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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