Cost evaluation of continuation of therapy with dalbavancin compared to standard-of-care antibiotics alone in hospitalized persons who inject drugs with severe gram-positive infections.

PURPOSE: Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. METHODS: This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. RESULTS: A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). CONCLUSION: DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.

The potential for medicinal cannabis to help manage challenging behaviour in people with intellectual disability: A perspective review.

BACKGROUND: Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with 'challenging behaviour', which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns. This predisposes to poor health and social outcomes. There is no evidence-based treatments for managing challenging behaviour. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are being trialled for a range of disorders, which are over-represented in PwID and provoke challenging behaviours, such as severe epilepsy, spasticity, post-traumatic stress disorder, social phobia, pain, etc. METHODS: This perspective review explores the different conditions, which benefit from medicinal CBD/THC preparations, by analysing recent literature from neurobiological, pre-clinical and clinical studies related to the topic. The evidence is synthesised to build an argument of the therapeutic benefits and challenges of medicinal cannabis to manage severe challenging behaviour in PwID. RESULTS: There is developing evidence of medicinal CBD/THC improving psychiatric and behavioural presentations in general. In particular, there is emergent proof in certain key areas of influence of medicinal CBD/THC positively supporting challenging behaviour, for example in children with neurodevelopmental disorders. However, there are significant challenges in employing such treatments in vulnerable populations such as PwID. CONCLUSION: Further clinical research for the considered use of medicinal CBD/THC for challenging behaviour management in PwID is needed. Strong co-production with experts with lived experience is needed for further testing to be done in this exciting new area.

Modeling the Health Economic Burden of Hepatitis C Virus Infection in Turkey: Cost-Effectiveness of Targeted Screening.

BACKGROUND/AIMS: In 2016, World Health Organization introduced global goals to eliminate hepatitis C virus by 2030. The aim of this study is to analyze the epidemiologic and economic burden of hepatitis C virus in Turkey and compare current practice (regular care) with a hypothetical active screening and treatment approach (active scenario). MATERIALS AND METHODS: A Markov model was used to analyze and compare regular care with a scenario developed by experts including the screening and treatment of all acute and chronic hepatitis C virus infections between 2020 and 2050. General and targeted populations were focused. The model reflected the natural history of the disease, and the inputs were based on a literature review and expert opinions. Costs were provided by previous studies and national regulations. RESULTS: The active scenario resulted in higher spending for all groups compared with regular care in the first year. Cumulative costs were equalized in the 8th, 12th, 13th, and 16th year and followed by cost-savings of 49.7 million, 1.1 billion, 288.6 million, and 883.4 million Turkish liras in 20 years for prisoners, refugees, people who inject drugs (PWID), and all population, respectively. In all groups, the mortality was found to be lower with the active scenario. In total, 62.8% and 50.6% of expected deaths with regular care in 5 and 20 years, respectively, were prevented with the active scenario. CONCLUSIONS: An active screening and treatment approach for hepatitis C virus infection could be cost-effective for PWID, prisoners, and refugees. Almost two-thirds of deaths in regular care could be prevented in 5 years' time with this approach.

"Apparently, you can only be treated once": A qualitative study exploring perceptions of hepatitis C and access to treatment among people who inject drugs visiting a needle and syringe program.

BACKGROUND: Access to hepatitis C care within harm reduction community organizations for people who inject drugs is crucial for achieving hepatitis C elimination. However, there is a lack of data on how perceptions of hepatitis C and treatment have changed among individuals visiting these organizations during the era of direct-acting antivirals (DAAs). This study aimed to explore the perceptions of hepatitis C and treatment access for (re)infection among individuals visiting a needle and syringe program in Canada. METHODS: Eighteen semi-structured interviews were conducted with individuals who recently injected drugs and visited a needle and syringe program. The interviews were guided by the Common-Sense Self-Regulation Model (CS-SRM) and aimed to explore cognitive and emotional representations of hepatitis C, perceptions of treatment, coping strategies and sources of information. Interviews were audio recorded, transcribed, and coded using thematic analysis. RESULTS: Most of the participants identified as male, were of white ethnicity and had a median age of 45. While most underscored the therapeutic advancements and the effectiveness of DAAs, they expressed confusion regarding the mechanisms of access to treatment, especially in cases of reinfection. Perceptions of the controllability of hepatitis C were significantly influenced by the stigmatizing discourse surrounding treatment access, cost, and public coverage. This influence extended to their intentions for seeking treatment. Participants emphasized the social consequences of hepatitis C, including stigma. Emotional representations of hepatitis C evolved along the care cascade, encompassing initial shock at diagnosis and later fear of reinfection following successful treatment. CONCLUSION: Nearly a decade after the advent of DAAs, misinformation about treatment access persists. Findings underscore a nexus of internalized and institutionalized stigma associated with hepatitis C, drug use, and the challenges of cost and access to treatment, pointing to a clear need for education and service delivery optimisation in harm reduction community organizations.

Cost-effectiveness of integrated treatment for hepatitis C virus (HCV) among people who inject drugs in Norway: An economic evaluation of the INTRO-HCV trial.

BACKGROUND AND AIMS: The INTRO-HCV randomized controlled trial conducted in Norway over 2017-2019 found that integrated treatment, compared with standard-of-care hospital treatment, for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost-effectiveness of the INTRO-HCV intervention. DESIGN: A Markov health state transition model of HCV disease progression and treatment with cost-effectiveness analysis from the health-provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality-adjusted life-years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia). SETTING AND PARTICIPANTS: PWID attending community-based drug treatment centers for people with opioid dependence in Norway. MEASUREMENTS: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness-to-pay threshold for Norway and lower (€20 000/QALY) threshold common among high-income countries. FINDINGS: Integrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost-effective against conventional and lower willingness-to-pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost-effective at the lower willingness-to-pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost-saving, respectively. Sensitivity analyses suggest integrated treatment was cost-effective at the lower willingness-to-pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost-saving with 60%-90% price reductions. CONCLUSIONS: Integrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost-effective compared with standard-of-care referral pathways in Norway and may be cost-saving in settings with particular characteristics.

Assessment of Tennessee's county-level vulnerability to hepatitis C virus and HIV outbreaks using socioeconomic, healthcare, and substance use indicators.

BACKGROUND: Human immunodeficiency virus (HIV), hepatitis C virus (HCV), and injection drug use are syndemic in the central Appalachian states. In Tennessee (TN), declines in HIV among persons who inject drugs (PWID) stalled, and HCV infection rates increased significantly from 2013-2017. To better target strategies to address the syndemic, county-level socioeconomic, opioid use, access to healthcare, and health factors were modeled to identify indicators predictive of vulnerability to an HIV/HCV outbreak among PWID in TN. METHODS: Newly reported chronic HCV cases among persons aged 13-39 years in 2016-2017 were used as a proxy for county-level HIV/HCV vulnerability among TN's 95 counties. Seventy-five publicly available county-level measures from 2016-2017 were collected and reduced through multiple dimension reduction techniques. Negative binomial regression identified indicators associated with HCV which were used to calculate county-level vulnerability to a local HIV/HCV outbreak. RESULTS: Thirteen county-level indicators were identified as strongly predictive of HIV/HCV vulnerability with the statistically significant indicators being percentage of the population aged 20-44 years, per capita income, teen birth rate, percentage of clients in TDMHSAS-funded opioid treatment and recovery, syphilis case rate, and percentage of homes with at least one vehicle. Based on the 13 indicators, we identified the distribution of vulnerability to an HIV/HCV outbreak among TN's counties. Eleven high vulnerability counties were identified, with the preponderance located in east and middle TN. CONCLUSION: This analysis identified the county-level factors most associated with vulnerability to an HIV/HCV outbreak among PWID in TN. These results, alongside routine surveillance, will guide targeted prevention and linkage to care efforts for the most vulnerable communities.

Hepatitis C incidence among patients attending primary care health services that specialise in the care of people who inject drugs, Victoria, Australia, 2009 to 2020.

BACKGROUND: Monitoring trends in hepatitis C virus (HCV) incidence is critical for evaluating strategies aimed at eliminating HCV as a public health threat. We estimate HCV incidence and assess trends in incidence over time among primary care patients. METHODS: Data were routinely extracted, linked electronic medical records from 12 primary care health services. Patients included were aged ≥16 years, tested HCV antibody negative on their first test recorded and had at least one subsequent HCV antibody or RNA test (January 2009-December 2020). HCV incident infections were defined as a positive HCV antibody or RNA test. A generalised linear model assessed the association between HCV incidence and calendar year. RESULTS: In total, 6711 patients contributed 17,098 HCV test records, 210 incident HCV infections and 19,566 person-years; incidence was 1.1 per 100 person-years (95% confidence interval (CI): 0.9 to 1.2). Among 559 (8.2%) patients ever prescribed opioid-related pharmacotherapy (ORP) during the observation period, 135 infections occurred during 2,082 person-years (incidence rate of 6.5 per 100 person-years (95% CI: 5.4 to 7.7)). HCV incidence declined 2009-2020 overall (incidence rate ratio per calendar year 0.8 (95% CI: 0.8 to 0.9) and among patients ever prescribed ORT (incidence rate ratio per calendar year 0.9, 95% CI: 0.75 to 1.0). CONCLUSION: HCV incidence declined among patients at primary care health services including among patients ever prescribed ORP and during the period following increased access to DAA therapy.

Assessment of an online calculator's vancomycin dosing and exposure appropriateness in persons who inject drugs with methicillin-resistant Staphylococcus aureus bloodstream infections.

WHAT IS KNOWN AND OBJECTIVE: While the gold standard for calculating AUC involves two steady-state concentrations, online calculators can empirically estimate AUC and other pharmacokinetic (PK) parameters. In patients with potentially altered PK, such as persons who inject drugs (PWID), the reliability of these predictions is unclear. Our objectives were to characterize the PK of vancomycin in PWID with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) and to assess the impact of these PK parameters on dosing regimens when compared to regimens generated by an online calculator. METHODS: This descriptive pilot study included a retrospective chart review of 48 inpatient PWID with MRSA BSI from 30 April 2018 through 31 August 2020. Demographic and clinical data along with vancomycin dosing and serum concentrations were collected. Patient-specific PK parameters were used to calculate the AUC of each empiric regimen compared with the originally predicted AUC. RESULTS AND DISCUSSION: The study population had a median volume of distribution of 0.74 L/kg, clearance of 0.081 L/kg/h, elimination rate constant of 0.110/h and half-life of 6.3 h. The online calculator empirically predicted 6 subtherapeutic and 42 appropriate AUC values with its recommended empiric dosing regimens. Using the actual patient-specific PK parameters, the empiric vancomycin regimens actually resulted in 21 (43.75%) underexposures, 24 (50%) appropriate exposures and 3 (6.25%) overexposures. WHAT IS NEW AND CONCLUSIONS: In PWID, empiric vancomycin dosing strategies suggested by an online calculator frequently resulted in lower-than-predicted vancomycin exposures. These findings suggest that PWID with MRSA BSI may require higher and/or more frequent vancomycin doses than those empirically recommended by the population-based methods of an online calculator.

Costs and impact on HIV transmission of a switch from a criminalisation to a public health approach to injecting drug use in eastern Europe and central Asia: a modelling analysis.

BACKGROUND: HIV incidence is increasing in eastern Europe and central Asia, primarily driven by injecting drug use. Coverage of antiretroviral therapy (ART) and opioid agonist therapy are suboptimal, with many people who inject drugs (PWID) being incarcerated. We aimed to assess whether use of monies saved as a result of decriminalisation of drug use or possession to scale up ART and opioid agonist therapy could control HIV transmission among PWID in eastern Europe and central Asia. METHODS: A dynamic HIV transmission model among PWID incorporating incarceration, ART, and opioid agonist therapy was calibrated to Belarus, Kazakhstan, Kyrgyzstan, and St Petersburg (Russia). Country-specific costs for opioid agonist therapy, ART, and incarceration were collated or estimated. Compared with baseline, the model prospectively projected the life-years gained, incremental costs (2018 euros), and infections prevented over 2020-40 for three scenarios. The decriminalisation scenario removed incarceration resulting from drug use or possession for personal use, reducing incarceration among PWID by 24·8% in Belarus, Kazakhstan, and Kyrgyzstan and 46·4% in St Petersburg; the public health approach scenario used savings from decriminalisation to scale up ART and opioid agonist therapy; and the full scale-up scenario included the decriminalisation scenario plus investment of additional resources to scale up ART to the UNAIDS 90-90-90 target of 81% coverage and opioid agonist therapy to the WHO target of 40% coverage. The incremental cost-effectiveness ratios per life-year gained for each scenario were calculated and compared with country-specific gross domestic product per-capita willingness-to-pay thresholds. Costs and life-years gained were discounted 3% annually. FINDINGS: Current levels of incarceration, opioid agonist therapy, and ART were estimated to cost from €198 million (95% credibility interval 173-224) in Kyrgyzstan to €4129 million (3897-4358) in Kazakhstan over 2020-40; 74·8-95·8% of these total costs were incarceration costs. Decriminalisation resulted in cost savings (€38-773 million due to reduced prison costs; 16·9-26·1% reduction in overall costs) but modest life-years gained (745-1694). The public health approach was cost saving, allowing each setting to reach 81% ART coverage and 29·7-41·8% coverage of opioid agonist therapy, resulting in 17 768-148 464 life-years gained and 58·9-83·7% of infections prevented. Results were similar for the full scale-up scenario. INTERPRETATION: Cost savings from decriminalisation of drug use could greatly reduce HIV transmission through increased coverage of opioid agonist therapy and ART among PWID in eastern Europe and central Asia. FUNDING: Alliance for Public Health, US National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse, and Economist Intelligence Unit.

Cost effectiveness of simplified HCV screening-and-treatment interventions for people who inject drugs in Dar-es-Salaam, Tanzania.

BACKGROUND: Compared to other countries in sub-Saharan Africa, Tanzania has a relatively progressive illicit drug harm reduction (HR) policy, through a predominantly opioid substitution therapy-based programme. However, access to hepatitis C virus (HCV) diagnosis and curative direct acting antiviral therapy remains elusive. We developed a cost-effectiveness model to evaluate a simplified HCV screening-and-treatment intervention amongst PWID in Dar-es-Salaam, Tanzania. METHODS: A decision tree and Markov state transition model compared existing practice (no access to HCV viral confirmation and treatment) with the integration of point-of-care HCV screening and treatment within (1) existing HR services and (2) expansion to include PWID not currently engaged in HR. Outcome measures were screening, treatment, HR and disease-related costs per PWID, quality-adjusted life years (QALY) and disability adjusted life years (DALY). Cost-effectiveness was evaluated from a healthcare payer's perspective over a 30-year time horizon over a range of willingness-to-pay thresholds (USD$273 to USD$1,050). Both deterministic and probabilistic sensitivity analyses have been conducted. RESULTS: Assuming a chronic HCV prevalence of 18.8%, screening-and-treatment in existing HR settings resulted in an ICER per QALY-gained and DALY averted of USD$633 and USD$1,161, respectively. Expanding to include an outreach programme for unengaged PWID yielded an ICER per QALY-gained and DALY-averted of USD$4,091 and USD$10,288. Factors affecting the sensitivity of the ICER value included the cost of HR and the health utility of non-cirrhotic disease states. CONCLUSION: Simplified HCV screening and treatment of PWID has the potential to be cost-effective in Dar-es-Salaam, Tanzania. In practice, synergism of human and financial resources with established health programmes may offer a pragmatic solution to minimise operational costs.

An intensive model of care for hepatitis C virus screening and treatment with direct-acting antivirals in people who inject drugs in Nairobi, Kenya: a model-based cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment is essential for eliminating HCV in people who inject drugs (PWID), but has limited coverage in resource-limited settings. We measured the cost-effectiveness of a pilot HCV screening and treatment intervention using directly observed therapy among PWID attending harm reduction services in Nairobi, Kenya. DESIGN: We utilized an existing model of HIV and HCV transmission among current and former PWID in Nairobi to estimate the cost-effectiveness of screening and treatment for HCV, including prevention benefits versus no screening and treatment. The cure rate of treatment and costs for screening and treatment were estimated from intervention data, while other model parameters were derived from literature. Cost-effectiveness was evaluated over a life-time horizon from the health-care provider's perspective. One-way and probabilistic sensitivity analyses were performed. SETTING: Nairobi, Kenya. POPULATION: PWID. MEASUREMENTS: Treatment costs, incremental cost-effectiveness ratio (cost per disability-adjusted life year averted). FINDINGS: The cost per disability-adjusted life-year averted for the intervention was $975, with 92.1% of the probabilistic sensitivity analyses simulations falling below the per capita gross domestic product for Kenya ($1509; commonly used as a suitable threshold for determining whether an intervention is cost-effective). However, the intervention was not cost-effective at the opportunity cost-based cost-effectiveness threshold of $647 per disability-adjusted life-year averted. Sensitivity analyses showed that the intervention could provide more value for money by including modelled estimates for HCV disease care costs, assuming lower drug prices ($75 instead of $728 per course) and excluding directly-observed therapy costs. CONCLUSIONS: The current strategy of screening and treatment for hepatitis C virus (HCV) among people who inject drugs in Nairobi is likely to be highly cost-effective with currently available cheaper drug prices, if directly-observed therapy is not used and HCV disease care costs are accounted for.

Cost-effectiveness of mass screening for Hepatitis C virus among all inmates in an Irish prison.

BACKGROUND: In Irish prisons, there is a high proportion of people who inject drugs (PWID; 26%) and a high prevalence of HCV (16%), making prison a high priority setting for HCV testing and treatment. We evaluate the cost-effectiveness of a mass HCV screening intervention in Mountjoy Prison, Dublin, compared to the standard-of-care of intermittent screening on committal. METHODS: Primary cost data was collected from the intervention using an overall provider perspective. Standard-of-care (SOC) costs were estimated through interview. All costs were inflated to 2020 Euros. An HCV transmission and disease progression model among incarcerated and community PWID and ex-injectors was calibrated to the Dublin HCV epidemic, allowing inclusion of population-level health benefits. The model used intervention data, suggesting 419 individuals were screened, 50 HCV infections diagnosed and 32 individuals initiated treatment, to project the resulting costs and health benefits (quality adjusted life years or QALYs) over 50 years with 5% discounting. The incremental cost effectiveness ratio (ICER), cost per QALY gained, was estimated for the screening intervention compared to the standard-of-care. Probabilistic sensitivity analyses (PSA) determined the probability that the intervention was cost-effective compared to a willingness-to-pay threshold of €30,000/QALY as used in Ireland. The ICER for 1- or 3-yearly mass screening in all Dublin prisons was also calculated. RESULTS: The total direct costs of the intervention (not including treatment drug costs) was €82,392, with most costs being due to staff (43%) and overhead or management costs (38%). Despite having little epidemiological impact due to the small numbers treated, over 50 years the incremental cost of the intervention was €36,592 and 3.8 QALYs were gained, giving a mean ICER of €9,552/QALY. The majority (84%) of PSA runs were below the willingness-to-pay threshold. Yearly mass screening had an ICER of €2,729/QALY compared to SOC and gave a higher net monetary benefit (€7,393,382) than screening every 3 years (€6,252,816). CONCLUSION: Prison mass screening could be a cost-effective initiative for increasing testing and treatment of HCV in Ireland.

"Stigma is where the harm comes from": Exploring expectations and lived experiences of hepatitis C virus post-treatment trajectories among people who inject drugs.

BACKGROUND: The advent of direct-acting antiviral (DAA) medications has facilitated opportunities to treat hepatitis C virus (HCV) among people who inject drugs (PWID). However, there remains a need for data about how to optimally support PWID throughout DAA post-treatment trajectories, including with regard to re-infection prevention. The objective of this study is therefore to identify how PWID with lived experience of HCV describe their expectations and experiences related to health and social outcomes, contexts, and substance use practices following completion of DAA treatment. METHODS: We thematically analyzed data from in-depth, semi-structured interviews, conducted between January and June 2018, in Vancouver, Canada, with a purposive sample (n = 50) of PWID at various stages of DAA treatment (e.g., pre, peri, post). RESULTS: Our analysis yielded three themes. First, while participants had hoped to experience holistic enhancements in wellbeing following HCV cure, discussions of actual post-treatment experiences tended to be located in physical health (e.g., increased energy). Second, participants often pointed to the ways in which HCV-related and other stigmas had restricted opportunities for health and healthcare access. Participants therefore identified stigma-reduction as a key motivator of HCV cure, and while reductions in internalized stigma were sometimes achieved, participants underscored that other forms of enacted stigma (e.g., related to: substance use, HIV, poverty) had continued to feature prominently in their post-treatment lives. Third, participants described considerable knowledge about how to prevent HCV re-infection following cure, but they also expressed apprehensiveness about how socio-structural barriers, including stigma and criminalization, could interfere with harm reduction and re-infection prevention efforts. CONCLUSIONS: DAAs are transforming the health and wellbeing of some PWID. Yet, HCV-related policy must extend beyond the scale-up of DAAs to include concerted public health investments, including anti-stigma efforts and improvements to the social welfare system, to meaningfully advance equity in PWID's post-treatment trajectories and outcomes.

Cost-effectiveness of hepatitis C virus (HCV) elimination strategies among people who inject drugs (PWID) in Tijuana, Mexico.

BACKGROUND AND AIMS: In Latin America, Mexico was first to launch a hepatitis C virus (HCV) elimination strategy, where people who inject drugs (PWID) are a main risk group for transmission. In Tijuana, HCV seroprevalence among PWID is > 90%, with minimal harm reduction (HR). We evaluated cost-effectiveness of strategies to achieve the incidence elimination target among PWID in Tijuana. METHODS: Modeling study using a dynamic, cost-effectiveness model of HCV transmission and progression among active and former PWID in Tijuana, to assess the cost-effectiveness of incidence elimination strategies from a health-care provider perspective. The model incorporated PWID transitions between HR stages (no HR, only opioid agonist therapy, only high coverage needle-syringe programs, both). Four strategies that could achieve the incidence target (80% reduction by 2030) were compared with the status quo (no intervention). The strategies incorporated the number of direct-acting anti-viral (DAA) treatments required with: (1) no HR scale-up, (2) HR scale-up from 2019 to 20% coverage among PWID, (3) HR to 40% coverage and (4) HR to 50% coverage. Costs (2019 US$) and health outcomes [disability-adjusted life years (DALYs)] were discounted 3% per year. Mean incremental cost-effectiveness ratios (ICER, $/DALY averted) were compared with one-time per capita gross domestic product (GDP) ($9698 in 2019) and purchasing power parity-adjusted per capita GDP ($4842-13 557) willingness-to-pay (WTP) thresholds. RESULTS: DAAs alone were the least costly elimination strategy [$173 million, 95% confidence interval (CI) = 126-238 million], but accrued fewer health benefits compared with strategies with HR. DAAs + 50% HR coverage among PWID averted the most DALYs but cost $265 million, 95% CI = 210-335 million). The optimal strategy was DAAs + 50% HR (ICER $6743/DALY averted compared to DAAs only) under the one-time per-capita GDP WTP ($9698). CONCLUSIONS: A combination of high-coverage harm reduction and hepatitis C virus treatment is the optimal cost-effective strategy to achieve the HCV incidence elimination goal in Mexico.

Assessment of PrEP Awareness, PrEP Discussion with a Provider, and PrEP Use by Transmission Risk Group with an Emphasis on the Southern United States.

The number of new HIV diagnoses is highest in the South. Many persons who might benefit from pre-exposure prophylaxis (PrEP) are not engaged in the HIV PrEP continuum of care. We analyzed National HIV Behavioral Surveillance data to assess engagement in the PrEP continuum of care among persons with increased HIV risk. We compared PrEP awareness, discussion with a clinical provider, and use among persons living in the South to those living elsewhere in the United States. PrEP awareness was lowest among heterosexual persons (7%), highest among men who have sex with men (85%), and 26% among persons who inject drugs. PrEP use was low among each population (≤ 35% for all cycles). There was limited evidence of differences in PrEP use between persons in southern and non-southern U.S. Efforts are needed to increase use of PrEP among each of the groups with increased HIV risk.

RESUMEN: El número de nuevos diagnósticos de virus de la inmunodeficiencia humana (VIH) es más alto en el sur. Muchas personas que podrían beneficiarse de la profilaxis preexposición (PrEP) no participan en la VIH-PrEP continuidad de la atención. Analizamos datos del Sistema Nacional de Vigilancia del Comportamiento Relacionado con el VIH (conocido en inglés como National HIV Behavioral Surveillance System) para evaluar la participación en la PrEP continuidad de la atención en personas con mayor riesgo de contraer el VIH. Comparamos concientización de PrEP, discusión con un proveedor clínico, y uso entre personas que viven en el sur con las personas que viven en otras partes de los Estados Unidos. Concientización de PrEP fue más baja entre personas heterosexuales (7%), más alta entre hombres que tienen relaciones sexuales con hombres (91%), y 26% entre personas que se inyectan drogas. Utilización de PrEP fue baja para todas las poblaciones (≤35% para todos los ciclos). La evidencia de diferencias en el uso de PrEP entre personas que viven en el sur con personas que no viven en el sur de los Estados Unidos fue limitada. Se necesitan esfuerzos para aumentar el uso de PrEP entre estos grupos con más riesgo de contraer el VIH.

Upscaling prevention, testing and treatment to control hepatitis C as a public health threat in Dar es Salaam, Tanzania: A cost-effectiveness model.

BACKGROUND: Hepatitis C (HCV) elimination strategies are required for low and middle-income countries (LMICs), because although treatment access is currently limited, this is unlikely to remain the case forever. We estimate and compare the impact, cost and cost-effectiveness of a variety of prevent, test and treat strategies for HCV in Dar es Salaam, Tanzania. METHODS: A mathematical model. RESULTS: Without intervention, the HCV epidemic in Dar es Salaam was estimated to result in US$29.1 million in disease costs between 2018 and 2030. Maintaining existing harm reduction coverage (4% needle and syringe program, 42% opioid substitution therapy) over this period was estimated to prevent 22% of injecting drug use-acquired HCV infections compared to a zero coverage scenario. Implementing antibody/RNA, serum-based HCV core antigen (HCVcAg) and dry blood spot (DBS) HCVcAg test/treat programs among PWID increased the total cost by US$0.7 million, US$3.1 million and US$6.5 million respectively by 2030; however this expenditure led to 57%, 61% and 73% reductions in annual incidence among PWID, 25%, 27% and 33% reductions overall annual incidence (PWID+non-PWID), and reduced HCV prevalence among PWID from 27% to 9%, 8% and 5%, respectively. The Ab/RNA, serum-based and DBS HCVcAg test/treat programs cost US$689, US$2857 and US$5400 per disability-adjusted life year averted, respectively, compared to no test/treat program. CONCLUSION: Primary prevention among PWID can provide important reductions in HCV transmission in the absence of treatment availability. HCV Ab/RNA or serum-based HCVcAg test/treat programs among PWID are likely to be cost-effective in Dar es Salaam, with serum-based HCVcAg test/treat achieving greater impact due to a simpler diagnostic process and better retention in care. If used for regular testing of PWID, the additional coverage benefits of non-laboratory-based DBS HCVcAg tests in LMICs would outweigh their reduced sensitivity.

A cost-effectiveness analysis of primary versus hospital-based specialist care for direct acting antiviral hepatitis C treatment.

BACKGROUND: Hepatitis C virus elimination may be possible by scaling up direct-acting antiviral (DAA) treatment. Due to the safety and simplicity of DAA treatment, primary care-based treatment delivery is now feasible, efficacious and may be cheaper than hospital-based specialist care. In this paper, we use Prime Study data - a randomised controlled trial comparing the uptake of DAA treatment between primary and hospital-based care settings amongst people who inject drugs (PWID) - to estimate the cost of initiating treatment for PWID diagnosed with hepatitis C in primary care compared to hospital-based care. METHODS: The total economic costs associated with delivering DAA treatment (post hepatitis C diagnosis) within the Prime study - including health provider time/training, medical tests, equipment, logistics and pharmacy costs - were collected. Appointment data were used to estimate the number/type of appointments required to initiate treatment in each case, or the stage at which loss to follow up occurred. RESULTS: Among the hepatitis C patients randomised to be treated within primary care, 43/57 (75%) commenced treatment at a mean cost of A$885 (95% CI: A$850-938) per patient initiating treatment. In hospital-based care, 18/53 hepatitis C patients (34%) commenced treatment at a mean cost of A$2078 (range: A$2052-2394) per patient initiating treatment - more than twice as high as primary care. The lower cost in the primary care arm was predominantly the result of increased retention in care compared to the hospital-based arm. CONCLUSIONS: Compared to hospital-based care, providing hepatitis C services for PWID in primary care can improve treatment uptake and approximately halve the average cost of treatment initiation. To improve treatment uptake and cure, countries should consider primary care as the main model for hepatitis C treatment scale-up.

Understanding disparities in access to naloxone among people who inject drugs in Southeast Michigan using respondent driven sampling.

BACKGROUND: Given the rising incidence of opioid overdose in the United States, naloxone access is critical for high-risk populations, such as persons who inject drugs (PWID). Yet not all PWID have access to this life-saving antidote. With PWID in Michigan recruited via respondent driven sampling in 2017, after the 2016 standing order expanding naloxone availability through local pharmacies, we explored possible access disparities. METHODS: With 46 seeds recruited from agencies serving local PWID communities, we obtained a sample of N = 410 PWID from Southeast Michigan (n = 285 form urban Detroit, and 125 for suburban/rural areas outside Detroit). Participants completed questionnaires detailing socio-demographics, health history, substance use and treatment access, including naloxone. We used multiple logistic regression to examine the predictors of self-reported naloxone access based on participant characteristics (e.g., demographics, health status) and geography (urban vs. suburban/rural). RESULTS: Self-reported naloxone access differed significantly by location (urban = 18.3 %; suburban/rural = 41.9 %). In multivariable analyses, naloxone access was significantly associated with race, household income, employment, health insurance, recent homelessness, prescription opioid usage, Hepatitis A and C status, Hepatitis A vaccination, Hepatitis C testing, access to drug treatment and services, and hospital as the usual place of care. CONCLUSION: Despite recent policies to expand access, our results indicate that naloxone access among high-risk PWID is low. This warrants future research to identify effective channels to reduce barriers and increase naloxone access.

Cost-effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection and a Combined Intervention of Syringe Access and Medication-assisted Therapy for Opioid Use Disorders in an Injection Drug Use Population.

BACKGROUND: There are too many plausible permutations and scale-up scenarios of combination hepatitis C virus (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used a computer simulation to project the health and economic impacts of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct antiviral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+). METHODS: We performed an allocative efficiency study, using a mathematical model to simulate the progression of HCV in PWID and its related consequences. We combined 2 previously validated simulations to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health-sector and societal perspective, with a 15-year time horizon and a discount rate of 3%. RESULTS: From a health-sector perspective (excluding criminal justice system-related costs), 4 potential strategies fell on the cost-efficiency frontier. At 20% coverage, DAAs had an incremental cost-effectiveness ratio (ICER) of $27 251/quality-adjusted life-year (QALY). Combinations of DAA at 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165 985/QALY, $325 860/QALY, and $399 189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA at 20% with MAT+ at 80% was the most effective intervention and was cost saving. While DAA at 20% with MAT+ at 80% was more expensive (eg, less cost saving) than MAT+ at 80% alone without DAA, it offered a favorable value compared to MAT+ at 80% alone ($23 932/QALY). CONCLUSIONS: When considering health-sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together became the most cost-effective intervention.

Untreated alcohol use disorder in people who inject drugs (PWID) in France: a major barrier to HCV treatment uptake (the ANRS-FANTASIO study).

BACKGROUND AND AIMS: Although people who inject drugs (PWID) are the core at-risk population in the hepatitis C virus (HCV) epidemic in industrialized countries, few initiate treatment. Alcohol use disorder (AUD), common within this population, has been identified as a barrier to HCV treatment uptake in the general population. We investigated whether the arrival of new and well-tolerated HCV treatments (direct-acting antivirals: DAA) has improved HCV treatment uptake in French PWID compared with former treatments (pegylated interferon-based treatments: Peg-IFN). DESIGN: Using discrete-time Cox proportional hazards models based on exhaustive care delivery data, we tested for associations between AUD (defined by AUD-related long-term illness status, diagnosis coding during hospitalization and/or AUD pharmacological treatment) and first HCV treatment delivery, after adjusting for gender, age, complementary universal health cover, liver disease severity and type of opioid agonist therapy (OAT) received. Separate analyses were performed for 2012-13 (Peg-IFN era) and 2014-16 (DAA era). SETTING: France. PARTICIPANTS: All French people chronically HCV-infected who received OAT at least once during 2012-16 and were covered by the national health insurance (n = 24 831). MEASUREMENTS: Incidence rate of HCV treatment uptake, hazard ratios associated with AUD and other covariates. FINDINGS: Incidence rate (IR) of HCV treatment uptake per 100 person-years was 6.56, confidence interval (CI) = 6.30-6.84; and IR = 5.70, 95% CI = 5.51-5.89 for Peg-IFN-based treatment (2012-13) and DAA (2014-16), respectively. After multiple adjustment, people with AUD not receiving related medication had 30 and 14% lower Peg-IFN-based treatment and DAA uptake, respectively, than those without AUD [hazard ratio (HR) = 0.70, 95% CI = 0.62-0.80 and HR = 0.86, 95% CI = 0.78-0.94]. No difference was observed between those treated for AUD and those without AUD. CONCLUSIONS: Despite the benefits of direct-acting antiviral treatment, untreated alcohol use disorder appears to remain a major barrier to hepatitis C virus treatment access for people who inject drugs in France.