Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

INTRODUCTION: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. METHODS: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. RESULTS: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. CONCLUSIONS: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

Controlling COVID-19 outbreaks in the correctional setting: A mathematical modelling study.

Correctional centres (termed here 'prisons') are at high risk of COVID-19 and have featured major outbreaks worldwide. Inevitable close contacts, frequent inmate movements, and a disproportionate burden of co-morbidities mean these environments need to be prioritised in any public health response to respiratory pathogens such as COVID-19. We developed an individual-based SARS-CoV-2 transmission model for the prison system in New South Wales, Australia - incorporating all 33 correctional centres, 13,458 inmates, 578 healthcare and 6,909 custodial staff. Potential COVID-19 disease outbreaks were assessed under various mitigation strategies, including quarantine on entry, isolation of cases, rapid antigen testing of staff, as well as immunisation.Without control measures, the model projected a peak of 472 new infections daily by day 35 across the prison system, with all inmates infected by day 120. The most effective individual mitigation strategies were high immunisation coverage and prompt lockdown of centres with infected inmates which reduced outbreak size by 62-73%. Other than immunisation, the combination of quarantine of inmates at entry, isolation of proven or suspected cases, and widespread use of personal protective equipment by staff and inmates was the most effective strategy. High immunisation coverage mitigates the spread of COVID-19 within and between correctional settings but is insufficient alone. Maintaining quarantine and isolation, along with high immunisation levels, will allow correctional systems to function with a low risk of outbreaks. These results have informed public health policy for respiratory pathogens in Australian correctional systems.

Preparing correctional settings for the next pandemic: a modeling study of COVID-19 outbreaks in two high-income countries.

Introduction: Correctional facilities are high-priority settings for coordinated public health responses to the COVID-19 pandemic. These facilities are at high risk of disease transmission due to close contacts between people in prison and with the wider community. People in prison are also vulnerable to severe disease given their high burden of co-morbidities. Methods: We developed a mathematical model to evaluate the effect of various public health interventions, including vaccination, on the mitigation of COVID-19 outbreaks, applying it to prisons in Australia and Canada. Results: We found that, in the absence of any intervention, an outbreak would occur and infect almost 100% of people in prison within 20 days of the index case. However, the rapid rollout of vaccines with other non-pharmaceutical interventions would almost eliminate the risk of an outbreak. Discussion: Our study highlights that high vaccination coverage is required for variants with high transmission probability to completely mitigate the outbreak risk in prisons.

Scale-up of Direct-Acting Antiviral Treatment in Prisons Is Both Cost-effective and Key to Hepatitis C Virus Elimination.

Background: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings. Methods: A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021-2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021-2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed. Results: Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community. Conclusions: Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy. Clinical Trials Registration: NCT02064049.

Optimizing point-of-care testing strategies for diagnosis and treatment of hepatitis C virus infection in Australia: a model-based cost-effectiveness analysis.

Background: Timely diagnosis and treatment of hepatitis C virus (HCV) is critical to achieve elimination goals. This study evaluated the cost-effectiveness of point-of-care testing strategies for HCV compared to laboratory-based testing in standard-of-care. Methods: Cost-effectiveness analyses were undertaken from the perspective of Australian Governments as funders by modelling point-of-care testing strategies compared to standard-of-care in needle and syringe programs, drug treatment clinics, and prisons. Point-of-care testing strategies included immediate point-of-care HCV RNA testing and combined point-of-care HCV antibody and reflex RNA testing for HCV antibody positive people (with and without consideration of previous treatment). Sensitivity analyses were performed to investigate the cost per treatment initiation with different testing strategies at different HCV antibody prevalence levels. Findings: The average costs per HCV treatment initiation by point-of-care testing, from A$890 to A$1406, were up to 35% lower compared to standard-of-care ranging from A$1248 to A$1632 depending on settings. The average costs per treatment initiation by point-of-care testing for three settings ranged from A$1080 to A$1406 for RNA, A$960-A$1310 for combined antibody/RNA without treatment history consideration, and A$890-A$1189 for combined antibody/RNA with treatment history consideration. When HCV antibody prevalence was <74%, combined point-of-care HCV antibody and point-of-care RNA testing were the most cost-effective strategies. Modest increases in treatment uptake by 8%-31% were required for immediate point-of-care HCV RNA testing to achieve equivalent cost per treatment initiation compared to standard-of-care. Interpretation: Point-of-care testing is more cost-effective than standard of care for populations at risk of HCV. Testing strategies combining point-of-care HCV antibody and RNA testing are likely to be cost-effective in most settings. Funding: National Health and Medical Research Council.

Removing hepatitis C antibody testing for Australian blood donations: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted hepatitis C virus (HCV) infections is extremely low in Australia. This study aims to conduct a cost-effectiveness analysis of different testing strategies for HCV infection in blood donations. MATERIALS AND METHODS: The four testing strategies evaluated in this study were universal testing with both HCV antibody (anti-HCV) and nucleic acid testing (NAT); anti-HCV and NAT for first-time donations and NAT only for repeat donations; anti-HCV and NAT for transfusible component donations and NAT only for plasma for further manufacture; and universal testing with NAT only. A decision-analytical model was developed to assess the cost-effectiveness of alternative HCV testing strategies. Sensitivity analysis and threshold analysis were conducted to account for data uncertainty. RESULTS: The number of potential transfusion-transmitted cases of acute hepatitis C and chronic hepatitis C was approximately zero in all four strategies. Universal testing with NAT only was the most cost-effective strategy due to the lowest testing cost. The threshold analysis showed that for the current practice to be cost-effective, the residual risks of other testing strategies would have to be at least 1 HCV infection in 2424 donations, which is over 60,000 times the baseline residual risk (1 in 151 million donations). CONCLUSION: The screening strategy for HCV in blood donations currently implemented in Australia is not cost-effective compared with targeted testing or universal testing with NAT only. Partial or total removal of anti-HCV testing would bring significant cost savings without compromising blood recipient safety.

Australia could miss the WHO hepatitis C virus elimination targets due to declining treatment uptake and ongoing burden of advanced liver disease complications.

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

Hepatitis C treatment strategies in prisons: A cost-effectiveness analysis.

In Australian prisons approximately 20% of inmates are chronically infected with hepatitis C virus (HCV), providing an important population for targeted treatment and prevention. A dynamic mathematical model of HCV transmission was used to assess the impact of increasing direct-acting antiviral (DAA) treatment uptake on HCV incidence and prevalence in the prisons in New South Wales, Australia, and to assess the cost-effectiveness of alternate treatment strategies. We developed four separate models reflecting different average prison lengths of stay (LOS) of 2, 6, 24, and 36 months. Each model considered four DAA treatment coverage scenarios of 10% (status-quo), 25%, 50%, and 90% over 2016-2045. For each model and scenario, we estimated the lifetime burden of disease, costs and changes in quality-adjusted life years (QALYs) in prison and in the community during 2016-2075. Costs and QALYs were discounted 3.5% annually and adjusted to 2015 Australian dollars. Compared to treating 10% of infected prisoners, increasing DAA coverage to 25%, 50%, and 90% reduced HCV incidence in prisons by 9-33% (2-months LOS), 26-65% (6-months LOS), 37-70% (24-months LOS), and 35-65% (36-months LOS). DAA treatment was highly cost-effective among all LOS models at conservative willingness-to-pay thresholds. DAA therapy became increasingly cost-effective with increasing coverage. Compared to 10% treatment coverage, the incremental cost per QALY ranged from $497-$569 (2-months LOS), -$280-$323 (6-months LOS), -$432-$426 (24-months LOS), and -$245-$477 (36-months LOS). Treating more than 25% of HCV-infected prisoners with DAA therapy is highly cost-effective. This study shows that treating HCV-infected prisoners is highly cost-effective and should be a government priority for the global HCV elimination effort.

Assessment of Treatment Strategies to Achieve Hepatitis C Elimination in Canada Using a Validated Model.

Importance: Achievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy. Objective: To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030. Design, Setting, and Participants: Study participants in this decision analytical model included individuals with hepatitis C virus infection in Canada. Five HCV treatment scenarios (optimistic, very aggressive, aggressive, gradual decrease, and rapid decrease) were applied using a previously validated Markov-type mathematical model. The optimistic and very aggressive treatment scenarios modeled a sustained annual treatment of 10 200 persons and 14 000 persons, respectively, from 2018 to 2030. The aggressive, gradual decrease, and rapid decrease scenarios assessed decreases in treatment uptake from 14 000 persons to 10 000 persons per year, 12 000 persons to 8500 persons per year, and 12 000 persons to 4500 persons per year, respectively, between 2018 and 2030. Main Outcomes and Measures: Hepatitis C virus prevalence and HCV-associated health outcomes were assessed for each of the 5 treatment scenarios with the goal of identifying strategies to achieve HCV elimination by 2030. Results: An estimated mean 180 142 persons (95% CI, 122 786-196 862 persons) in Canada had chronic HCV infection at the end of 2017. The optimistic and gradual decrease scenarios estimated a decrease in HCV prevalence from 180 142 persons to 37 246 persons and 37 721 persons, respectively, by 2030. Relative to 2015, this decrease in HCV prevalence was associated with 74%, 69%, and 69% reductions in the prevalence of decompensated cirrhosis, hepatocellular carcinoma, and liver-associated mortality, respectively, leading to HCV elimination by 2030. More aggressive treatment uptake (very aggressive scenario) could result in goal achievement up to 3 years earlier than 2030, although a rapid decrease in the initiation of treatment (rapid decrease scenario) would preclude Canada from reaching the HCV elimination goal by 2030. Conclusions and Relevance: The study findings suggest that Canada could meet the WHO goals for HCV elimination by 2030 by sustaining the current national HCV treatment rate during the next decade. This target will not be achieved if treatment uptake is allowed to decrease rapidly.

Estimating the number of people who inject drugs and syringe coverage in Australia, 2005-2016.

BACKGROUND: Effective targeting of harm reduction programs for people who inject drugs (PWID) requires timely and robust estimates of the size of this population. This study estimated the number of people who inject drugs on a regular basis in Australia, calculated syringe coverage per person and the proportion of their injections covered by a sterile needle and syringe. METHODS: We used trends in indicators of injection drug use to extend the 2005 estimate of the population of people who regularly inject drugs from 2005 to 2016. Included indicators were lifetime/recent injection of illicit drugs, drug-related arrests, drug-related seizures, accidental deaths due to opioids, opioid-related hospital admissions/separations and new diagnoses of hepatitis C virus infection among those aged 15-24 years. Syringe distribution and frequency of injection data were used to assess syringe coverage per PWID and the proportion of their injections covered by a sterile syringe. RESULTS: The estimated number of people who regularly inject drugs in Australia increased by 7%, from 72,000 in 2005 to 77,270 in 2016. The annual number of syringes distributed per person increased 34%, from 470 syringes in 2005 to 640 syringes in 2016. Syringe coverage per injection first exceeded 100% in Australia in 2013. CONCLUSIONS: Despite Australia's high syringe coverage by international standards, the number of syringes distributed is likely to be only narrowly meeting demand. It is critical that needle syringe programs be provided with sufficient resources to continue their role as the key intervention required to prevent HIV and HCV transmission among PWID.

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

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

Estimating the cost-effectiveness of needle-syringe programs in Australia.

OBJECTIVE: To evaluate the impact and cost-effectiveness of needle-syringe programs (NSPs) with respect to HIV and hepatitis C virus (HCV) infections among Australian injecting drug users (IDUs). DESIGN/METHODS: A health economic analysis was conducted incorporating a mathematical model of HIV and HCV transmission among IDUs. An empirical relationship between syringe availability and receptive syringe sharing (RSS) was assessed. We compared the epidemiological outcomes and costs of NSP coverage (status quo RSS of 15-17%) with scenarios that had no NSPs (RSS of 25-50%). Outcomes included numbers of HIV and HCV infections averted, lifetime health sector costs, and cost per quality-adjusted life year (QALY) gained. Discounting was applied at 3% (sensitivity: 0%, 5%) per annum. RESULTS: We estimated that NSPs reduced incidence of HIV by 34-70% (192-873 cases) and HCV by 15-43% (19 000-77 000 cases) during 2000-2010, leading to 20 000-66 000 QALYs gained. Economic analysis showed that NSP coverage saved A$70-220 million in healthcare costs during 2000-2010 and will save an additional A$340-950 million in future healthcare costs. With NSPs costing A$245 million, the programs are very cost-effective at A$416-8750 per QALY gained. Financial investment in NSPs over 2000-2010 is estimated to be entirely recovered in healthcare cost savings by 2032 with a total future return on investment of $1.3-5.5 for every $1 invested. CONCLUSION: Australia's early introduction and high coverage of NSPs has significantly reduced the prevalence of HIV and HCV among IDUs. NSPs are a cost-effective public health strategy and will result in substantial net cost savings in the future.

What impact might the economic crisis have on HIV epidemics in Southeast Asia?

OBJECTIVE: To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. DESIGN: To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an expansion phase. METHODS: Major HIV-related risk factors that may change due to the GEC were identified and a dynamic mathematical transmission model was developed and used to forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3 years. RESULTS: In Cambodia, the total numbers of HIV diagnoses are not expected to be largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due to potential changes in behavior, may not be observed by the surveillance system. In PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education programs are the factors that may be of greatest concern in both settings. A reduction in the rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to 7.5% after 3 years). CONCLUSIONS: The GEC is likely to have a modest impact on HIV epidemics. However, there are plausible conditions under which the economic downturns can noticeably influence epidemic trends. This study highlights the high importance of maintaining funding for HIV programs.

The impact of needle and syringe programs on HIV and HCV transmissions in injecting drug users in Australia: a model-based analysis.

OBJECTIVES: We aim to estimate how changes in sterile syringe distribution through needle-syringe programs (NSPs) may affect HIV and hepatitis C virus (HCV) incidence among injecting drug users (IDUs) in Australia. METHODS: We develop a novel mathematical model of HIV and HCV transmission among IDUs who share syringes. It is calibrated using biological and Australian epidemiological and behavioral data. Assuming NSP syringe distribution affects the number of times each syringe is used before disposal, we use the model to estimate the relationship between incidence and syringe distribution. RESULTS: HIV is effectively controlled through NSP distribution of sterile syringes {with the effective reproduction ratio below 1 [0.66 median, interquartile range (0.63-0.70)] under current syringe distribution}. In contrast, HCV incidence is expected to remain high and its control is not feasible in the foreseeable future. The proportion of injections that are shared and the number of times each syringe is used before disposal are the driving factors of HCV incidence. The frequency in which each syringe is used can potentially be influenced by changes in syringe distribution. We estimate that if syringe distribution or coverage doubled, then annual incidence is likely to reduce by 50%. However, if it was decreased to one third of the current level, then approximately 3 times the incidence could be expected. CONCLUSIONS: This research highlights the large benefits of NSPs, puts forward a quantitative relationship between incidence and syringe distribution, and indicates that increased coverage could result in significant reductions in viral transmissions among IDUs.