 May 18.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background & Aims: Evaluating progress towards HCV elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia.

Methods: ETHOS Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSP). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick).

Results: Between May 2018-September 2019, 1,443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio: 1.47; 95%CI: 1.00, 2.16), incarcerated in previous year (2.04; 1.38, 3.02), and those injecting drugs ≥daily (2.26; 1.43, 2.42). Among those with previous chronic or current HCV, 66% (n=520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (0.68; 0.48, 0.95), participants who were homeless (0.59; 0.38, 0.96), and those injecting ≥daily (0.51; 0.31, 0.89). People aged ≥45 (1.46; 1.06, 2.01) and people receiving OAT (2.62; 1.52, 4.51) were more likely to report HCV treatment.

Conclusions: Unrestricted DAA access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalisation may require additional support and tailored strategies to enhance treatment.
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http://dx.doi.org/10.1093/cid/ciaa571DOI Listing
May 2020

Progress Toward Hepatitis C Virus Elimination: Therapy and Implementation.

Gastroenterol Clin North Am 2020 06 29;49(2):253-277. Epub 2020 Mar 29.

Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Sydney, Sydney, Australia.

The World Health Organization has called for the elimination of hepatitis C virus (HCV) as a public health threat by 2030. Highly effective direct-acting antiviral agents provide the therapeutic tools required for elimination. In the absence of a vaccine, HCV elimination will require enhanced primary prevention and an increase in the proportions of people diagnosed and treated. Given that globally only 20% of people with chronic HCV are diagnosed, and around 5% have initiated HCV treatment, the task ahead is enormous. But, global public health needs optimism, and countries currently on track for HCV elimination provide a pathway forward.
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http://dx.doi.org/10.1016/j.gtc.2020.01.005DOI Listing
June 2020

Universal screening for hepatitis C virus infection should be linked to universal treatment access.

Nat Rev Gastroenterol Hepatol 2020 06;17(6):321-322

The Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1038/s41575-020-0306-8DOI Listing
June 2020

Hepatitis C elimination in Australia: progress and challenges.

Med J Aust 2020 05 19;212(8):362-363. Epub 2020 Apr 19.

Kirby Institute, UNSW, Sydney, NSW.

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http://dx.doi.org/10.5694/mja2.50584DOI Listing
May 2020