Optimal control of hepatitis C antiviral treatment programme delivery for prevention amongst a population of injecting drug users.

In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred until the final years of the decade, and is the least cost-effective of the scenarios

Cost-effectiveness of HCV case-finding for people who inject drugs via dried blood spot testing in specialist addiction services and prisons

ObjectivesPeople who inject drugs (PWID) are at high risk for acquiring hepatitis C virus (HCV), but many are unaware of their infection. HCV dried blood spot (DBS) testing increases case-finding in addiction services and prisons. We determine the cost-effectiveness of increasing HCV case-finding among PWID by offering DBS testing in specialist addiction services or prisons as compared to using venepuncture.DesignCost-utility analysis using a dynamic HCV transmission model among PWID, including: disease progression, diagnosis, treatment, injecting status, incarceration and addition services contact.Setting uk interventionDBS testing in specialist addiction services or prisons. Intervention impact was determined by a meta-analysis of primary data.Primary and secondary outcome measuresCosts (in UK £, £1=US$1.60) and utilities (quality-adjusted life years, QALYs) were attached to each state and the incremental cost effectiveness ratio (ICER) determined. Multivariate uncertainty and one-way sensitivity analyses were performed.ResultsFor a £20 000 per QALY gained willingness-to-pay threshold, DBS testing in addiction services is cost-effective (ICER of £14 600 per QALY gained). Under the base-case assumption of no continuity of treatment/care when exiting/entering prison, DBS testing in prisons is not cost-effective (ICER of £59 400 per QALY gained). Results are robust to changes in HCV prevalence; increasing PWID treatment rates to those for ex-PWID considerably reduces ICER (£4500 and £30 000 per QALY gained for addiction services and prison, respectively). If continuity of care is >40%, the prison DBS ICER falls below £20 000 per QALY gained.ConclusionsDespite low PWID treatment rates, increasing case-finding can be cost-effective in specialist addiction services, and in prisons if continuity of treatment/care is ensured

Cost-effectiveness of Universal Hepatitis C Virus Screening of Pregnant Women in the United States

BACKGROUND:Hepatitis C virus' (HCV) chronic prevalence among pregnant women in the United States doubled nationally from 2009-2014 (~0.7%), yet many cases remain undiagnosed. Screening pregnant women is not recommended by the Society of Maternal-Fetal Medicine or the Centers for Disease Control and Prevention, despite new American Association For the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA) guidelines recommending screening for this group. We assessed the cost-effectiveness of HCV screening for pregnant women in the United States. METHODS:An HCV natural history Markov model was used to evaluate the cost-effectiveness of universal HCV screening of pregnant women, followed by treatment after pregnancy, compared to background risk-based screening from a health-care payer perspective. We assumed a HCV chronic prevalence of 0.73% among pregnant women, based on national data. We assumed no Medicaid reimbursement restrictions by fibrosis stage at baseline, but explored differing restrictions in sensitivity analyses. We assessed costs (in US dollars) and health outcomes (in quality-adjusted life-years [QALYs]) over a lifetime horizon, using new HCV drug costs of $25 000/treatment. We assessed mean incremental cost-effectiveness ratios (ICERs) under a willingness-to-pay threshold of$50 000/QALY gained. We additionally evaluated the potential population impact. RESULTS:Universal antenatal screening was cost-effective in all treatment eligibility scenarios (mean ICER <$3000/QALY gained). Screening remained cost-effective at a prevalence of 0.07%, which is the lowest estimated prevalence in the United States (in Hawaii). Screening the ~5.04 million pregnant women in 2018 could result in the detection and treatment of 33 000 women, based on current fibrosis restrictions. CONCLUSIONS:Universal screening for HCV among pregnant women in the United States is cost-effective and should be recommended nationally

Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy

BackgroundInterventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID.MethodsAn HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed.ResultsLarge reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage.ConclusionsCombining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions

Is increased hepatitis C virus case-finding combined with current or 8-week to 12-week direct-acting antiviral therapy cost-effective in UK prisons? A prevention benefit analysis

UNLABELLED: Prisoners have a high prevalence of hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity of care. We assessed the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons compared to status quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies (8-24 weeks) or interferon (IFN)-free direct-acting antivirals (DAAs; 8-12 weeks, 95% sustained virological response, £3300/week). Costs (British pounds, £) and health utilities (quality-adjusted life years) were used to calculate mean incremental cost-effectiveness ratios (ICERs). We assumed 56% referral and 2.5%/25% of referred people who inject drugs (PWID)/ex-PWID treated within 2 months of diagnosis in prison. PWID and ex-PWID or non-PWID are in prison an average 4 and 8 months, respectively. Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/quality-adjusted life years gained compared to current testing/treatment and is 45% likely to be cost-effective under a £20,000 willingness-to-pay threshold. Switching to 8-week to 12-week IFN-free DAAs in prisons could increase cost-effectiveness (ICER £15,090/quality-adjusted life years gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base case), either treatment could be highly cost-effective (ICER<£13,000). HCV case-finding and IFN-free DAAs could be highly cost-effective if DAA cost is 10% lower or with 8 weeks' duration. CONCLUSIONS: Increased HCV testing in UK prisons (such as through opt-out testing) is borderline cost-effective compared to status quo voluntary risk-based testing under a £20,000 willingness to pay with current treatments but likely to be cost-effective if short-course IFN-free DAAs are used and could be highly cost-effective if PWID treatment rates were increased. (Hepatology 2016;63:1796-1808)

The role of a hepatitis C virus vaccine:modelling the benefits alongside direct-acting antiviral treatments

BACKGROUND: Hepatitis C virus (HCV) elimination is being seriously considered globally. Current elimination models require a combination of highly effective HCV treatment and harm reduction, but high treatment costs make such strategies prohibitively expensive. Vaccines should play a key role in elimination but their best use alongside treatments is unclear. For three vaccines with different efficacies we used a mathematical model to estimate the additional reduction in HCV prevalence when vaccinating after treatment; and to identify in which settings vaccines could most effectively reduce the number of treatments required to achieve fixed reductions in HCV prevalence among people who inject drugs (PWID). METHODS: A deterministic model of HCV transmission among PWID was calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID, stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90% efficacies, different rates of treatment and vaccination were introduced. We compared prevalence reductions achieved by vaccinating after treatment to prevent reinfection and vaccinating independently of treatment history in the community; and by allocating treatments and vaccinations to specific risk groups and proportionally across risk groups. RESULTS: Vaccinating after treatment was minimally different to vaccinating independently of treatment history, and allocating treatments and vaccinations to specific risk groups was minimally different to allocating them proportionally across risk groups. Vaccines with 30 or 60% efficacy provided greater additional prevalence reduction per vaccination in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious vaccine in settings with 25 or 50% chronic HCV prevalence among PWID. CONCLUSIONS: Vaccinating after treatment is an effective and practical method of administration. In settings with high chronic HCV prevalence among PWID, even modest coverage with a low-efficacy vaccine could provide significant additional prevalence reduction beyond treatment alone, and would likely reduce the cost of achieving prevalence reduction targets

Behavioural, not biological, factors drive the HCV epidemic among HIV-positive MSM: HCV and HIV modelling analysis including HCV treatment-as-prevention impact.

Background: Uncertainty surrounds why hepatitis C virus (HCV) is concentrated among HIV-positive men who have sex with men (MSM). We used mathematical modelling to explore reasons for these infection patterns, and implications for HCV treatment-as-prevention. Methods: Using a joint MSM HIV/HCV transmission model parameterized with UK behavioural data, we considered how biological (heightened HCV infectivity and reduced spontaneous clearance among HIV-positive MSM) and/or behavioural factors (preferential sexual mixing by HIV status and risk heterogeneity) could concentrate HCV infection in HIV-positive MSM as commonly observed (5-20 times the HCV prevalence in HIV-negative MSM; defined as the HCV ratio). We explored how HCV treatment-as-prevention impact varies under differing HCV ratios. Results: Biological factors produced low HCV ratios ( 10) that were highly sensitive to both factors. Irrespective of the HCV ratio or behavioural/biological factors, HCV treatment of HIV-diagnosed MSM markedly reduced the HCV prevalence among HIV-positive MSM, but less impact was achieved among all MSM for lower HCV ratios. Conclusions: Sexual behaviour patterns likely drive observed HCV infection patterns among HIV-positive MSM. Changes in these patterns could disseminate HCV amongst HIV-negative MSM, limiting the impact of targeting HCV treatment to HIV-diagnosed MSM

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high