department of social medicine university of bristol the primary prevention of hepatitis c among...

Department ofSOCIAL MEDICINE

University ofBRISTOL

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

Modelling Impact of Prevention & HCV treatment

Case Finding - Implications



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 carriers2007: Estimated annual new

chronic HBV infections in England and Wales

UK

HB

V

infe

ctio

ns

Estimates of chronic HBV infections

Department of Healthestimate

Hepatitis B Foundation

estimate

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

Chronic HBV infectionimported by people whoacquired infection prior

to migration6,571 per year 0

50000

100000

150000

200000

250000

300000

350000

Hahné S et 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

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

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



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


Site Year Design N HCV+ve Incidence Sero-conversions

Bristol 2006 RDS 299 59% 40 per 100py 14

Leeds 2008 RDS 302 60% 7.6 per 100py 2

Birmingham 2009 RDS 310 42% 5.2 per 100py 2

Glasgow 2008-09 C'sectional NSP 947 70% 10.0 per

100py 6

Wales 2004-06 Follow-up 406/700 26% 5.6 per 100 py 17

London 2001-02 Follow-up 282/428 43% 42 per 100py 49



Overall (I-squared = 46.5%, p = 0.096)

Study

Leeds

ID

London

Wales

Birmingham

Bristol

Glasgow

0.48 (0.28, 0.84)

1.31 (0.08, 20.91)

ES (95% CI)

0.50 (0.20, 1.27)

0.17 (0.05, 0.61)

1.54 (0.14, 16.97)

1.05 (0.37, 3.00)

0.07 (0.01, 0.57)

100.00

%

4.02

Weight

35.98

19.84

5.35

28.11

6.69

0.48 (0.28, 0.84)

1.31 (0.08, 20.91)

ES (95% CI)

0.50 (0.20, 1.27)

0.17 (0.05, 0.61)

1.54 (0.14, 16.97)

1.05 (0.37, 3.00)

0.07 (0.01, 0.57)

100.00

%

4.02

Weight

35.98

19.84

5.35

28.11

6.69

1.00779 1 128

Effect of opiate substitution treatment on HCV incidence



Intervention EffectIntervention coverage New HCV

infectionUnadjust

ed OR 95% CI Adjusted OR 95% CI

(a) OST On OST* 2.6% 0.36 0.19 – 0.70 0.41 0.21 – 0.82Not on OST 6.9%(b) NSP ** ≥ 100% coverage 3.8% 0.52 0.28 -0.99 0.48 0.25 – 0.93<100% coverage 7.0% (c) COMBINEDFull HR: OST and no injecting or ≥100% NSP 2.0% 0.19 0.08 – 0.47 0.21 0.08 – 0.52

≥100% NSP, No OST 5.3% 0.52 0.23 – 1.15 0.5 0.22 – 1.12<100% NSP, On OST 4.3% 0.41 0.15 – 1.12 0.48 0.17 – 1.33Minimal HR 9.8%

Adjusted for the following covariates: female gender (AOR 2.1); homeless in last year (2,9); injected crack in last month (1.9); duration injecting <2.5 years (1.0)

* Includes or ** Excludes 86 cases (involving 0 new HCV infections) who were on OST but reported no injections in the last month (cross-sectional studies) or last year (cohort studies).




But what about the effect on HCV prevalence?

20 million syringes distributed annually

5 fold increase in methadone prescription in last 10 years

BUT: little impact on HCV prevalence

England and Wales data

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



CAN SCALING UP THE COVERAGE OF EXISTING INTERVENTIONS REDUCE HCV PREVALENCE?



Modeling transitions between OST and NSP &

transmission of HCVNot on OST

or NSP xo

On OST only xm

On NSP only xn

On OSTand NSP xnm

Leaving NSP δ

Recruited on to OST α

Leaving NSP δ

Leaving OST γ

Leaving OST γ

Recruited on to OST α

Recruited on to NSP β

Recruited on to NSP β

Vickerman et al under review

Susceptible to HCV X

Chronic infected with

HCV Y

Rate of infection leading to chronic infection λ(1-ρ)

Rate of cessation μ

Rate of cessation μ

Rate of entry μ(X+Y)

Rate of infection leading to spontaneous clearance λρ



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

60%, 70%, 80%

0%

10%

20%

30%

40%

50%

60%

70%

80%

Without 60% 70% 80% 60% 70% 80% 60% 70% 80%

NSP/OST 5 years 10 years 20 years

HC

V p

revale

nce

(baseli

ne w

as 4

0%

pre

vale

nce)

Effect of scaling up both OST and NSP to 60%, 70% and 80% coverage for different durations (baseline was 50% coverage)



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?



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



Non-responder infected IDUs

HCV-infected active IDUs

Uninfectedactive IDUs

Antiviral treatment

Allow for reinfection

InfectionOutcome: Impact on

HCV prevalence

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

New Injectors

Cease/die

DYNAMIC HCV TRANSMISSION MODELDYNAMIC HCV TRANSMISSION MODEL



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

PREVENTION IMPACT RESULTS: PREVENTION IMPACT RESULTS: PREVALENCE REDUCTIONS AT 10 YEARSPREVALENCE REDUCTIONS AT 10 YEARS



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 (4034%) 30% reduction in 10 years (4028%) Halved in 20 years (40 20%)

Martin et al. J Hepatology 2011



BUT IS TREATING IDU FOR HCV COST EFFECTIVE?



MODEL FORMULATIONMODEL 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 RESULTSCOST-EFFECTIVENESS RESULTS

Mean incremental cost-effectiveness ratio, ICER (cost per QALY gained)

IDU Ex/non IDU

20% prevalence £521 Dominated

40% prevalence £2,359 Dominated

60% prevalence Dominated £6,803

Martin et al Hepatology 2012



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



INTERVENTIONS TO PROMOTE INTERVENTIONS TO PROMOTE HCV TESTING AMONG IDUHCV 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):250-2542 Cullen et al. 2011 J Pub Health (Ox) Epub



INTERVENTIONS TO PROMOTE INTERVENTIONS TO PROMOTE HCV/HBV TESTING AMONG UK MIGRANTSHCV/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.



IMPLICATIONS



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 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

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

department of social medicine university of bristol the primary prevention of hepatitis c among...

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