[Show abstract][Hide abstract]ABSTRACT: New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.
No preview · Article · Mar 2016 · Journal of Viral Hepatitis
[Show abstract][Hide abstract]ABSTRACT: Background:
We report on the hepatitis C virus(HCV) epidemic among HIV-positive men who have sex with men(MSM) in the UK and model its trajectory with or without scaled-up HCV direct-acting antivirals(DAAs).
A dynamic HCV transmission model among HIV-diagnosed MSM in the UK was calibrated to HCV prevalence(Ab+ or RNA+), incidence, and treatment from 2004-2011 among HIV-diagnosed MSM in the UK collaborative HIV cohort(UK CHIC). The epidemic was projected with: current or scaled-up HCV treatment, with or without a 20% behavioral risk reduction.
HCV prevalence among HIV-positive MSM in UK CHIC increased from 7.3% in 2004 to 9.9% in 2011, whereas primary incidence was flat(1.02-1.38 per 100 person-years). Over the next decade, modelling suggests 94% of infections are attributable to high-risk individuals, comprising 7% of the population. Without treatment, HCV chronic prevalence could have been 38% higher in 2015(11.9% vs 8.6%). With current treatment and SVR rates(status quo), chronic prevalence is likely to increase to 11% by 2025, but stabilize with DAA introduction in 2015. With DAAs scale-up to 80% within one year of diagnosis (regardless of disease stage), 20%/yr thereafter, chronic prevalence could reduce by 71% (to 3.2%) compared to status quo in 2025. With additional behavioural interventions, chronic prevalence could reduce further to <2.5% by 2025.
Epidemiological data and modelling suggest a continuing HCV epidemic among HIV-diagnosed MSM in the UK driven by high-risk individuals, despite high treatment rates. Substantial reductions in HCV transmission could be achieved through scale-up of DAAs and moderately effective behavioural interventions.
Preview · Article · Feb 2016 · Clinical Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: Background:
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 assess 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 IFN-free DAAs(8-12 weeks, 95% SVR, £3300/wk). Costs(GBP£) and health utilities(quality-adjusted life-years,QALYs) were used to calculate mean incremental cost-effectiveness ratios(ICERs). We assume 56% referral and 2.5%/25% of referred people who inject drugs(PWID)/exPWID treated within 2 months of diagnosis in prison. PWID and ex/nonPWID are in prison an average 4/8 months, respectively.
Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/QALY gained compared to current testing/treatment, and is 45% likely to be cost-effective under a £20,000 willingness-to-pay(WTP) threshold. Switching to 8-12 week IFN-free DAAs in prisons could increase cost-effectiveness(ICER £15,090/QALY 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 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 WTP 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. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract]ABSTRACT: Background:
We determine the optimal HCV treatment prioritization strategy for interferon-free HCV direct-acting antivirals(IFN-free DAAs) by disease stage and risk status incorporating treatment of people who inject drugs(PWID).
A dynamic HCV transmission and progression model compares the cost-effectiveness of treating patients early versus delaying until cirrhosis for patients with mild or moderate fibrosis where PWID chronic HCV prevalence is 20, 40 or 60%. Treatment is 12 weeks, £3300/wk, 95% sustained viral response, varied by genotype/stage in alternative scenarios. We estimate long-term health costs(in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years gained(QALYs) using a £20,000 willingness-to-pay per QALY threshold. We rank strategies with Net Monetary Benefit(NMB); negative NMB implies delay treatment.
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 is 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 are averted. One extra HCV-related death is averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied SVR/duration by genotype/fibrosis stage.
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.
No preview · Article · Feb 2016 · Journal of Hepatology
[Show abstract][Hide abstract]ABSTRACT: Model-based economic evaluations of new interventions have shown that user behaviour (uptake) is a critical driver of overall impact achieved. However, early economic evaluations, prior to introduction, often rely on assumed levels of uptake based on expert opinion or uptake of similar interventions. In addition to the likely uncertainty surrounding these uptake assumptions, they also do not allow for uptake to be a function of product, intervention, or user characteristics. This letter proposes using uptake projections from discrete choice experiments (DCE) to better parameterize uptake and substitution in cost-effectiveness models. A simple impact model is developed and illustrated using an example from the HIV prevention field in South Africa. Comparison between the conventional approach and the DCE-based approach shows that, in our example, DCE-based impact predictions varied by up to 50% from conventional estimates and provided far more nuanced projections. In the absence of observed uptake data and to model the effect of variations in intervention characteristics, DCE-based uptake predictions are likely to greatly improve models parameterizing uptake solely based on expert opinion. This is particularly important for global and national level decision making around introducing new and probably more expensive interventions, particularly where resources are most constrained.
No preview · Article · Jan 2016 · Health Economics
[Show abstract][Hide abstract]ABSTRACT: 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).
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.
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.
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.
[Show abstract][Hide abstract]ABSTRACT: Purpose of review:
The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk - such as people who inject drugs (PWID) - irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID.
There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential 'prevention benefit' of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and 'prevention benefit' hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures.
Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.
No preview · Article · Nov 2015 · Current Opinion in Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: In many settings, interventions targeting female sex workers (FSWs) could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP) could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use—one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed ‘pimps’) was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used.
[Show abstract][Hide abstract]ABSTRACT: Background:
Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated.
We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital.
We estimated that 3709 million people (range: 3440-3878 million) aged 0-49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67-212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific.
The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection.
[Show abstract][Hide abstract]ABSTRACT: Objectives:
The objective of this study is to understand the association between HIV and hepatitis C virus (HCV) among people who inject drugs (PWIDs) in the Middle East and North Africa (MENA), and to estimate HIV epidemic potential among PWIDs using HCV prevalence.
Using data from a systematic review of HIV and HCV among PWID in MENA, we conducted two analyses, stratified by HIV epidemic state: a meta-analysis of the risk ratio of HCV to HIV prevalence (RRHCV/HIV) using DerSimonian-Laird random-effects models, and multivariable linear regression predicting log HIV prevalence. The HCV-HIV association from both analyses was used to estimate HIV prevalence at endemic equilibrium. We compared predicted with current HIV prevalence to classify HIV epidemic potential at country-level as low, medium or high, using predefined criteria.
The review identified 88 HCV prevalence measures among PWID in MENA, of which 54 had a paired HIV prevalence measure. The pooled RRHCV/HIV were 16, 4 and 3 in low-level, emerging and established HIV epidemics, respectively. There was a significant linear relationship between HCV and HIV at endemic equilibrium (P = 0.002). The predicted endemic HIV prevalence ranged between 8% (Tunisia) and 22% (Pakistan). Of the nine countries with data, five have high and three medium HIV epidemic potential. Only one country, Pakistan, appears to have reached saturation.
HCV prevalence could be a predictor of future endemic HIV prevalence. In MENA, we predict that there will be further HIV epidemic growth among PWID. The proposed methodology can identify PWID populations that should be prioritized for HIV prevention interventions.
Full-text · Article · Sep 2015 · AIDS (London, England)
[Show abstract][Hide abstract]ABSTRACT: To estimate the impact and cost-effectiveness of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordant couples in Nigeria.
Mathematical and cost modelling.
A deterministic model of HIV-1 transmission within a cohort of serodiscordant couples and to/from external partners was parameterized using data from Nigeria and other African settings. The impact and cost-effectiveness were estimated for condom promotion, PrEP and/or TasP, compared with a baseline where antiretroviral therapy (ART) was offered according to 2010 national guidelines (CD4 <350 cells/μl) to all HIV-positive partners. The impact was additionally compared with a baseline of current ART coverage (35% of those with CD4 <350 cells/μl). Full costs (in US $2012) of programme introduction and implementation were estimated from a provider perspective.
Substantial benefits came from scaling up ART to all HIV-positive partners according to 2010 national guidelines, with additional smaller benefits of providing TasP, PrEP or condom promotion. Compared with a baseline of offering ART to all HIV-positive partners at the 2010 national guidelines, condom promotion was the most cost-effective strategy [US $1206/disability-adjusted-life-year (DALY)], the next most cost-effective intervention was to additionally give TasP to HIV-positive partners (incremental cost-effectiveness ratio US $1607/DALY), followed by additionally giving PrEP to HIV-negative partners until their HIV-positive partners initiate ART (US $7870/DALY). When impact was measured in terms of infections averted, PrEP with condom promotion prevented double the number of infections as condom promotion alone.
The first priority intervention for serodiscordant couples in Nigeria should be scaled up ART access for HIV-positive partners. Subsequent incremental benefits are greatest with condom promotion and TasP, followed by PrEP.
Full-text · Article · Sep 2015 · AIDS (London, England)
[Show abstract][Hide abstract]ABSTRACT: The burden of hepatitis C virus (HCV) is high among people who inject drugs (PWID) and prisoners, and increasing among HIV-infected MSM, who are key populations for HCV transmission in high-income countries and may also play a role in many in low- and middle-income countries. There is an increasing interest in the use of HCV antiviral treatment for prevention in these populations.
Numerous theoretical modelling studies have explored the potential impact of HCV treatment for prevention among PWID in a range of global settings, generally finding that modest and achievable levels of HCV treatment, especially with interferon-free direct-acting antiviral therapy (IFN-free DAAs), could substantially reduce HCV chronic prevalence among PWID within the next 10-20 years. In addition, modelling studies have shown HCV testing and treatment in prison (including prevention benefits) could be cost-effective if continuity of care is ensured, or HCV treatments are shortened with DAAs. Modelling work among HIV-infected MSM has shown that further HCV treatment scale-up is likely required despite high treatment rates in this population. However, no empirical studies have explored whether HCV treatment can reduce HCV prevalence and prevent onwards transmission among those at risk of transmission.
HCV treatment for key populations such as PWID, prisoners and MSM could become an important HCV prevention intervention, especially in the IFN-free DAA era. However, there is an urgent need to test these hypotheses through empirical studies.
No preview · Article · Sep 2015 · Current opinion in HIV and AIDS
[Show abstract][Hide abstract]ABSTRACT: HIV impacts heavily on the operating costs of companies in sub-Saharan Africa, with many companies now providing antiretroviral therapy (ART) programmes in the workplace. A full cost-benefit analysis of workplace ART provision has not been conducted using primary data. We developed a dynamic health-state transition model to estimate the economic impact of HIV and the cost-benefit of ART provision in a mining company in South Africa between 2003 and 2022.
A dynamic health-state transition model, called the Workplace Impact Model (WIM), was parameterised with workplace data on workforce size, composition, turnover, HIV incidence, and CD4 cell count development. Bottom-up cost analyses from the employer perspective supplied data on inpatient and outpatient resource utilisation and the costs of absenteeism and replacement of sick workers. The model was fitted to workforce HIV prevalence and separation data while incorporating parameter uncertainty; univariate sensitivity analyses were used to assess the robustness of the model findings. As ART coverage increases from 10% to 97% of eligible employees, increases in survival and retention of HIV-positive employees and associated reductions in absenteeism and benefit payments lead to cost savings compared to a scenario of no treatment provision, with the annual cost of HIV to the company decreasing by 5% (90% credibility interval [CrI] 2%-8%) and the mean cost per HIV-positive employee decreasing by 14% (90% CrI 7%-19%) by 2022. This translates into an average saving of US$950,215 (90% CrI US$220,879-US$1.6 million) per year; 80% of these cost savings are due to reductions in benefit payments and inpatient care costs. Although findings are sensitive to assumptions regarding incidence and absenteeism, ART is cost-saving under considerable parameter uncertainty and in all tested scenarios, including when prevalence is reduced to 1%-except when no benefits were paid out to employees leaving the workforce and when absenteeism rates were half of what data suggested. Scaling up ART further through a universal test and treat strategy doubles savings; incorporating ART for family members reduces savings but is still marginally cost-saving compared to no treatment. Our analysis was limited to the direct cost of HIV to companies and did not examine the impact of HIV prevention policies on the miners or their families, and a few model inputs were based on limited data, though in sensitivity analysis our results were found to be robust to changes to these inputs along plausible ranges.
Workplace ART provision can be cost-saving for companies in high HIV prevalence settings due to reductions in healthcare costs, absenteeism, and staff turnover. Company-sponsored HIV counselling and voluntary testing with ensuing treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with high HIV prevalence.
[Show abstract][Hide abstract]ABSTRACT: Evaluation of HIV large scale interventions programme is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use (CU) 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 a dynamic HIV transmission dynamics model to estimate CU 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 CU is critical in the context studied, due to the very limited amount of CU and HIV data available We consider various novel formulations to explore the trajectory of CU in time, based on diffusion-driven trajectories and smooth sigmoid curves. Extensive series of numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in CU 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 illustrates how it can help evaluate HIV intervention from few observational studies and suggests that these methods
can potentially be applied in many different contexts.
No preview · Article · Aug 2015 · Journal of the Royal Statistical Society Series C Applied Statistics