Publications by authors named "Behzad Hajarizadeh"

89 Publications

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

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

Impact of Shave Biopsy on Diagnosis and Management of Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

Ann Surg Oncol 2021 Mar 29. Epub 2021 Mar 29.

Auckland Regional Plastic, Reconstructive and Hand Surgery Unit, Middlemore Hospital, Auckland, New Zealand.

Background: Melanoma is the most lethal skin cancer. Excision biopsy is generally recommended for clinically suspicious pigmented lesions; however, a proportion of cutaneous melanomas are diagnosed by shave biopsy. A systematic review was undertaken to investigate the impact of shave biopsy on tumor staging, treatment recommendations, and prognosis.

Methodology: The MEDLINE, Embase, and Cochrane Library databases were searched for relevant articles. Data on deep margin status on shave biopsy, tumor upstaging, and additional treatments on wide local excision (WLE), disease recurrence, and survival effect were analyzed across studies.

Results: Fourteen articles from 2010 to 2020 were included. In total, 3713 patients had melanoma diagnosed on shave biopsy. Meta-analysis revealed a positive deep margin in 42.9% of shave biopsies. Following WLE, change in tumor stage was reported in 7.7% of patients. Additional treatment was recommended for 2.3% of patients in the form of either further WLE and/or sentinel lymph node biopsy. There was high heterogeneity across studies in all outcomes. Four studies reported survival, while no studies found any significant difference in disease-free or overall survival between shave biopsy and other biopsy modalities.

Conclusions: Just over 40% of melanomas diagnosed on shave biopsy report a positive deep margin; however, this translated into a change in tumor stage or treatment recommendations in relatively few patients (7.7% and 2.3%, respectively), with no impact on local recurrence or survival among the studies analyzed.
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http://dx.doi.org/10.1245/s10434-021-09866-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006869PMC
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

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

Addiction 2021 Jul 3;116(7):1664-1676. Epub 2021 Feb 3.

Health Protection Research Unit, Population Health Sciences, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK.

Background And Aim: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID.

Methods: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models.

Results: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95.

Conclusions: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.
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http://dx.doi.org/10.1111/add.15316DOI Listing
July 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

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

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

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

Estimated uptake of hepatitis C direct-acting antiviral treatment among individuals with HIV co-infection in Australia: a retrospective cohort study.

Sex Health 2020 06;17(3):223-230

The Kirby Institute, Wallace Wurth Building, UNSW Sydney, NSW 2051, Australia; and Corresponding author. Email:

Background Unrestricted access to direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has been available in Australia since March 2016. Individuals with HIV-HCV co-infection are at a greater risk of liver fibrosis progression. This study estimated DAA treatment uptake among individuals with HIV-HCV co-infection, during the first year of DAA treatment access in Australia.

Methods: Pharmaceutical Benefits Scheme (PBS) data on dispensed DAA and antiretroviral therapy (ART) prescriptions from March 2016 to March 2017 were used for analysis.

Results: During March 2016 to March 2017, a total of 935 individuals with HIV-HCV co-infection were receiving ART and initiated DAA treatment, with 93% to 97% completing their prescribed course. Estimated DAA treatment uptake in the HIV-HCV-infected population was 41% (935/2290). Most were men (94%). Median age was 50 years. DAA treatment was initiated by specialists in 64% of cases (n = 602), and by general practitioners (GPs) in 25% of cases (n = 238). The proportion of individuals initiated on DAA by GPs increased from 20% in March-April 2016 to 26% in January-March 2017. Most specialists (77%) and GPs (72%) initiated DAA treatment for one to three patients. Among individuals initiated on DAA by GPs, 68% received their ART prescription from the same GP.

Conclusions: A high level of DAA treatment uptake and completion was observed among individuals with HIV-HCV co-infection during the first year of DAA treatment access. The proportion of individuals prescribed DAA by GPs increased over time; this is important for broadened access.
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http://dx.doi.org/10.1071/SH19101DOI Listing
June 2020

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

Clin Infect Dis 2021 04;72(8):1392-1400

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

Background: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT).

Methods: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models.

Results: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection.

Conclusions: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination.

Clinical Trials Registration: NCT02336139 and NCT02498015.
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http://dx.doi.org/10.1093/cid/ciaa253DOI Listing
April 2021

Time to Detection of Hepatitis C Virus Infection With the Xpert HCV Viral Load Fingerstick Point-of-Care Assay: Facilitating a More Rapid Time to Diagnosis.

J Infect Dis 2020 06;221(12):2043-2049

The Kirby Institute, UNSW, Sydney, Australia.

Background: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment.

Methods: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia.

Results: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (n = 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (n = 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level.

Conclusions: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment.
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http://dx.doi.org/10.1093/infdis/jiaa037DOI Listing
June 2020

Systematic review with meta-analysis: effectiveness of direct-acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma.

Aliment Pharmacol Ther 2020 01 6;51(1):34-52. Epub 2019 Dec 6.

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

Background: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making.

Aim: To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.

Methods: Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates.

Results: Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1-90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0-91.4) and 92.4% (95% CI 91.1-93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43-0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3-92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3-99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1-95.6).

Conclusion: Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.
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http://dx.doi.org/10.1111/apt.15598DOI Listing
January 2020

Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis.

J Hepatol 2020 04 27;72(4):643-657. Epub 2019 Nov 27.

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

Background & Aims: HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT).

Methods: We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.

Results: Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates.

Conclusion: HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.

Lay Summary: Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
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http://dx.doi.org/10.1016/j.jhep.2019.11.012DOI Listing
April 2020

Hepatitis C virus testing, liver disease assessment and treatment uptake among people who inject drugs pre- and post-universal access to direct-acting antiviral treatment in Australia: The LiveRLife study.

J Viral Hepat 2020 03 6;27(3):281-293. Epub 2019 Dec 6.

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

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct-acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole-blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre-DAA era to 38% in the DAA era. Significant liver fibrosis (F2-F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18-7.04) and attending a clinical follow-up with nurse (aOR, 3.19; 95% CI, 1.61-6.32) or physician (aOR, 11.83; 95% CI, 4.89-28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.
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http://dx.doi.org/10.1111/jvh.13233DOI Listing
March 2020

Adherence to Once-daily and Twice-daily Direct-acting Antiviral Therapy for Hepatitis C Infection Among People With Recent Injection Drug Use or Current Opioid Agonist Therapy.

Clin Infect Dis 2020 10;71(7):e115-e124

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

Background: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy.

Methods: SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns.

Results: Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897).

Conclusions: This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.
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http://dx.doi.org/10.1093/cid/ciz1089DOI Listing
October 2020

Drug use and risk behaviour profile, and the prevalence of HIV, hepatitis C and hepatitis B among people with methamphetamine use in Iran.

Int J Drug Policy 2019 11 22;73:129-134. Epub 2019 Oct 22.

Iranian Center for Communicable Diseases Control, Ministry of Health & Medical Education, Tehran, Iran. Electronic address:

Background: Stimulants substances use, particularly methamphetamine use, is increasing globally, including in Iran. This study assessed the drug use and risk behaviour profile, and prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among a large population using methamphetamine as their primary drug in Iran.

Methods: This cross-sectional study was conducted in eight provinces of Iran. Individuals using methamphetamine for ≥3 months during the past three years, with no life-time history of injecting opioid drugs were enrolled. Drug use and risk behaviour data were collected through interviews. Blood samples were tested for HIV antibodies (HIV Ab), HCV antibodies (HCV Ab), and HBV surface antigen (HBs Ag).

Result: Among 567 participated, 84% were men and mean age was 36 years. Smoking with pipe was the most common method of methamphetamine use (53%), while 13% had a history of injecting methamphetamine, among whom 30% shared needles or syringes. Among those having sex during intoxication phase (n = 270), 48% never used condom. The prevalence of HIV Ab, HCV Ab and HBs Ag was 6.7% (95%CI: 4.7-9.1), 19.4% (95%CI: 16.2-22.9) and 1.4% (95%CI: 0.6-2.7), respectively. Age ≥ 30 years (adjusted OR [aOR]: 2.10, 95%CI: 1.18-3.76), lower education (high school vs. tertiary education, aOR: 13.95, 95%CI: 1.90-102.60), and injecting methamphetamine (aOR: 1.92, 95%CI 1.10-3.35) were significantly associated with HCV exposure. No factor was found associated with HIV infection. Among those reporting no potential injecting or sexual risk factors, 19.8% and 6.8% have HCV Ab positive and HIV Ab positive, respectively.

Conclusion: High prevalence of injecting and sexual risk behaviours, HIV infection and HCV exposure were found among individuals using methamphetamine as their primary drug, demonstrating them as an emerging population at risk of HIV and HCV in Iran. Targeted screening and harm reduction programs for this population are required.
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http://dx.doi.org/10.1016/j.drugpo.2019.09.018DOI Listing
November 2019

Evaluation of a hepatitis C virus core antigen assay from venepuncture and dried blood spot collected samples: A cohort study.

J Viral Hepat 2019 12 18;26(12):1423-1430. Epub 2019 Sep 18.

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

The global scale-up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two-drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6-36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90-100) and 100% (95% CI: 93-100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80-97) and 92.5% (95% CI: 82-98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97-100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture.
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http://dx.doi.org/10.1111/jvh.13196DOI Listing
December 2019

Elimination of hepatitis C virus infection among people who use drugs: Ensuring equitable access to prevention, treatment, and care for all.

Int J Drug Policy 2019 10 23;72:1-10. Epub 2019 Jul 23.

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

There have been major strides towards the World Health Organization goal to eliminate hepatitis C virus (HCV) infection as a global public health threat. The availability of simple, well-tolerated direct-acting antiviral therapies for HCV infection that can achieve a cure in >95% of people has provided an important tool to help achieve the global elimination targets. Encouragingly, therapy is highly effective among people receiving opioid agonist therapy and people who have recently injected drugs. Moving forward, major challenges include ensuring that new infections are prevented from occurring and that people who are living with HCV are tested, linked to care, treated, receive appropriate follow-up, and have equitable access to care. This editorial highlights key themes and articles in a special issue focusing on the elimination of HCV among people who inject drugs. An overarching consideration flowing from this work is how to ensure equitable access to HCV treatment and care for all. This special issue maps the field in relation to: HCV prevention; the cascade of HCV care; strategies to enhance testing, linkage to care, and treatment uptake; and HCV treatment and reinfection. In addition, papers draw attention to the 'risk environments' and socio-ecological determinants of HCV acquisition, barriers to HCV care, the importance of messaging around the side-effects of new direct-acting antiviral therapies, the positive transformative potential of treatment and cure, and the key role of community-based drug user organizations in the HCV response. While this special issue highlights some successful efforts towards HCV elimination among people who inject drugs, it also highlights the relative lack of attention to settings in which resources enabling elimination are scarce, and where elimination hopes and potentials are less clear, such as in many low and middle income countries. Strengthening capacity in areas of the world where resources are more limited will be a critical step towards ensuring equity for all so that global HCV elimination among PWID can be achieved.
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http://dx.doi.org/10.1016/j.drugpo.2019.07.016DOI Listing
October 2019

An intervention to improve HCV testing, linkage to care, and treatment among people who use drugs in Tehran, Iran: The ENHANCE study.

Int J Drug Policy 2019 10 11;72:99-105. Epub 2019 Jul 11.

Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Globally, HCV testing, linkage to care and treatment is sub-optimal among people who use drugs (PWUD). This study aimed to evaluate the impact of an innovative intervention to enhance HCV testing, linkage to care, and treatment initiation among PWUD in Tehran, Iran.

Methods: ENHANCE is a non-randomized trial evaluating the effect of on-site rapid HCV antibody testing, venepuncture for HCV RNA testing (HCV antibody positive only), liver fibrosis assessment, and linkage to care to enhance direct-acting antiviral (DAA) therapy (sofosbuvir/daclatasvir) initiation for HCV among people with a history of drug use. Recruitment was from April 2018 and will continue to July 2019, through three opioid substitution treatment (OST) clinics, five community-based drop-in centres, and one homeless reception centre. Participants initiated DAA therapy at a specialist clinic (OST clinics) or on-site (other sites), with monitoring provided on-site or at the specialist clinic (for those with cirrhosis attending OST clinics).

Results: Among 632 participants enrolled (median age, 44 years), 97% were male, 28% had a history of injecting drug use, and 58% had used drugs within the previous year. HCV antibody prevalence was 27%; 62% and 15% among those with and without a history of injecting drug use. Among 170 HCV antibody positive participants, 168 had HCV RNA testing (99%), of whom 134 (80%) were positive. Among HCV RNA positive participants, treatment initiation was 84%: 100% (45/45), 96% (46/48) and 54% (22/41) in OST clinics, drop-in centres, and homeless reception settings, respectively.

Conclusion: Following on-site HCV testing and linkage to care, HCV treatment uptake was extremely high among PWUD, apart from the homeless reception population. This intervention could be explored in other settings globally to enhance HCV scale-up and elimination efforts.
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http://dx.doi.org/10.1016/j.drugpo.2019.07.002DOI Listing
October 2019

Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study.

Clin Infect Dis 2020 05;70(11):2369-2376

Kirby Institute, University of New South Wales, Australia.

Background: In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment.

Methods: SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016-2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations.

Results: At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test-Consumption; range, 1-12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.99) and sharing (OR, 0.87; 95% CI, 0.80-0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94-1.02) or alcohol use (OR, 0.99; 95% CI, 0.95-1.04).

Conclusions: Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use.

Clinical Trials Registration: SIMPLIFY, NCT02336139; D3FEAT, NCT02498015.
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http://dx.doi.org/10.1093/cid/ciz633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245153PMC
May 2020

Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia.

J Hepatol 2019 08 10;71(2):281-288. Epub 2019 May 10.

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

Background & Aims: Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales, Australia.

Methods: HCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively.

Results: Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04-1.05], 1.08 [95% CI 1.07-1.08], 1.07 [95% CI 1.06-1.07], and 1.05 [95% CI 1.04-1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95-0.99] and 0.96 [95% CI 0.94-0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97-1.03] and 1.01 [95% CI 1.00-1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14-3.58).

Conclusions: In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities.

Lay Summary: Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.
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http://dx.doi.org/10.1016/j.jhep.2019.04.014DOI Listing
August 2019

Hepatitis C virus testing, liver disease assessment and direct-acting antiviral treatment uptake and outcomes in a service for people who are homeless in Sydney, Australia: The LiveRLife homelessness study.

J Viral Hepat 2019 08 2;26(8):969-979. Epub 2019 May 2.

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

People who are homeless have increased hepatitis C virus (HCV) infection risk, and are less likely to access primary healthcare. We aimed to evaluate HCV RNA prevalence, liver disease burden, linkage to care and treatment uptake and outcomes among people attending a homelessness service in Sydney. Participants were enrolled in an observational cohort study with recruitment at a homelessness service over eight liver health campaign days. Finger-stick whole-blood samples for Xpert® HCV Viral Load and venepuncture blood samples were collected. Participants completed a self-administered survey and received transient elastography and clinical assessment by a general practitioner or nurse. Clinical follow-up was recommended 2-12 weeks after enrolment. For participants initiating direct-acting antiviral (DAA) therapy, medical records were audited retrospectively and treatment outcome data were collected. Among 202 participants (mean age, 48 years), 82% were male (n = 165), 39% (n = 78) reported ever injecting drugs, of whom 63% (n = 49) injected in the previous month. Overall, 23% (n = 47) had detectable HCV RNA and 6% (n=12) had cirrhosis. HCV RNA prevalence among participants with either injecting or incarceration history was 35% (37/105), compared to 4% (3/73) among participants without these risk factors. Among those with detectable HCV RNA, 23 (49%) commenced therapy, of whom 65% (n = 15) achieved sustained virological response, while the remainder had no available treatment outcome. No participant had documented virological failure. HCV DAA treatment uptake among people attending a homelessness service was encouraging, but innovative models of HCV care are required to improve linkage to care and treatment uptake among this highly marginalized population.
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http://dx.doi.org/10.1111/jvh.13112DOI Listing
August 2019

Acceptability and preferences of point-of-care finger-stick whole-blood and venepuncture hepatitis C virus testing among people who inject drugs in Australia.

Int J Drug Policy 2018 11 25;61:23-30. Epub 2018 Oct 25.

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

Background: Uptake of hepatitis C virus (HCV) testing remains inadequate globally. Simplified point-of-care tests should enhance HCV diagnosis and elimination. We aimed to assess the acceptability of finger-stick and venepuncture HCV RNA testing among people who inject drugs (PWID).

Methods: Participants were enrolled in an observational cohort study with recruitment at 13 sites between June 2016 and February 2018. Capillary whole-blood collected by finger-stick and plasma collected by venepuncture were performed for Xpert HCV viral load testing. Participants completed a questionnaire on acceptability of, and preferences for, blood collection methods.

Results: Among 565 participants (mean age, 44 years; 69% male), 64% reported injecting drugs in the last month, and 63% were receiving opioid substitution treatment. Eighty three percent reported that finger-stick testing was very acceptable. Overall, 65% of participants preferred finger-stick over venepuncture testing, with 61% of these preferring to receive results in 60 min. The most common reason for preferring finger-stick over venepuncture testing was it was quick (62%) followed by venous access difficulties (21%). The main reasons for preferring venepuncture over finger-stick testing were that it was quick (61%) and accurate (29%). Females were more likely to prefer finger-stick testing than males (adjusted OR 1.96; 95% CI 1.30, 2.99; p = 0.002). Among people with recent (previous month) injecting drug use, Aboriginal and/or Torres Strait Islander people were less likely than non-Aboriginal people to prefer finger-stick testing (adjusted OR 0.57; 95% CI 0.34, 0.9; p = 0.033).

Conclusions: Finger-stick whole-blood collection is acceptable to people who inject drugs, with males and Aboriginal and/or Torres Strait Islander people with recent injecting drug use less likely to prefer finger-stick testing. Further research is needed to evaluate interventions integrating simplified point-of-care HCV testing to engage people in care in a single-visit, thereby facilitating HCV treatment scale-up.
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http://dx.doi.org/10.1016/j.drugpo.2018.08.011DOI Listing
November 2018

Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy.

Int J Drug Policy 2018 12 29;62:94-103. Epub 2018 Oct 29.

The Kirby Institute, UNSW Sydney, Wallace Wurth Building, UNSW NSW 2052, Australia.

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST.

Methods: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12).

Results: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed.

Conclusion: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.
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http://dx.doi.org/10.1016/j.drugpo.2018.10.004DOI Listing
December 2018

Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: The SIMPLIFY study.

Int J Drug Policy 2018 12 22;62:14-23. Epub 2018 Oct 22.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background: This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection.

Methods: SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics.

Results: Among 103 participants, 97% (n = 100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n = 33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥240 min) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P = 0.944).

Conclusion: This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use.
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http://dx.doi.org/10.1016/j.drugpo.2018.08.013DOI Listing
December 2018

Australia on track to achieve WHO HCV elimination targets following rapid initial DAA treatment uptake: A modelling study.

J Viral Hepat 2019 01 14;26(1):83-92. Epub 2018 Nov 14.

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

Subsidized direct-acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32 600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016-2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub-populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN-based) scenario. During 2016-2030, we estimated an intermediate DAA treatment scenario (2016, 32 600 treated; 2017, 21 370 treated; 2018 17 100 treated; 2019 and beyond, 13 680 treated each year) would avert 40 420 new HCV infections, 13 260 liver-related deaths (15 320 in viraemic; -2060 in cured) and 10 730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN-based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver-related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15 years. The pre-DAA escalation in those with advanced liver disease makes the achievement of the liver-related mortality target difficult.
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http://dx.doi.org/10.1111/jvh.13013DOI Listing
January 2019

Direct-acting antiviral treatment for hepatitis C among people who use or inject drugs: a systematic review and meta-analysis.

Lancet Gastroenterol Hepatol 2018 11 21;3(11):754-767. Epub 2018 Sep 21.

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

Background: There are concerns around poorer response to direct-acting antiviral (DAA) therapy for hepatitis C virus infection among people who use drugs. This systematic review assessed DAA treatment outcomes among people with recent drug use and those receiving opioid substitution therapy.

Methods: Bibliographic databases and conference presentations were searched for observational studies and clinical trials assessing DAA treatment completion, sustained virological response (SVR), and loss to follow-up among people with recent drug use (injecting or non-injecting) and those receiving opioid substitution therapy. Meta-analysis was used to pool estimates and meta-regression to explore heterogeneity.

Findings: 38 eligible studies, with 3634 participants, were included. The definition of recent drug use varied across studies, with drug use in the past 6 months and at the initiation of or during DAA therapy most commonly used. Among individuals with recent injecting or non-injecting drug use (21 studies; 1408 participants), treatment completion was 97·5% (95% CI 96·6-98·3) and SVR was 87·7% (95% CI 84·2-91·3). Among individuals receiving opioid substitution therapy (36 studies; 2987 participants), treatment completion was 97·4% (95% CI 96·5-98·3) and SVR was 90·7% (95% CI 88·5-93·0). Among individuals with recent injecting drug use (eight studies; 670 participants), treatment completion was 96·9% (95% CI 95·6-98·2) and SVR was 87·4% (95% CI 82·0-92·8). In meta-regression analysis, clinical trials (vs observational studies; adjusted odd ratio 2·18, 95% CI 1·27-3·75; p=0·006) and higher mean or median age (1·07, 1·02-1·12; p=0·008) were significantly associated with higher SVR. Clinical trials (0·45, 0·22-0·94; p=0·033) and older age (0·94, 0·88-0·99; p=0·034) were also significantly associated with a lower proportion of participants lost to follow-up.

Interpretation: Response to DAA therapy was favourable among people with recent drug use (including those who inject) and those receiving opioid substitution therapy, supporting broadening access in these populations.

Funding: The Kirby Institute, UNSW Sydney, and National Health and Medical Research Council of Australia.
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http://dx.doi.org/10.1016/S2468-1253(18)30304-2DOI Listing
November 2018

Modeling of patient virus titers suggests that availability of a vaccine could reduce hepatitis C virus transmission among injecting drug users.

Sci Transl Med 2018 07;10(449)

Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.

The major route of hepatitis C virus (HCV) transmission in the United States is injection drug use. We hypothesized that if an HCV vaccine were available, vaccination could affect HCV transmission among people who inject drugs by reducing HCV titers after viral exposure without necessarily achieving sterilizing immunity. To investigate this possibility, we developed a mathematical model to determine transmission probabilities relative to the HCV RNA titers of needle/syringe-sharing donors. We simulated sharing of two types of syringes fitted with needles that retain either large or small amounts of fluid after expulsion. Using previously published viral kinetics data from both naïve subjects infected with HCV and reinfected individuals who had previously cleared an HCV infection, we estimated transmission risk between pairs of serodiscordant injecting drug users, accounting for syringe type, rinsing, and sharing frequency. We calculated that the risk of HCV transmission through syringe sharing increased ~10-fold as viral titers (log IU/ml) increased ~25-fold. Cumulative analyses showed that, assuming sharing episodes every 7 days, the mean transmission risk over the first 6 months was >90% between two people sharing syringes when one had an HCV RNA titer >5 log IU/ml. For those with preexisting immunity that rapidly controlled HCV, the cumulative risk decreased to 1 to 25% depending on HCV titer and syringe type. Our modeling approach demonstrates that, even with transient viral replication after exposure during injection drug use, HCV transmission among people sharing syringes could be reduced through vaccination if an HCV vaccine were available.
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http://dx.doi.org/10.1126/scitranslmed.aao4496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552668PMC
July 2018

Evaluation of a Hepatitis C Virus Core Antigen Assay in Plasma and Dried Blood Spot Samples.

J Mol Diagn 2018 09 26;20(5):621-627. Epub 2018 Jun 26.

Kirby Institute, University of New South Wales, Sydney, Australia. Electronic address:

Simplified, affordable tools to diagnose active hepatitis C virus (HCV) infection are needed to scale up treatment. This study evaluated the analytical performance of HCV core antigen (HCVcAg) detection in samples of plasma and dried venous blood spots (DBSs). Paired plasma and DBS samples were prepared from remnant diagnostic samples, and plasma HCV RNA and HCVcAg were quantified. Sensitivity and specificity for HCVcAg (>3 fmol/L) at two HCV RNA thresholds (≥15 and ≥3000 IU/mL) were calculated. Of 120 paired samples tested, 25 had nonquantifiable HCV RNA and 95 had quantifiable HCV RNA. The median HCV RNA level in plasma was 5.6 log IU/mL (interquartile range: 5.2 to 6.2). The median HCVcAg levels in plasma and DBS samples were 2.3 log fmol/L (interquartile range: 0.1 to 3.1) and 1.1 log fmol/L (interquartile range: 0.0 to 1.9), respectively. For diagnosing HCV RNA ≥3000 IU/mL, the sensitivity and specificity of HCVcAg in plasma were 97.7% (95% CI, 91%-100%) and 100% (95% CI, 87%-100%), respectively. The sensitivity and specificity of HCVcAg in DBS were 88.6% (95% CI, 80%-94%) and 97% (95% CI, 82%-100%), respectively. The data from this study demonstrate good sensitivity and specificity of HCVcAg in plasma at an HCV RNA threshold of ≥3000 IU/mL. The level of HCVcAg quantified in plasma was higher than that in DBS.
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http://dx.doi.org/10.1016/j.jmoldx.2018.05.010DOI Listing
September 2018