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

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 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

A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data.

Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts

Can the UNAIDS modes of transmission model be improved? A comparison of the original and revised model projections using data from a setting in west Africa.

OBJECTIVE: The UNAIDS modes of transmission model (MoT) is a user-friendly model, developed to predict the distribution of new HIV infections among different subgroups. The model has been used in 29 countries to guide interventions. However, there is the risk that the simplifications inherent in the MoT produce misleading findings. Using input data from Nigeria, we compare projections from the MoT with those from a revised model that incorporates additional heterogeneity. METHODS: We revised the MoT to explicitly incorporate brothel and street-based sex-work, transactional sex, and HIV-discordant couples. Both models were parameterized using behavioural and epidemiological data from Cross River State, Nigeria. Model projections were compared, and the robustness of the revised model projections to different model assumptions, was investigated. RESULTS: The original MoT predicts 21% of new infections occur in most-at-risk-populations (MARPs), compared with 45% (40-75%, 95% Crl) once additional heterogeneity and updated parameterization is incorporated. Discordant couples, a subgroup previously not explicitly modelled, are predicted to contribute a third of new HIV infections. In addition, the new findings suggest that women engaging in transactional sex may be an important but previously less recognized risk group, with 16% of infections occurring in this subgroup. CONCLUSION: The MoT is an accessible model that can inform intervention priorities. However, the current model may be potentially misleading, with our comparisons in Nigeria suggesting that the model lacks resolution, making it challenging for the user to correctly interpret the nature of the epidemic. Our findings highlight the need for a formal review of the MoT

Investment case for eliminating mother-to-child transmission of syphilis: promoting better maternal and child health and stronger health systems

Mother-to-child transmission (MTCT) of syphilis (commonly referred to as “congenital syphilis”) is relatively simple to eliminate and it is inexpensive to detect and treat, making it a possible “easy win” in terms of cost, feasibility and speed of scale-up. Investing in screening and treatment for syphilis in pregnant women ranks as one of the most cost-effective antenatal interventions. Screening all pregnant women, using simple and low-cost technologies, is feasible, even in low-resource settings. Syphilis is easily cured with penicillin, and MTCT of syphilis is easily prevented when pregnant mothers with syphilis infection are identified early and treated promptly. Penicillin is off patent, widely available, on the World Health Organization (WHO) list of essential medicines and, above all, inexpensive

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