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 costeffectiveness 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
~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
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% CI
HC_NSP
0.48
0.3
0.9
OST
0.41
0.2
0.8
OST and HC_NSP
0.21
0.1
0.5
1 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
Rate of entry
μ(X+Y)
Leaving
OST γ
Leaving
NSP δ
Recruited on
to OST α
Recruited on
to NSP β
On OST
only xm
On NSP
only xn
Leaving
NSP δ
Susceptible
to HCV X
Rate of
cessation μ
Rate of infection leading
to chronic infection λ(1-ρ)
Leaving
OST γ
Recruited on
to NSP β
Rate of infection leading to
spontaneous clearance λρ
Recruited on
to OST α
On OST
and NSP xnm
Vickerman et al Addiction 2012
doi:10.1111/j.1360-0443.2012.03932.x
Chronic
infected with
HCV Y
Rate of
cessation μ
HCV prevalence
(baseline was 40% prevalence)
Impact of changing coverage of OST
and NSP from 50%: 0%, 60%-80%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Without
NSP/OST
60%
70%
5 years
80%
60%
70%
80%
10 years
60%
70%
80%
20 years
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
Need Dynamic Model to Assess
Intervention Impact on HCV Prevalence
New
PWID
Allow for
re-infection
Uninfected
PWID
Cease/die
Infection
Antiviral
treatment
Spontaneous
clearance
Non-SVR
infected
PWID
Chronically
infected PWID
Acutely
infected
PWID
Martin NK, Vickerman P, Foster GR, Hutchinson SJ,
Goldberg DJ, and Hickman M. J Hep 2011; 54:1137-44
MODELLING HCV TREATMENT AS PREVENTION
HCV RELATIVE PREVALENCE REDUCTIONS AT 10 YEARS WITH PEGIFN+RBV
Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg
DJ, and Hickman M. J Hep 2011; 54:1137-44
COMBINATION PREVENTION SCALE-UP (OST/NSP/DAAS):
10 YEAR RELATIVE PREVALENCE REDUCTIONS WITH NO BASELINE
COVERAGE OF OST/NSP AND USING DAAs
40% chronic prevalence
• Dark red: modest (<20%)
impact, high HCV
• Orange: ~50% impact
• White: >80% impact
• >40% reduction requires
HCV treatment
• OST&NSP increases
benefit of HCV treatment
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
HCV TREATMENT & TREATING
PWID IS COST-EFFECTIVE
SO IN NEW DAA ERA - WHICH
PATIENTS SHOULD BE
TARGETED?
Mean incremental costs (£)
Cost-effectiveness efficiency frontiers
– 20% chronic HCV new DAA
£5,000,000
£4,500,000
£4,000,000
£3,500,000
£3,000,000
£2,500,000
£2,000,000
£1,500,000
£1,000,000
£500,000
£0
Ex/non PWID
mild
PWID, mild
Ex/non PWID,
moderate
PWID, moderate
0
100
200
300
Mean incremental QALYs
400
500
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)
Mean incremental costs (£)
Cost-effectiveness efficiency frontiers
– 40% chronic HCV new DAA
£5,000,000
£4,500,000
£4,000,000
£3,500,000
£3,000,000
£2,500,000
£2,000,000
£1,500,000
£1,000,000
£500,000
£0
Ex/non PWID mild
PWID, mild
Ex/non PWID,
moderate
PWID, moderate
0
100
200
300
Mean incremental QALYs
400
500
Cost-effectiveness efficiency frontiers
– 60% chronic HCV new DAA
Ex/non PWID mild
Mean incremental costs £)
£5,000,000
PWID, mild
£4,500,000
£4,000,000
PWID, moderate
£3,500,000
£3,000,000
Ex/non PWID,
moderate
£2,500,000
£2,000,000
£1,500,000
£1,000,000
£500,000
£0
0
100
200
300
Mean incremental QALYs
400
500
ARE CURRENT HCV TREATMENT
RATES SUFFICIENT?
HCV chronic prevalence among PWID (%)
TREATMENT IMPACT IN SEVEN UK CITIES
WITH CURRENT RATES/SVR
Blue: Baseline in 2014
White box: 2024, No scale-up, ITT SVR with IFN/RBV
Bristol
E London
Manchester
Nottingham
Martin NK, JVH 2014
Plymouth
Dundee
N Wales
HCV chronic prevalence among PWID (%)
TREATMENT IMPACT IN SEVEN UK
CITIES WITH SCALE-UP/DAAs
Blue: Baseline in 2014
White box: 2024, No scale-up, ITT SVR with IFN/RBV
Black: 2024, Scale-up to 26/1000 annually with IFN-free DAAs (all genotypes) in 2016
Bristol
E London
Manchester
Nottingham
Martin NK, JVH 2014
Plymouth
Dundee
N Wales
HCV ELIMINATION – MYTH
OR REALITY
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.
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
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