Matt hickman natasha martin peter vickerman daniela de angelis
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The primary prevention of hepatitis C among injectors: model projections of the impact of opiate substitution therapy, needle exchange and antiviral therapy. Matt Hickman Natasha Martin, Peter Vickerman, Daniela De Angelis. Primary Prevention of HCV. Epidemiology Intervention Effectiveness

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Matt Hickman Natasha Martin, Peter Vickerman, Daniela De Angelis

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Matt hickman natasha martin peter vickerman daniela de angelis

The primary prevention of hepatitis C among injectors: model projections of the impact of opiate substitution therapy, needle exchange and antiviral therapy

Matt Hickman

Natasha Martin, Peter Vickerman, Daniela De Angelis


Primary prevention of hcv

Primary Prevention of HCV

  • Epidemiology

  • Intervention Effectiveness

  • Modelling Impact of Prevention & HCV treatment

  • Case Finding - Implications


Public health importance

Public Health Importance

  • In UK liver disease is 5th commonest cause of death

  • In UK HCV/HBV 2nd most important cause

  • Worldwide HCV infection causes ~1/4 liver disease (over 350,000 deaths per year)


Uk majority of chronic hbv infection results from the migration of hbv carriers

UK: Majority of chronic HBV infection results from the migration of HBV carriers

2007: Estimated annual new chronic HBV infections in England and Wales

Estimates of chronic HBV infections

Chronic HBV infection arising from acute HBV infection in resident population 269 per year

Hepatitis B

Foundation

estimate

350000

UK HBV infections

Department

of Health

estimate

300000

250000

200000

150000

Chronic HBV infection

imported by people who

acquired infection prior

to migration

6,571 per year

100000

50000

0

Hahné Set al. J Clin Virol 2004;29:211–20. Hepatitis B Foundation UK. Rising Curve: Chronic Hepatitis B Infection in the UK (2007)


Estimated number of people infected with hcv e w

Estimated number of people infected with HCV: E&W

~15,000 White; 11,000 (IPB)

Sweeting et al. Biostatistics 2008; De Angelis et al, Statistics in Med Research 2009; Ross et al EJPH 2011


Matt hickman natasha martin peter vickerman daniela de angelis

Intervention effectiveness: Emerging evidence that ost and NSP reducing hcv incidence during exposure

Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x


Pooling uk evidence on intervention impact

Pooling UK evidence on intervention impact

Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x


Intervention effect

Intervention Effect

Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x


But what about the effect on hcv prevalence

But what about the effect on HCV prevalence?

England and Wales data

  • 20 million syringes distributed annually

  • 5 fold increase in methadone prescription in last 10 years

  • BUT: little impact on HCV prevalence

Sweeting, M., et al., AJE 2009. 170: 352-60


Can scaling up the coverage of existing interventions reduce hcv prevalence

Can scaling up the coverage of existing interventions reduce HCV prevalence?


Modeling transitions between ost and nsp transmission of hcv

Modeling transitions between OST and NSP & transmission of HCV

Vickerman et al under review


Impact of changing coverage of ost and nsp from 50 0 60 70 80

Impact of changing coverage of OST and NSP from 50%: 0%, 60%, 70%, 80%


Implications

Implications

  • NSP and OST can reduce HCV incidence

  • Introducing OST & NSP will avert infections

  • OST is critical

  • BUT unclear whether alone NSP and OST could be lead to substantial reductions HCV prevalence

    • In UK sites already have high coverage sustained interventions & 40% chronic HCV prevalence in IDU

  • Other prevention options needed

    • Could HCV treatment have an impact?


Could scaling up hcv treatment have an impact on hcv prevention

Could scaling up HCV treatment have an impact on HCV prevention?


Hcv antiviral treatment barriers among active idus

HCV antiviral treatment: Barriers among active IDUs

  • Antiviral treatment effective (~60%) for curing HCV infection and approved for active injecting drug users (IDUs)

  • BUT few currently being treated (<1%)

  • Perceived reluctance/concern over:

    • Non-completion/compliance

    • Re-infection following treatment


Matt hickman natasha martin peter vickerman daniela de angelis

DYNAMIC HCV TRANSMISSION MODEL

Non-responder infected IDUs

Allow for

reinfection

Antiviral

treatment

New Injectors

Uninfected

active IDUs

HCV-infected active IDUs

Cease/die

Outcome:

Impact on

HCV prevalence

Infection

Martin et al. J Hepatology 2011; J Theoretical Biology 2011


Prevention impact results prevalence reductions at 10 years

PREVENTION IMPACT RESULTS: PREVALENCE REDUCTIONS AT 10 YEARS

  • Population of 3500 IDUs, 1400 chronic infections

    • 70 treated annually (20 per 1000 IDUs)

      • 30% reduction by 2022 (40%  28%)

    • 140 treated annually (40 per 1000 IDUs)

      • 58% reduction by 2022 (40%  17%)

Martin et al. J Hepatology 2011


Model projections through time 5 10 20 years annually treating 20 per 1000 idus

Model projections through time (5, 10, 20 years) annually treating 20 per 1000 IDUs

  • Swift and substantial reductions at low prevalence

    • Significant reductions even at high prevalence

  • 3500 IDUs, 1400 infected (40% prevalence), 70 treated/yr

    • 15% reduction in 5 years (4034%)

    • 30% reduction in 10 years (4028%)

    • Halved in 20 years (40 20%)

Martin et al. J Hepatology 2011


But is treating idu for hcv cost effective

But is treating iDU for hcv cost effective?


Model formulation

MODEL FORMULATION

  • Extend ‘infected’ state to include HCV disease progression stages

  • Attach health care costs and quality-adjusted life years (QALYs) to each state


Cost effectiveness results

COST-EFFECTIVENESS RESULTS

Martin et al Hepatology 2012


Incremental cost per qaly gained reduced treatment success rates for idu

INCREMENTAL COST PER QALY GAINED:REDUCED TREATMENT SUCCESS RATES FOR IDU

UK cost-effectiveness threshold

Martin et al Hepatology 2012


Nice economic analysis ways to promote offer testing of hbv hcv in at risk populations

NICE ECONOMIC ANALYSIS: WAYS TO PROMOTE/OFFER TESTING OF HBV/HCV IN AT RISK POPULATIONS


Interventions to promote hcv testing among idu

INTERVENTIONS TO PROMOTE HCV TESTING AMONG IDU

  • Introducing HCV dried blood spot testing in prisons and specialist addiction services

    • Pilot 1 UK cluster randomized controlled trial

    • Increased testing rate by 2.63 and 3.61-fold in addiction services and prisons, respectively.

  • General practitioner (GP) education and remuneration for targeted testing of former-IDU aged 30-54 years old

    • Cullen et al. 20112 non-randomized controlled trial in Scotland

    • Increased testing rate by 3.40-fold, also increased proportion positive HCV tests (yield)

1Hickman et al. 2008 J Viral Hep 15(4):250-254

2 Cullen et al. 2011 J Pub Health (Ox) Epub


Interventions to promote hcv hbv testing among uk migrants

INTERVENTIONS TO PROMOTE HCV/HBV TESTING AMONG UK MIGRANTS

  • Less evidence for effective interventions in this group.

  • Modelled hypothetical GP intervention

    • Based on Lewis et al 20111: Pakistani/British Pakistani people registered at GPs written and invited for an HCV/HBV test

1Lewis H, et al. Gut, 2011. 60 (Suppl 2) a26.


Implications1

Implications


Nice pdg

NICE PDG

  • Consultation on recommendations – June

  • IF more people diagnosed AND undergo treatment then case finding likely to be cost-effective...


Scale up from modelling to reality empirical data needed

Scale-up – from modelling to reality – empirical data needed

  • Trouble with models

    • Theoretical: projections not observations

    • Incorporate/test heterogeneity/ combine interventions… but empirical evidence required

  • NIHR PDG Grant

    • “Can HCV treatment be delivered to injecting drug users in order to reduce HCV transmission and prevalence in the population: an empirical demonstration and evaluation”


Scaling up hcv treatment and prevention

Scaling up HCV treatment and prevention

  • Audit current HCV treatment caseload

    • how far away from number required to observe impact in population

    • Pilot/develop HCV treatment in community

  • NIHR RfPB “Script in a day for injecting drug users: feasibility trial”

    • RCT to evaluate accelerated access to opiate substitution therapy from BDP to establish whether increases uptake and retains patients in treatment


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