Hepatitis C prevention among people who inject drugs: reducing transmission in PWID by scaling up HCV treatment, OST and needle exchange services

Matt Hickman, Natasha Martin, Peter Vickerman

Acknowledgements• NIHR Health Protection Research Unit in Evaluation of Interventions

• Health Protection Scotland: HCV Action Plan

• NIHR PDG Can HCV treatment be delivered to injecting drug users…

• European Commission Drug Prevention and Information Programme (DIPP) “Treatment as Prevention in Europe…”

• NIHR (HS&DR) (12/3070/13) - Assessing the impact and cost-effectiveness of NSP on HCV

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Collaborators:- Sharon J Hutchinson, Graham R Foster, John F Dillon, Fiona Gordon, Javier Vilar, Matthew Cramp, Stephen Ryder, David J Goldberg, Daniela De Angelis, Will Irving, Viv Hope, Noel Craine, Marion Lyons, Norah Palmateer, Esther Aspinall

EPIDEMIOLOGY

> 90% HCV acquired in UK among PWID

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)

OST/HIGH COVERAGE NSP (HC_NSP) EFFECTIVENESS

• Use recent pooled UK evidence for impact of harm reduction on an individual’s risk of recent HCV infection1

Effect Estimates AOR1 95% CIHC_NSP 0.48 0.3 0.9OST 0.41 0.2 0.8OST and HC_NSP 0.21 0.1 0.51 adjusted for: gender, crack, homeless, injecting duration

HC_NSP is defined as exchanging more syringes than you inject

Turner K et al. Addiction 2011; 106:1978-88

CAN SCALING UP COVERAGE OF OST & NSP ACHIEVE FURTHER SUBSTANTIAL REDUCTIONS IN HCV AMONG PWID

Modeling transitions between OST and NSP & transmission of HCV

Not 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 Addiction 2012 doi:10.1111/j.1360-0443.2012.03932.x

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%-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)

Vickerman et al Addiction 2012 doi:10.1111/j.1360-0443.2012.03932.x

SCALING UP HCV TREATMENT AS PREVENTION

Non-SVR infected

PWID

Chronically infected PWID

UninfectedPWID

Antiviral treatment

Allow for re-infection

NewPWID

Cease/die Acutely infected PWID Infection

Spontaneous clearance

Need Dynamic Model to Assess Intervention Impact on HCV Prevalence

Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, and Hickman M. J Hep 2011; 54:1137-44

Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, and Hickman M. J Hep 2011; 54:1137-44

MODELLING HCV TREATMENT AS PREVENTIONHCV RELATIVE PREVALENCE REDUCTIONS AT 10 YEARS WITH PEGIFN+RBV

Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programmes, and opiate substitution therapy. Clinical Infectious Diseases 2013

40% chronic prevalence

• Dark red: modest (<20%) impact, high HCV

• Orange: ~50% impact

• White: >80% impact

COMBINATION PREVENTION SCALE-UP (OST/NSP/DAAS):10 YEAR RELATIVE PREVALENCE REDUCTIONS WITH NO BASELINE COVERAGE OF OST/NSP AND USING DAAs

• >40% reduction requires HCV treatment

• OST&NSP increases benefit of HCV treatment

HCV TREATMENT & TREATING PWID IS COST-EFFECTIVE

SO IN NEW DAA ERA - WHICH PATIENTS SHOULD BE TARGETED?

Cost-effectiveness efficiency frontiers – 20% chronic HCV new DAA

50 100 150 200 250 300 350 400 450£0

£500,000

£1,000,000

£1,500,000

£2,000,000

£2,500,000

£3,000,000

£3,500,000

£4,000,000

£4,500,000

£5,000,000

PWID, moderate

Ex/non PWID, moderate

PWID, mild

Ex/non PWID mild

Mean incremental QALYs

Mea

n in

crem

enta

l co

sts

(£)

Treating PWID/non-exPWID with mild or moderate HCV compared to delayed treatment until cirrhosis. Treatment scenarios above frontier are dominated (more expensive, fewer benefits)

0 50 100 150 200 250 300 350 400 450 500£0

£500,000£1,000,000£1,500,000£2,000,000£2,500,000£3,000,000£3,500,000£4,000,000£4,500,000£5,000,000

PWID, moderate

Ex/non PWID, moderate

PWID, mild

Ex/non PWID mild

Mean incremental QALYs

Me

an

in

cre

me

nta

l c

os

ts (

£)

Cost-effectiveness efficiency frontiers – 40% chronic HCV new DAA

0 50 100 150 200 250 300 350 400 450 500£0

£500,000

£1,000,000

£1,500,000

£2,000,000

£2,500,000

£3,000,000

£3,500,000

£4,000,000

£4,500,000

£5,000,000

PWID, moderate

Ex/non PWID, moderate

PWID, mild

Ex/non PWID mild

Mean incremental QALYs

Me

an

in

cre

me

nta

l c

os

ts

£)

Cost-effectiveness efficiency frontiers – 60% chronic HCV new DAA

ARE CURRENT HCV TREATMENT RATES SUFFICIENT?

Blue: Baseline in 2014White box: 2024, No scale-up, ITT SVR with IFN/RBV

Bristol E London Manchester Nottingham Plymouth Dundee N WalesHCV

chro

nic

prev

alen

ce a

mon

g PW

ID (%

)TREATMENT IMPACT IN SEVEN UK CITIES WITH CURRENT RATES/SVR

Martin NK, JVH 2014

Blue: Baseline in 2014White box: 2024, No scale-up, ITT SVR with IFN/RBVBlack: 2024, Scale-up to 26/1000 annually with IFN-free DAAs (all genotypes) in 2016

Bristol E London Manchester Nottingham Plymouth Dundee N WalesHCV

chro

nic

prev

alen

ce a

mon

g PW

ID (%

)TREATMENT IMPACT IN SEVEN UK CITIES WITH SCALE-UP/DAAs

Martin NK, JVH 2014

HCV ELIMINATION – MYTH OR REALITY

Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programmes, and opiate substitution therapy. Clinical Infectious Diseases 2013

COMBINATION PREVENTION SCALE-UP (from 50% OST/NSP & DAAS):10 YEAR RELATIVE PREVALENCE REDUCTIONS 40% CHRONIC HCV

Towards Elimination: scaling up HCV treatment rates to 30-40 per 1000PWID & 60% OST&NSP coverage reduces HCV prevalence by 60-80% in 10 years.

HCV prevalence reduction – combining interventions

• HCV treatment scale-up essential to achieve substantial reductions in HCV prevalence

• Current treatment rates maybe insufficient to achieve observable reductions (in UK)

• OST&NSP increase benefits of HCV treatment as prevention

• HCV treatment of PWID is cost-effective – and in many scenarios more cost-effective than treating ex/non-PWID or delaying treatment until cirrhosis.

• Now need empirical evidence to test model projections