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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.

Australia was one of the first countries with unrestricted access to government subsidized direct-acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real-world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow-up. Real-world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH-C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention-to-treat (ITT) and per-protocol (PP) analyses. Within REACH-C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43-0.72), cirrhosis (aOR 0.52, 95% CI 0.41-0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46-0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28-0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow-up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44-2.11; IDU + OAT: aOR 1.39, 95% CI 1.11-1.74; OAT only, aOR 1.36; 95% CI 1.13-1.68) and age (aOR 0.97, 95% CI 0.97-0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow-up presents a real-world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow-up.

Naloxone is a life-saving medication that reverses opioid overdose; naloxone can be provided on a 'take-home' basis so naloxone can be administered outside of the health-care setting. The Overdose Response and Take Home Naloxone (ORTHN) project established a model of care for take-home naloxone (THN) interventions across alcohol and other drug and harm reduction services in NSW, Australia. This paper evaluates the staff training and credentialing program, and examines staff attitudes and perspectives regarding the provision of THN interventions in these settings.Staff across seven services were trained through a 'train-the-trainer' credentialing model to deliver ORTHN, including naloxone supply. Staff were surveyed regarding their experience, attitudes and knowledge on THN prior to and after training, and after 6 months. At the 6 months follow up, staff were asked about the interventions they provided, barriers and enablers to uptake, and opinions regarding future rollout.A total of 204 staff were trained and credentialed to provide the ORTHN intervention. Most (60%) were nurses, followed by needle syringe program workers and allied health/counsellors (32%). Linear and logistic regression analyses indicated that the training program was associated with significant improvements in staff knowledge and attitudes towards overdose and THN; however, only attitudinal improvements were maintained over time. There were high rates of staff satisfaction with the ORTHN intervention and training.The ORTHN program is 'fit for purpose' for broad implementation in these settings. A number of potential barriers (e.g. time, medication and staffing costs) and enablers (e.g. peer engagement, regulatory framework for naloxone supply) in implementing THN interventions were identified.

Objective(s) To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia. Design Prospective observational cohort study (2014-2018). Methods Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018. Results Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44-2.53). Conclusion No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.

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.

Background The use of preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has raised concerns of increased sexual risk behaviors. These behaviors may be associated with increased incidence of sexually acquired hepatitis C virus (HCV) among gay and bisexual men. Methods The Expanded PrEP Implementation in Communities–New South Wales (EPIC-NSW) study was a cohort study of daily coformulated tenofovir disoproxil fumarate and emtricitabine for HIV prevention. We recruited 9596 people at high risk of HIV acquisition from 31 clinics across New South Wales and the Australia Capital Territory in Australia. We report prior exposure to HCV and incidence in this cohort between 2016 and 2019. Results At least 1 HCV test result was available for 8658 (90.2%) participants. These individuals had a median age of 34 years (interquartile range, 28–43), most of whom were male (8530, 98.5%), identified as gay (7944, 91.8%), and were born in Australia (51.8%). Prior exposure to HCV was detected among 81 participants at baseline (0.9%; 95% confidence interval [CI]: .71.2). Twenty of 8577 participants were diagnosed with incident infection (rate 0.2/100 person-years [95% CI: .1–.3/100 person-years]). They were significantly older (median age 41 years vs 34 years, P = .044), and more likely to report methamphetamine use at baseline (incidence rate ratio, 2.7 [95% CI: 1.00–7.2]) than those without incident infection. Conclusions In this population of PrEP users, HCV prior exposure and incidence were low. With high levels of HCV and HIV testing and treatment, the dual goals of HIV and HCV elimination could be achieved in this population. Clinical Trials Registration: number NCT02870790.

Background & Aims Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. Methods REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. Results The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4–89.0) in the short arm and 86/95, 90.5% (95% CI 82.7–95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8–95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0–99.7; difference -8.3%, p = 0.025). Conclusions In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. Lay summary In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. ClinicalTrials.gov Identifier NCT02625909 .

Awareness of hepatitis C virus (HCV) infection status among people who inject drugs (PWID) can empower people with diagnosis, enable treatment uptake, and facilitate elimination. We aimed to evaluate awareness of HCV infection status among a large national cohort of PWID in an era of unrestricted HCV treatment.ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire containing self-reported HCV data (including infection status: never tested, tested/unknown, no current HCV infection [HCV RNA not detectable], current HCV infection [HCV RNA detectable]) and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Awareness was defined as concordant self-reported HCV status and test result. Awareness was assessed among all participants, those with current HCV infection, and participants who reported a lifetime history of HCV treatment. Logistic regression was used to assess factors associated with awareness in these three populations.Among 2,305 PWID, 65% (n=1,506) were aware of their HCV infection status (self-reported HCV status matched HCV point-of-care result). Awareness of infection status was higher among those who were not currently infected (70%, n=1,281/1,818) compared to those with current HCV infection (46%, n=225/487). After adjusting, those with current HCV infection were less likely to be aware of infection status (aOR: 0.40, 95%CI: 0.30, 0.45). Among those who reported a lifetime history of HCV treatment, 71% (n=592/829) were aware of their HCV infection status.Among a large cohort of PWID in Australia, awareness of HCV infection status is sub-optimal, with particularly concerning levels among those with active infection. Increased and simplified testing, post-test counselling, and post-treatment monitoring is warranted.

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 that assessed the association between OAT and HCV testing, treatment, and treatment outcomes (direct-acting antiviral [DAA] therapy only) among PWID (in the past year). Meta-analysis was used to pool estimates. Results Of 9877 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 1 study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing (4 studies; odds ratio (OR), 1.80; 95% confidence interval [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 OAT 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.

Injecting-related skin and soft tissue infections (SSTIs) are a preventable cause of inpatient hospitalisation among people who inject drugs (PWID). This study aimed to determine the prevalence of hospitalisation for SSTIs among PWID, and identify similarities and differences in factors associated with hospitalisation for SSTIs versus non-bacterial harms related to injecting drug use.We performed cross-sectional analyses of baseline data from an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Logistic regression models were used to identify factors associated with self-reported hospitalisation for (1) SSTIs (abscess and/or cellulitis), and (2) non-bacterial harms related to injecting drug use (e.g., non-fatal overdose; hereafter referred to as non-bacterial harms), both together and separately.1851 participants who injected drugs in the previous six months were enrolled (67% male; 85% injected in the past month; 42% receiving opioid agonist treatment [OAT]). In the previous year, 40% (n = 737) had been hospitalised for drug-related causes: 20% (n = 377) and 29% (n = 528) of participants were admitted to hospital for an SSTI and non-bacterial harm, respectively. Participants who were female (adjusted odds ratio [aOR]: 1.53, 95% CI: 1.19-1.97) or homeless (aOR: 1.59, 95% CI: 1.16-2.19) were more likely to be hospitalised for an SSTI, but not a non-bacterial harm. Both types of hospitalisation were more likely among people recently released from prison.Hospitalisation for SSTIs is common among PWID. Community-based interventions to prevent SSTIs and subsequent hospitalisation among PWID will require targeting of at-risk groups, including women, people experiencing homelessness, and incarcerated people upon prison release.

A community-based public health facility in Sydney, Australia, the Kirketon Road Centre (KRC), provides health care to people who inject drugs (PWID), homeless and other marginalized people. Since March 2016, KRC has provided treatment for chronic hepatitis C virus (HCV) with direct-acting antivirals (DAAs). We aimed to evaluate treatment adherence amongst clients taking DAAs in a highly marginalized population. All clients who commenced DAA therapy prior to March 2018 at KRC were included in this observational cohort with a subset of clients attending daily or weekly for enhanced adherence support and dosing. Demographic, behavioural, clinical measures and medication dosing were recorded, and adherence was calculated as the proportion of doses taken during the expected treatment duration. Factors associated with adherence were examined using logistic regression. A total of 242 individuals commenced DAA therapy, of whom 79 (32%) received enhanced adherence support. Enhanced support was associated with homelessness, daily injecting, Aboriginality, mental health co-morbidity and poly-drug use (all P < .001). Overall adherence was 86%, and 92% of patients missed one or more doses (median 10, IQR 4-24). At least 90% adherence during planned duration was seen in 38%, but increased to 66% by continuing therapy beyond planned duration. Intention-to-treat SVR12 was 68% and 66% in the enhanced adherence support sub-population, with 29% lost to follow-up by SVR12 testing. There were only 2 (0.8%) documented virological failures. Per-protocol SVR12 was 99% and 96% in the enhanced adherence support sub-population. In conclusion, adherence support may benefit those with multiple markers of marginalization. Extension of therapy beyond planned duration is a pragmatic strategy to enhance completion. Strategies to improve follow-up, particularly post-treatment are required.

Introduction and aims To maximise the benefits of direct acting antivirals in Australia, innovative options for marginalised populations to receive daily or weekly medication may be beneficial. This study evaluated the feasibility and acceptability of direct acting antivirals provision by leveraging an opioid agonist treatment program to support adherence regardless of opioid agonist treatment enrolment. Design and methods Feasibility was evaluated by monitoring selection of dosing options by clients initiating direct acting antivirals during the first 6 months. Client acceptability was assessed using a cross-sectional survey after 6 months. Pre- and post-implementation surveys of attitudes and concerns regarding the program were compared to evaluate staff acceptability. Results Among 79 clients commencing direct acting antivirals, 30 (38%) chose adherence support. Among these, 12 (40%) were not simultaneously enrolled in opioid agonist treatment. Clients were satisfied with service provision and access despite introducing daily dosing. All highly marginalised clients receiving direct acting antivirals with adherence support found this helpful. Staff concerns identified prior to the program proved unfounded. Discussion and conclusions This study demonstrates providing adherence support for direct acting antivirals regardless of client participation in opioid agonist treatment is both feasible and acceptable with minimal impact on service provision. Availability of direct acting antivirals in opioid agonist treatment or primary health-care settings expands the pool of people who may receive effective treatment for hepatitis C virus and reduces treatment barriers.

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 (

Summary Background HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. Methods The Expanded PrEP Implementation in Communities–New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov , number NCT02870790 . Findings We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30–45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012–0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5–37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI −4·5 to 36·6). Interpretation PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. Funding New South Wales Ministry of Health, Gilead Sciences.

Background Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). Methods ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. Results Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68–9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29–3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. Conclusions Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

OBJECTIVES To evaluate the impact of government HIV strategies that aimed to increase HIV testing uptake and frequency among gay and bisexual men (GBM) in New South Wales (NSW), Australia. DESIGN We analysed HIV testing data from existing passive and sentinel surveillance systems between 2010 and 2018. METHODS Six indicators were measured: (1) state-wide total HIV laboratory tests; (2) number of GBM attending publicly-funded clinics; (3) 12-monthly testing uptake; (4) annual testing frequency; (5) HIV testing with a STI diagnosis; and (6) HIV positivity. Mathematical modelling was used to estimate (7) the proportion of men with undiagnosed HIV. Indicators were stratified by Australian vs. overseas-born. RESULTS Overall, 43,560 GBM attended participating clinics (22,662 Australian-born, 20,834 overseas-born) from 2010-2018. Attendees increased from 5,186 in 2010 to 16,507 in 2018. There were increasing trends (p

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 ( 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 ( 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.

Summary Background Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. Methods Expanded PrEP Implementation in Communities–New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov , NCT02870790 . Findings Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13–2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46–3·44). Interpretation HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk. Funding New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.

Background Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. Methods The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). Results Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00–2.16), incarcerated in the previous year (2.04; 1.38–3.02), and those injecting drugs daily or more (2.26; 1.43–2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48–.95), participants who were homeless (.59; .38–.96), and those injecting daily or more (.51; .31–.89). People aged ≥45 years (1.46; 1.06–2.01) and people receiving OAT (2.62; 1.52–4.51) were more likely to report HCV treatment. Conclusions Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment.

Introduction and AimsTraining of consumers is seen as a necessary component of take home naloxone (THN) interventions, with demonstrated improvements in consumer knowledge, attitudes and self-efficacy. However, we query whether re-training is necessary component for individuals renewing naloxone supplies who have previously completed a THN intervention.Design and MethodsA secondary analysis of the Overdose Response and Take Home Naloxone (ORTHN) project, comparing participant characteristics, and changes in knowledge, attitudes and self-efficacy regarding overdose and response, following a brief THN intervention in participants who had previously undertaken THN interventions, compared to those with no prior THN interventions. Data was analysed for those completing both baseline (pre-ORTHN intervention) and follow up (3-months later).ResultsNinety-four participants completed both research interviews, of whom 29 (31%) had previously completed a THN intervention. There were few differences in baseline demographics or overdose histories between the two groups. Knowledge regarding overdose response and naloxone use indicated high baseline levels in both groups. Those with no prior THN training had lower rates of self-efficacy at baseline, and significantly improved following the ORTHN intervention, whereas those with prior THN training had higher baseline levels of self-efficacy, which was maintained following the intervention.Discussion and ConclusionsIndividuals who have previously undertaken a THN intervention may not require repeat training when renewing naloxone supplies, increasing the efficiency of THN interventions.

Syphilis results from infection with the spirochaete Treponema pallidum subsp. pallidum, for which humans are the only known natural host. In adults it is transmitted primarily by sexual contact. The organism gains entry into the body through small breaks in the skin or the intact mucosal surfaces of the genitals, mouth, or anus, and is able to invade and survive in a wide variety of tissues. Since the availability of penicillin, syphilis has become primarily (>90%) a disease of less affluent countries or of minority subpopulations in more affluent countries with poor access to healthcare. It is also a disease of people with rapid rates of partner change (e.g. men who have sex with men and commercial sex workers).

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.

BACKGROUND Despite revised guidelines that no longer exclude people who inject drugs (PWID) from treatment for hepatitis C virus (HCV) infection, many clinicians are reluctant to treat recent PWID. This study aimed to evaluate the efficacy of sofosbuvir and velpatasvir therapy in people with chronic HCV infection and recent injection drug use. METHODS In this open-label, single-arm phase 4 trial (SIMPLIFY), we recruited participants with recent injection drug use (past 6 months) and chronic HCV genotype 1-6 infection from seven countries (19 sites). Participants received oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. Therapy was given in 1-week electronic blister packs to record the time and date of each dose. The primary endpoint was the proportion of patients with sustained virological response 12 weeks after completion of treatment (SVR12; defined as HCV RNA

Background Understanding factors associated with engagement across the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is critical for developing targeted interventions to enhance engagement and further HCV elimination efforts. We describe the CoC among Australian PWID, and identify factors associated with engagement at each stage. Methods As part of the 2018 and 2019 Illicit Drug Reporting System, Australians who regularly inject drugs reported lifetime HCV antibody and RNA testing, treatment uptake and completion. Multivariable logistic regression identified characteristics associated with outcomes. Results Of 1499 participants, 87% reported antibody testing. Of those, 70% reported RNA testing, of whom 60% reported being RNA positive. Among those, 76% reported initiating treatment, 78% of whom completed. Incarceration history (adjusted odds ratio 1.90; 95% confidence interval 1.28–2.82), current opioid agonist treatment (OAT) (1.99; 1.14–3.47), and recent alcohol and other drug (AOD) counselling (2.22; 1.27–3.88) were associated with antibody testing. Incarceration history (1.42; 1.07–1.87), and current OAT (2.07; 1.51–2.86) were associated with RNA testing. Current OAT (1.92; 1.22–3.03) and recent AOD counselling (1.91; 1.16–3.13) were associated with treatment uptake. Methamphetamine as drug injected most often in the last month was associated with reduced odds of antibody (0.41; 0.25–0.66) and RNA testing (0.54; 0.40–0.74), compared to heroin. Conclusion CoC engagement amongst Australian PWID is encouraging, with AOD service engagement associated with testing and treatment. Further efforts to reach those not service engaged, particularly those not receiving OAT or who predominantly inject methamphetamine, are needed to achieve HCV elimination targets.

Background Direct acting antiviral (DAA) therapy is highly effective for hepatitis C virus (HCV) infection, but reinfection following treatment may compromise benefits of cure. This study assessed the real-world effectiveness of treatment for reinfection. Methods Real-world effectiveness of antiviral therapy in chronic hepatitis C (REACH-C) is an observational study evaluating treatment outcomes following sequential DAA initiations across 33 health services in Australia between March 2016-June 2019. Reinfection was defined by post-treatment genotype switch or HCV viraemia after sustained virologic response (SVR12). Results Of the 10,843 individuals initiating DAA therapy post-treatment viraemia was reported in 526 of whom 99 were reinfections. Treatment for reinfection occurred in 88 individuals. In those with available treatment outcomes, SVR12 was similar to initial treatment in the overall REACH-C cohort (95% vs 95%; p = 0.745) and comparable across primary, tertiary, and prison settings. Classifying unknown treatment outcomes as failures, SVR12 for treatment of reinfection was lower than initial treatment in REACH-C (67% vs 81%; p = 0.002), due to higher lost to follow-up. Conclusions Treatment of reinfection is highly effective and can be delivered in non-specialist settings. Access to treatment for reinfection in high-risk populations is crucial to HCV elimination.

Background The Kirketon Road Centre (KRC) is a community-based public health facility in Sydney, Australia, that provides healthcare to people who inject drugs (PWID), including hepatitis C virus (HCV) treatment. From March 2016, the Australian Government has provided access to direct-acting antivirals (DAA) for adults with chronic HCV, without liver disease stage or drug and alcohol use restrictions. The aim of this study was to report DAA treatment outcomes among highly marginalised PWID treated at KRC. Methods All individuals initiating DAA treatment at KRC and due for sustained virological response (SVR12) testing by end 2016 were included. Demographic, drug use behaviour, clinical parameters, adherence support and HCV treatment outcomes, including SVR12 were recorded. Factors associated with SVR12, loss-to-follow-up (LTFU) and delayed SVR12 testing (>SVR16) were assessed by multivariate analysis. SVR12 was assessed by intention-to-treat (ITT) and modified ITT, the latter excluding individuals with an end-of-treatment response (ETR) but no SVR12 assessment, or who postponed their SVR12 date due to treatment interruption. Results A total of 72 individuals commencing DAAs were included, of whom 67% were male, 30% homeless, and 32% Aboriginal. All had a lifetime history of injecting drug use, with 75% having injected within the last six months, and 44% injecting at least weekly; 25% were also enrolled in opioid substitution therapy. Twenty-five (35%) individuals elected to receive an enhanced adherence-support package. Fifty-nine of 72 (82%) individuals due for SVR12 attended for testing, of whom 59/59 (100%) achieved SVR, providing an ITT SVR of 82%. A further six individuals had undetectable HCV RNA at ETR, but no SVR12 assessment, and one interrupted treatment, providing a mITT SVR of 91%. Homelessness was associated with delayed SVR12 testing (OR 24.9 95%CI 2.9–212.8, p=0.003). There was no association between LTFU and frequency of drug injection, last drug injected, or planned treatment duration. Conclusion This study confirms that PWID can be successfully treated for HCV in a real-world setting using an integrated primary health care model. It also demonstrates feasibility to upscale DAA therapy in high-risk PWID populations, with potential individual and population-level public health benefits. Enhanced efforts are required to optimise post-treatment follow-up.

Background Syphilis rates have increased markedly among men who have sex with men (MSM) internationally. We examined trends in syphilis testing and detection of early syphilis among MSM in Australia. Methods Serial cross-sectional analyses on syphilis testing and diagnoses among MSM attending a national sentinel network of 46 clinics in Australia between 2007 and 2014. Results 359313 clinic visits were included. The proportion of MSM serologically tested for syphilis annually increased in HIV-negative (48% to 91%; Ptrend < .0001) and HIV-positive MSM (42% to 77%; Ptrend < .0001). The mean number of tests per man per year increased from 1.3 to 1.6 in HIV-negative MSM (Ptrend < .0001) and from 1.6 to 2.3 in HIV-positive MSM (Ptrend < .0001). 2799 and 1032 syphilis cases were detected in HIV-negative and HIV-positive MSM, respectively. Among HIV-negative MSM, the proportion of infections that were early latent increased from 27% to 44% (Ptrend < .0001), while the proportion that were secondary decreased from 24% to 19% (Ptrend = .030). Among HIV-positive MSM, early latent infections increased from 23% to 45% (Ptrend < .0001), while secondary infections decreased from 45% to 26% (Ptrend = .0003). Among HIV-positive MSM, decreasing secondary syphilis correlated with increasing testing coverage (r = -0.87; P = .005) or frequency (r = -0.93; P = .001). Conclusions Increases in syphilis screening were associated with increased detection of asymptomatic infectious syphilis and relative falls in secondary syphilis for both HIV-positive and HIV-negative MSM nationally, suggesting interruption of syphilis progression.

Background The Trinity Biotech Uni-Gold HIV test (Uni-Gold) is often used as a supplementary rapid test in testing algorithms. Objective To evaluate the operational performance of the Uni-Gold as a first-line screening test among gay and bisexual men (GBM) in a setting where 4th generation HIV laboratory assays are routinely used. Study design We compared the performance of Uni-Gold with conventional HIV serology conducted in parallel among GBM attending 22 testing sites. Sensitivity was calculated separately for acute and established infection, defined using 4th generation screening Ag/Ab immunoassay (EIA) and Western blot results. Previous HIV testing history and results of supplementary 3rd generation HIV Ab EIA, and p24 antigen EIA were used to further characterise cases of acute infection. Results Of 10,793 specimens tested with Uni-Gold and conventional serology, 94 (0.90%, 95%CI:0.70–1.07) were confirmed as HIV-positive by conventional serology, and 37 (39.4%) were classified as acute infection. Uni-Gold sensitivity was 81.9% overall (77/94, 95%CI:72.6–89.1); 56.8% for acute infection (21/37, 95%CI:39.5–72.9) and 98.2% for established infection (56/57, 95%CI:90.6–100.0). Of 17 false non-reactive Uni-Gold results, 16 were acute infections, and of these seven were p24 antigen reactive but antibody negative. Uni-Gold specificity was 99.9% (10,692/10,699, 95%CI:99.9–100.0), PPV was 91.7% (95%CI:83.6–96.6) and NPV was 99.8% (95%CI:99.7–99.9), respectively. Conclusions In this population, Uni-Gold had good specificity and sensitivity was high for established infections when compared to 4th generation laboratory assays, however sensitivity was lower in acute infections. Where rapid tests are used in populations with a high proportion of acute infections, additional testing strategies are needed to detect acute infections.

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalised populations, particularly people who inject drugs (PWID), have low testing, linkage-to-care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: 1) review the evidence on MoCs for HCV; and 2) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring.

Introduction and designs Take-home naloxone (THN) interventions are an effective response to preventing overdose deaths, however uptake across Australia remains limited. This project designed, implemented and evaluated a model of care targeting opioid users attending alcohol and other drug (AOD) treatment, needle and syringe programs (NSP) and related health services targeting people who inject drugs. Design and methods Service providers, consumers and regulators collaboratively designed a THN brief intervention (ORTHN, Overdose Response with Take-Home Naloxone) involving client education and supply of naloxone in pre-filled syringes, delivered by nursing, allied health and NSP workers. ORTHN interventions were implemented in over 15 services across New South Wales, Australia. The evaluation included client knowledge, attitudes, substance use and overdose experiences immediately before and 3 months after ORTHN intervention in a subsample of participants. Results Six hundred and sixteen interventions were delivered, with 145 participants recruited to the research subsample, of whom 95 completed the three-month follow up. Overdose-related attitudes amongst participants improved following ORTHN, with no evidence of increased substance use or failure to implement other 'first responses' (e.g. calling an ambulance). Nine participants (10%) reversed an overdose using THN in the follow-up period. Participants identified a willingness to access THN from a range of services. While a minority (16%) indicated they were unwilling to pay for THN, the median price that participants were willing to pay was $AUD20 (IQR $10.40). Discussion and conclusions The ORTHN model of care for THN appears an effective way to disseminate THN to people who use opioids attending AOD, NSP and related health-care settings.

Background Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. Methods The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Results Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94). Conclusions High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. Clinical Trials Registration NCT02102451.

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.

Objectives To estimate rates of HIV infection, chlamydia, gonorrhoea, and infectious syphilis in transgender men and women in Australia; to compare these rates with those for cisgender people. Design Cross-sectional, comparative analysis of de-identified health data. Setting, participants We analysed data for 1260 transgender people (404 men, 492 women, 364 unrecorded gender), 78 108 cisgender gay and bisexual men, and 309 740 cisgender heterosexual people who attended 46 sexual health clinics across Australia during 2010-2017. Main outcome measures First-visit test positivity for sexually transmitted infections (STIs), stratified by patient group and year; demographic and behavioural factors associated with having STIs. Results 14 of 233 transgender men (6.0%) and 34 of 326 transgender women (10%) tested during first clinic visits were chlamydia-positive; nine transgender men (4%) and 28 transgender women (8.6%) were gonorrhoea-positive. One of 210 tested transgender men (0.5%) and ten of 324 tested transgender women (3.1%) were diagnosed with infectious syphilis; 14 transgender men (3.5%) and 28 transgender women (5.7%) were HIV-positive at their first visit. The only significant change in prevalence of an STI among transgender patients during the study period was the increased rate of gonorrhoea among transgender women (from 3.1% to 9.8%). Compared with cisgender gay and bisexual men, transgender men were less likely (adjusted odds ratio [aOR], 0.46; 95% CI, 0.29-0.71; P = 0.001) and transgender women as likely (aOR, 0.98; 95% CI, 0.73-1.32; P = 0.92) to be diagnosed with a bacterial STI; compared with heterosexual patients, transgender men were as likely (aOR, 0.72; 95% CI, 0.46-1.13; P = 0.16) and transgender women more likely (aOR, 1.56; 95% CI, 1.16-2.10; P = 0.003) to receive a first-visit bacterial STI diagnosis. Conclusions The epidemiology of STIs in transgender people attending Australian sexual health clinics differs from that of cisgender patients. Gender details must be captured by health data systems to facilitate appropriate delivery of sexual health care.