Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

BACKGROUND AND AIMS: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. APPROACH AND RESULTS: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. CONCLUSIONS: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

Annual hepatitis C testing and positive tests among gay and bisexual men in Australia from 2016 to 2022: a serial cross-sectional analysis of sentinel surveillance data.

OBJECTIVE: Guidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of HCV testing among GBM. We aimed to examine trends in HCV testing and positivity from 2016 to 2022. METHODS: Using sentinel surveillance data, we examined the proportion of GBM with at least one test and the proportion with a positive test in each year for HCV antibody testing among GBM with no previous HCV positive test, HCV RNA testing among GBM with a positive antibody test but no previous positive RNA test (naïve RNA testing), and HCV RNA testing among people who had a previous RNA positive test and a subsequent negative test (RNA follow-up testing). Trends were examined using logistic regression from 2016 to 2019 and 2020 to 2022. RESULTS: Among GBM with HIV, from 2016 to 2019 antibody testing was stable averaging 55% tested annually. Declines were observed for both naïve HCV RNA testing (75.4%-41.4%: p<0.001) and follow-up HCV RNA testing (70.1%-44.5%: p<0.001). Test positivity declined for HCV antibody tests (2.0%-1.3%: p=0.001), HCV RNA naïve tests (75.4%-41.4%: p<0.001) and HCV RNA follow-up tests (11.3%-3.3%: p=0.001). There were minimal or no significant trends from 2020 to 2022.Among GBM prescribed PrEP, antibody testing declined from 2016 to 2019 (79.4%-69.4%: p<0.001) and was stable from 2020 to 2022. Naïve and follow-up HCV RNA testing was stable with an average of 55% and 60% tested each year, respectively. From 2016-2019, the proportion positive from HCV RNA naïve tests declined (44.1%-27.5%: p<0.046) with no significant change thereafter. Positive follow-up HCV RNA tests fluctuated with no or one new positive test among this group in most years. CONCLUSION: The proportion of GBM with positive HCV tests has declined, however a substantial proportion are not tested annually. A renewed focus on HCV testing, and treatment where required, is warranted to achieve HCV elimination among GBM in Australia.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

BACKGROUND: There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. METHODS: Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. RESULTS: Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). CONCLUSION: HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

Validation of a novel point-of-care test for alanine aminotransferase measurement: A pilot cohort study.

BACKGROUND: Alanine aminotransferase (ALT) measurement is essential for evaluation of liver disease. We validated a novel rapid point-of-care (POC) test for ALT1 against laboratory ALT. METHODS: Stored plasma samples from adults with chronic liver disease (Test cohort n = 240; Validation cohort n = 491) were analysed using the BioPoint® antigen immunoassay POC ALT1 lateral flow test, which provides quantitative ALT results (Axxin handheld reader) or semi-quantitative results (visual read, cut off 40 IU/ml). The accuracy of POC ALT1 to detect ALT > 40 IU/L was determined by ROC analysis. In patients with chronic hepatitis B, treatment eligibility (EASL criteria) was determined using POC ALT1 and compared to laboratory ALT. RESULTS: POC ALT1 test had good accuracy for laboratory ALT > 40 IU/L: AUROC 0.93 (95% CI: 0.89-0.96) in the Test cohort and AUROC 0.92 (95% CI: 0.88-0.95) in the Validation cohort. POC ALT1 cut off of 0.8 for ALT > 40 IU/L maximised sensitivity (97%) and specificity (71%) in the Test cohort (42% laboratory ALT > 40 IU/L) and yielded PPV 84% and NPV 91% in the Validation cohort (19% laboratory ALT > 40 IU/L). Semi-quantitative POC ALT1 had good accuracy for laboratory ALT in the Validation cohort (AUROC 0.85, 95% CI: 0.81-0.99; sensitivity 77% and specificity 93%). Combined with HBV DNA and transient elastography, both quantitative and semi-quantitative POC ALT1 tests had good accuracy for excluding hepatitis B treatment needs (sensitivity 96%, specificity 78% and NPV 99%). CONCLUSION: The POC ALT1 test had good accuracy for elevated ALT levels and for determining treatment eligibility among people with chronic hepatitis B.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs.

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31-36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25-30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

Evaluation of a person-centred, nurse-led model of care delivering hepatitis C testing and treatment in priority settings: a mixed-methods evaluation of the Tasmanian Eliminate Hepatitis C Australia Outreach Project, 2020-2022.

INTRODUCTION: Australia has experienced sustained reductions in hepatitis C testing and treatment and may miss its 2030 elimination targets. Addressing gaps in community-based hepatitis C prescribing in priority settings that did not have, or did not prioritise, hepatitis C testing and treatment care pathways is critical. METHODS: The Tasmanian Eliminate Hepatitis C Australia Outreach Project delivered a nurse-led outreach model of care servicing hepatitis C priority populations in the community through the Tasmanian Statewide Sexual Health Service, supported by the Eliminating Hepatitis C Australia partnership. Settings included alcohol and other drug services, needle and syringe programs and mental health services. The project provided clients with clinical care across the hepatitis C cascade of care, including testing, treatment, and post-treatment support and hepatitis C education for staff. RESULTS: Between July 2020 and July 2022, a total of 43 sites were visited by one Clinical Nurse Consultant. There was a total of 695 interactions with clients across 219 days of service delivery by the Clinical Nurse Consultant. A total of 383 clients were tested for hepatitis C (antibody, RNA, or both). A total of 75 clients were diagnosed with hepatitis C RNA, of which 95% (71/75) commenced treatment, 83% (62/75) completed treatment and 52% (39/75) received a negative hepatitis C RNA test at least 12 weeks after treatment completion. CONCLUSIONS: Providing outreach hepatitis C services in community-based services was effective in engaging people living with and at-risk of hepatitis C, in education, testing, and care. Nurse-led, person-centred care was critical to the success of the project. Our evaluation underscores the importance of employing a partnership approach when delivering hepatitis C models of care in community settings, and incorporating workforce education and capacity-building activities when working with non-specialist healthcare professionals.

The Incidence of Hepatitis C Among Gay, Bisexual, and Other Men Who Have Sex With Men in Australia, 2009-2019.

BACKGROUND: Hepatitis C virus (HCV) infection has been reported among gay, bisexual, and other men who have sex with men (GBM) globally including GBM with human immunodeficiency virus (HIV) and HIV-negative GBM, particularly those using HIV preexposure prophylaxis (PrEP). In Australia, HCV direct-acting antiviral treatment (DAA) was government-funded from 2016. Large implementation studies of PrEP also began in 2016. We examined HCV incidence among GBM to assess whether HCV incidence has changed since 2015. METHODS: Data were drawn from the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. We included GBM who tested HCV antibody negative at their first test and had ≥1 subsequent test. Generalized linear modeling (Poisson distribution) was used to examine HCV incidence from 2009 to 2019 stratified by HIV status, and among HIV-negative GBM prescribed PrEP from 2016 to 2019. RESULTS: Among 6744 GBM with HIV, HCV incidence was 1.03 per 100 person-years (PY). Incidence declined by 78% in 2019 compared to 2015 (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}: .09-.55]). Among 20 590 HIV-negative GBM, HCV incidence was 0.20/100 PY, with no significant change over time. Among 11 661 HIV-negative GBM prescribed PrEP, HCV incidence was 0.29/100 PY. Compared to 2016, incidence among GBM prescribed PrEP declined by 80% in 2019 (IRR, 0.20 [95% CI: .06-.64]). CONCLUSIONS: HCV incidence among GBM living with HIV declined following DAA availability. There was no observed change in HCV incidence among HIV-negative GBM overall. Among GBM prescribed PrEP, incidence declined since the early years of PrEP implementation in Australia. Australia is on track to eliminate HCV among GBM before global 2030 targets.

Retreatment for hepatitis C virus direct acting antiviral therapy virological failure in primary and tertiary settings: the REACH-C cohort.

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n=10843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n=56) and tertiary (n=157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per-protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p=1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11-0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64-11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15-0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralised models may increase retreatment uptake and reduce HCV-related mortality.

The impact of point-of-care hepatitis C testing in needle and syringe exchange programs on linkage to care and treatment uptake among people who inject drugs: An Australian pilot study.

Point-of-care (POC) diagnostics overcome barriers to conventional hepatitis C (HCV) testing in people who inject drugs. This study assessed impact on hepatitis C treatment uptake of POC HCV testing in needle and syringe exchange programs (NSPs). Rapid EC was a single-arm interventional pilot study of HCV POC testing conducted in three inner-city community clinics with NSPs. Twelve months after the POC testing, a retrospective medical record and Pharmaceutical Benefits Scheme audit was performed to determine the number of HCV RNA-positive participants who were prescribed HCV treatment. 70 HCV RNA-positive Rapid EC study participants were included. 44 (63%) were prescribed DAAs; 26 (59%) completed treatment and 15 (34%) had SVR testing, all of whom were cured. Age ≥ 40 years (aOR 3.45, 95% CI 1.10-11.05, p = .03) and secondary school education (aOR 5.8, 95% CI 1.54-21.80, p = .009) had higher likelihood of being prescribed DAAs, whereas homelessness was inversely associated with prescription of DAAs (aOR 0.30, 95% CI 0.09-1.04, p = .057). Median time to receive a DAA script from date of diagnosis was seven days (IQR 0 to 14 days), and time to filling the DAA prescription was 2 days (IQR 0-12 days). In conclusion, provision of POC testing through NSPs was effective for linking new clients to HCV treatment and reduced the time to treatment. Further studies are needed to define the most cost-effective use of POC testing in models of care for people who inject drugs to increase HCV treatment uptake.

Impact of COVID-19 lockdown restrictions on hepatitis C testing in Australian primary care services providing care for people who inject drugs.

In 2020, the Australian state of Victoria experienced the longest COVID-19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de-identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time-series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C.

A multi-site, nurse-coordinated hepatitis C model of care in primary care and community services in Melbourne, Australia.

BACKGROUND: Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS: People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS: Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION: A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

Review of management priorities for invasive infections in people who inject drugs: highlighting the need for patient-centred multidisciplinary care.

There has been a global increase in the burden of invasive infections in people who inject drugs (PWID). It is essential that patient-centred multidisciplinary care is provided in the management of these infections to engage PWID in care and deliver evidence-based management and preventive strategies. The multidisciplinary team should include infectious diseases, addictions medicine (inclusive of alcohol and other drug services), surgery, psychiatry, pain specialists, pharmacy, nursing staff, social work and peer support workers (where available) to help address the comorbid conditions that may have contributed to the patient's presentation. PWID have a range of antimicrobial delivery options that can be tailored in a patient-centred manner and thus are not limited to prolonged hospital admissions to receive intravenous antimicrobials for invasive infections. These options include discharge with outpatient parenteral antimicrobial therapy, long-acting lipoglycopeptides (dalbavancin and oritavancin) and early oral antimicrobials. Open and respectful discussion with PWID including around harm reduction strategies may decrease the risk of repeat presentations with injecting-related harms.

Microelimination of Hepatitis C Among People With Human Immunodeficiency Virus Coinfection: Declining Incidence and Prevalence Accompanying a Multicenter Treatment Scale-up Trial.

BACKGROUND: Gay and bisexual men (GBM) are a key population affected by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We aimed to measure HCV treatment effectiveness and to determine the population impact of treatment scale-up on HCV prevalence and incidence longitudinally among GBM. METHODS: The co-EC Study (Enhancing Care and Treatment Among HCV/HIV Coinfected Individuals to Eliminate Hepatitis C Transmission) was an implementation trial providing HCV direct-acting antiviral treatment in Melbourne, Australia, during 2016-2018. Individuals with HCV/HIV coinfection were prospectively enrolled from primary and tertiary care services. HCV viremic prevalence and HCV antibody/viremic incidence were measured using a statewide, linked, surveillance system. RESULTS: Among 200 participants recruited, 186 initiated treatment during the study period. Sustained virological response in primary care (98% [95% confidence interval {CI}, 93%-100%]) was not different to tertiary care (98% [95% CI, 86%-100%]). From 2012 to 2019, between 2434 and 3476 GBM with HIV infection attended our primary care sites annually, providing 13 801 person-years of follow-up; 50%-60% received an HCV test annually, and 10%-14% were anti-HCV positive. Among those anti-HCV positive, viremic prevalence declined 83% during the study (54% in 2016 to 9% in 2019). HCV incidence decreased 25% annually from 1.7/100 person-years in 2012 to 0.5/100 person-years in 2019 (incidence rate ratio, 0.75 [95% CI, .68-.83]; P < .001). CONCLUSIONS: High treatment effectiveness by nonspecialists demonstrates the feasibility of treatment scale-up in this population. Substantial declines in HCV incidence and prevalence among GBM provides proof-of-concept for HCV microelimination. CLINICAL TRIALS REGISTRATION: NCT02786758.

A modelling analysis of financial incentives for hepatitis C testing and treatment uptake delivered through a community-based testing campaign.

Financial incentives may reduce opportunity costs associated with people who become lost to follow-up in hepatitis C treatment programs. We estimated the impact that different financial incentive amounts would need to have on retention in care to maintain the same unit cost per (1) RNA-positive person completing testing (defined as awareness of RNA status) and (2) RNA diagnosed person initiating treatment. Costing data were obtained from a 2019 community-based testing campaign focused on engaging people who inject drugs. For different financial incentive amounts, we modelled the corresponding improvements in retention in care that would be needed to maintain the same overall (1) unit cost per testing completion and (2) unit cost per treatment initiation. In the testing campaign, the unit cost per RNA-positive person completing testing was A$3215 and the unit cost per RNA diagnosed person initiating treatment was A$1055. Modelling found that an incentive of A$500 per RNA-positive person completing testing would result in more people completing testing for the same unit cost if the percentage of attendees receiving their test results increased from 63% to 74%. An incentive of A$200 per RNA diagnosed person initiating treatment would result in more people initiating treatment for the same unit cost if the percentage initiating treatment increased from 67% to 83%. Monetary incentives for completing testing and initiating treatment may be an effective way to increase retention in care without increasing the overall unit cost of completing testing/initiating treatment.

Patient-reported outcomes of the Treatment and Prevention Study: A real-world community-based trial of direct-acting antivirals for hepatitis C among people who inject drugs.

The impact of hepatitis C cure with direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) in community settings remains unclear. We aimed to assess changes in PROs over time and whether treatment was associated with sustained improved PROs in a cohort of people who inject drugs. This study is a sub-analysis of the Treatment and Prevention Study, a nurse-led trial where people who inject drugs and their injecting partners were recruited in a community setting, in Melbourne, Australia. Three participant groups were characterized: treatment, untreated and non-viremic (hepatitis C RNA negative at screening). PROs included assessment of health-related quality of life using the Short Form-8 (SF-8) Survey and life satisfaction using Personal Wellbeing Index (PWI). PROs were measured at baseline and every 12 weeks until week 84. Generalized estimating equations were used to measure whether treatment was associated with longitudinal PRO change. A total of 215 participants were included in this analysis. PWI scores were significantly higher at week 12 for both treatment group (p = 0.0309) and non-viremic group (p = 0.0437) compared to baseline. However, treatment was not associated with longitudinal change in PRO scores. In conclusion, we found DAA treatment did not significantly improve PRO scores compared to those not receiving treatment and without hepatitis C. The measures used in this study may not be sensitive enough to capture the hepatitis C specific improvements in quality of life that treatment affords or factors other than treatment may be influencing quality of life scores in this cohort.

Hepatitis C treatment in a co-located mental health and alcohol and drug service using a nurse-led model of care.

Hepatitis C virus (HCV) is more prevalent among people with experience of severe mental illness compared to the general population, due in part to higher levels of injecting drug use. Delivering HCV care through mental health services may reduce barriers to care and improve outcomes. A nurse-led HCV program was established in a co-located mental health and addiction service in Melbourne, Australia. People with a history of injecting drug use, including current use, were referred for HCV testing by nurses, with support provided on-site from a general practitioner and remotely from infectious disease and hepatology specialists. A nurse practitioner, general practitioner or specialists were able to prescribe HCV treatment. One-hundred and thirty people were referred to the nurse-led service, among whom 112 (86%) were engaged in care. Of those 112, 84 (75%) were found to have detectable HCV RNA, 70 (83%) commenced treatment; 28 (40%) prescriptions were nurse initiated, 19 (27%) were general practitioner initiated and 20 (29%) were prescribed from hospital clinics or elsewhere. All people with an SVR result (48/70) achieved HCV cure (intention to treat SVR 69%, per-protocol SVR 100%). Treatment commencement was highest among people prescribed opioid agonist therapy (28/29, 96%) compared to those who were not (18/26, 69%). In conclusion, a nurse-led, HCV service for people with severe mental illness including pathways to specialist support when needed can achieve high treatment uptake and cure. Further implementation work is required to improve treatment uptake, particularly among people not prescribed opioid agonist therapy, and to improve follow-up for SVR testing.

Real-world monitoring progress towards the elimination of hepatitis C virus in Australia using sentinel surveillance of primary care clinics; an ecological study of hepatitis C virus antibody tests from 2009 to 2019.

To achieve the elimination of the hepatitis C virus (HCV), sustained and sufficient levels of HCV testing is critical. The purpose of this study was to assess trends in testing and evaluate the effectiveness of strategies to diagnose people living with HCV. Data were from 12 primary care clinics in Victoria, Australia, that provide targeted services to people who inject drugs (PWID), alongside general health care. This ecological study spanned 2009-2019 and included analyses of trends in annual numbers of HCV antibody tests among individuals with no previous positive HCV antibody test recorded and annual test yield (positive HCV antibody tests/all HCV antibody tests). Generalised linear models estimated the association between count outcomes (HCV antibody tests and positive HCV antibody tests) and time, and χ2 test assessed the trend in test yield. A total of 44 889 HCV antibody tests were conducted 2009-2019; test numbers increased 6% annually on average [95% confidence interval (CI) 4-9]. Test yield declined from 2009 (21%) to 2019 (9%) (χ2P = <0.01). In more recent years (2013-2019) annual test yield remained relatively stable. Modest increases in HCV antibody testing and stable but high test yield within clinics delivering services to PWID highlights testing strategies are resulting in people are being diagnosed however further increases in the testing of people at risk of HCV or living with HCV may be needed to reach Australia's HCV elimination goals.

Perceived physical health outcomes of direct-acting antiviral treatment for hepatitis C: a qualitative study.

BACKGROUND: Novel health promotion and treatment uptake initiatives will be necessary to ensure Australia meets 2030 hepatitis C elimination targets. Increasing treatment uptake will be assisted by a better understanding of the treatment experience and patient-perceived benefits. This study describes the perceived physical health benefits from direct-acting antiviral (DAA) hepatitis C treatment among people who inject drugs in Melbourne, Australia. METHODS: Twenty participants were recruited from a community treatment trial and community health clinics. Semi-structured interviews were performed with each participant before, during and following treatment. Interviews focused on treatment experiences, attitudes and motivations. Interviews were recorded, transcribed and thematically analysed. RESULTS: Two themes relating to the physical experience of treatment developed; intersection between physical and mental health and "maybe it's working". Participants reported various physical benefits, most prominently, reduced fatigue. Reductions in fatigue resulted in instant and meaningful changes in everyday life. Some participants did experience side effects, which they described as mild. Experiencing noticeable physical benefits during treatment was perceived as validation that treatment was working. CONCLUSION: Physical health benefits of DAA treatment may have carry-on effects on cognitive, emotional or social wellbeing and should be incorporated into how treatment is promoted to those who require it.

Outcomes of Treatment for Hepatitis C in Primary Care, Compared to Hospital-based Care: A Randomized, Controlled Trial in People Who Inject Drugs.

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to direct-acting antivirals (DAAs), especially among people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care, compared with hospital-based specialist care. METHODS: We randomized PWID with HCV attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care [SOC]). The primary outcome was to determine whether people treated in primary care had a noninferior rate of sustained virologic response at Week 12 (SVR12), compared to historical controls (consistent with DAA trials at the time of the study design); secondary outcomes included comparisons of treatment initiation, SVR12 rates, and the care cascade by study arm. RESULTS: We recruited 140 participants and randomized 136: 70 to the primary care arm and 66 to the SOC arm. The SVR12 rate (100%, 95% confidence interval [CI] 87.7-100) of people treated in primary care was noninferior when compared to historical controls (85% assumed). An intention-to-treat analysis revealed that the proportion of participants commencing treatment in the primary care arm (75%, 43/57) was significantly higher than in the SOC arm (34%, 18/53; P < .001; relative risk [RR] 2.48, 95% CI 1.54-3.95), and the proportion of participants with SVR12 was significantly higher in the primary care arm, compared to in the SOC arm (49% [28/57] and 30% [16/53], respectively; P = .043; RR 1.63, 95% CI 1.0-2.65). CONCLUSIONS: Providing HCV treatment in primary care increases treatment uptake and cure rates. Approaches that increase treatment uptake among PWID will accelerate elimination strategies. CLINICAL TRIALS REGISTRATION: NCT02555475.