Treatment as prevention in HCV: Modelling impact among people who inject drugs and HIV+ men who have sex with men Natasha Mar)n, Peter Vickerman, Ma/ Hickman School of Social and Community Medicine, University of Bristol
! DISCLOSURES I have received honoraria to speak at educational sessions and symposia organized by AbbVie, Gilead, and Janssen.
! ELIMINATING HCV: NEED TO TARGET THOSE AT RISK OF TRANSMISSION Elimination: Reducing incidence of new infections to zero in a local region In many developed and developing country settings with injecting drug use, people who inject drugs (PWID) are the core of the HCV epidemic Contribute >90% new infections in the UK New epidemic of HCV among HIV + men who have sex with men (MSM)
! CHANGING HCV TREATMENT LANDSCAPE- INCREASING CURE (SVR) RATES Heim M. Nature Reviews Immunology 2013; 13, 535-542.
! HIV TREATMENT AS PREVENTION WHAT ABOUT HCV?
! TALK OUTLINE Can we eliminate HCV transmission and reduce HCV prevalence to negligible levels among PWID? Implications for treatment as prevention among HIV+ MSM and preliminary modelling
Can antiviral treatment play a role in elimination of HCV transmission among people who inject drugs (PWID)?
! HCV TREATMENT EFFECTIVE FOR PWID, BUT FEW TREATED Despite evidence that PWID achieve similar SVR rates as non/ex-pwid 1 3 And despite small-scale studies reporting low re-infection rates among PWID 1,4,5 Figure taken from Grebely & Dore, Antiviral Research 2014. 1. Aspinall EJ, et al. Clin Infect Dis 2013;57(Suppl 2):S80 9; 2. Dimova RB, et al. Clin Infect Dis 2013;56:806 16; 3. Hellard M, et al. Clin Infect Dis 2009;49:561 73; 4. Dalgard O. Clin Infect Dis 2005;40(Suppl 5):S336 8; 5. Grebely J, et al. J Gastroenterol Hepatol 2010;25:1281 4.
! NEED DYNAMIC TRANSMISSION MODEL TO ASSESS IMPACT OF TREATMENT ON PREVALENCE/INCIDENCE New injectors Susceptible Susceptible (treated) At risk of re-infection Non-SVR infected Treatment Chronically infected Cease/die Infection risk related to prevalence Acutely infected Martin NK, et al. Hepatology 2013; 55(1):49-57 Martin NK, et al. J Hep 2011; 54:1137-44
! MODELLING HCV TREATMENT AS PREVENTION AMONG PWID: HCV RELATIVE PREVALENCE REDUCTIONS AT 10 YEARS WITH PEGIFN+RBV Martin NK, et al. J Hep 2011; 54:1137-44
! CURRENT HCV TREATMENT RATES AMONG PWID: 4-FOLD DIFFERENCE IN UK SITES SITE PWID Popula.on Es.mate (min, max) HCV chronic prevalence (min, max) PWID HCV Treatments per year Rate per 1000 PWID (min, max) Bristol 3200 4400 37% 48% 18 4.1 5.6 East London 2400 6000 37% 48% 25 4.2 10.4 Manchester 2300 4000 48% 56% 63 15.8 27.4 NoWngham 1300 2500 37% 44% 32 12.8 24.6 Plymouth 1100 2000 30% 37% 17 8.5 15.5 Tayside/Dundee 2000 3000 20% 27% 34 11.3 17.0 North Wales 1700 3400 27% 33% 18 5.3 10.6 Defined PWID as on opiate substitution therapy or injected within 3 years Martin NK, et al. Under Review.
! MODELLING TREATMENT IMPACT AMONG PWID IN SEVEN UK CITIES WITH CURRENT RATES AND SVR (PEGIFN/RBV) HCV chronic prevalence among PWID (%) 100 90 80 70 60 50 40 30 20 10 0 Baseline in 2014 2024, no scale-up, ITT SVR with PEG-IFN + RBV Bristol East London Manchester Nottingham Plymouth Dundee North Wales Martin NK, et al. Under Review.
! MODELLING TREATMENT IMPACT AMONG PWID IN SEVEN UK CITIES WITH SCALE-UP AND DAAS HCV chronic prevalence among PWID (%) 100 90 80 70 60 50 40 30 20 10 0 Baseline in 2014 2024, no scale-up, ITT SVR with PEG-IFN + RBV 2024, scale-up to 26/1000 annually with IFN-free DAAs (all genotypes) in 2016 Bristol East London Manchester Nottingham Plymouth Dundee North Wales Martin NK, et al. Under Review.
MODELLING PROJECTIONS: TOWARDS ELIMINATION IN EDINBURGH WITH DAA THERAPY HCV chronic prevalence among PWID Year IFN-free DAAs Martin NK, et al. Hepatology 2013; 55(1):49-57
MODELLING PROJECTIONS: MELBOURNE HCV chronic prevalence among PWID IFN-free DAAs Year Martin NK, et al. Hepatology 2013; 55(1):49-57
BUT IS IT AFFORDABLE??? EDINBURGH PROJECTIONS HCV chronic prevalence among PWID 168 treatments/yr at 35,000/treatment = 5.9m (~7.1m EUR) ANNUALLY Year Martin NK, et al. Hepatology 2013; 55(1):49-57
! 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 Scale-up of harm reduction reduces numbers needed to treat AND prevents transmission/reinfection Martin NK, et al. Clinical Infectious Diseases 2013;57(suppl 2): S39-S45.
Treatment as prevention: implications for HCV among HIV-infected MSM
! TREATMENT AS PREVENTION AMONG HIV+ MSM: A UNIQUE OPPORTUNITY? HCV + PWID HIV + /HCV + MSM Population size Large Small compared with PWID HCV prevalence Routine testing and HCV treatment integrated with other treatment settings Heterogeneous, but can be high (>60%) Poor/evolving Next-generation DAA SVR High High Relatively low (~7%) Good in many developed country settings (~50% treatment experienced in Berlin 1 & UK 2 ) Evidence for other prevention/behaviour change interventions International transmission network Reinfection rate Good (opiate substitution therapy, needle/syringe programmes) Probably minimal in most settings Appears lower than primary incidence Poor High Appears higher (5-10x) than primary incidence 1. Albus S et al. Low rates of treatment despite high rates of significant fibrosis: a five year single center experience from Berlin. C-HEP Congress Berlin 2014. Poster 2. UK CHIC data (unpublished)
! High incidence of HCV re-infection among HIV + MSM! in Re-infection European AIDS an Treatment alarming Network reality! (NEAT) Further re-infections 553 patients from 7 NEAT centres with cured acute HCV since 2001 141 with at least one re-infection (25.5%) 1509 patient years of follow-up; median 2.1 years Reinfection incidence rate: 7.82/100 patient years 1. Ingiliz P et al, Spontaneous clearance rates increase with HCV reinfection episode in HIV-positive men who have sex with men (MSM) independent of HCV subtype. EASL 2014; P781 2. Martin TCS, et al. AIDS 2013;27:2551 7.
! DYNAMIC MODEL OF HCV AMONG HIV+ MSM IN UK Extended previous dynamic transmission model with stratification by Risk (high/low risk) Year of diagnosis (1, 2, 3, 4+) with differential treatment rates Treatment by acute or chronic stage Calibrated to UK data HCV prevalence among HIV+ MSM [UK CHIC] HCV primary and reinfection incidence [Public Health England data, Chelsea & Westminster Hospital/NEAT] HCV diagnosis rates and treatment rates by stage (acute/chronic) and year of diagnosis (1, 2, 3, 4+) [UK CHIC] 1. Rockstroh JK, et al. J Infect Dis 2005;192:992 1002; 2. Turner J, et al. J Viral Hepat 2010;17:569 77; 3. Van de Laar T, et al. Gastroenterology 2009;136:1609 17.
! CONCLUSIONS: HCV PREVENTION STRATEGIES FOR ELIMINATION Existing levels of HCV treatment, even in the DAA era, are likely to have minimal impact on reducing HCV transmission and prevalence/ incidence to negligible levels among PWID or HIV+ MSM However, scale-up of HCV treatment could reduce HCV incidence and prevalence to negligible levels Among PWID in combination with harm reduction (OST and NSP) Among HIV+ MSM in the UK, if target all and not just recent diagnoses But is treatment as a public health prevention strategy affordable at current prices??? Need European bulk buying to support treatment as prevention
! LIMITATIONS/FUTURE WORK Theoretical modelling projections- no empirical data treatment can reduce HCV prevalence MSM projections preliminary; neglect network effects and migration/travel; need better epidemiological and behavioural data Need modelling to assess treatment scale-up and targeting to optimise BOTH prevention of HCV transmission and reduction of ESLD Need more cost-effectiveness evaluations of HCV screening/case-finding and treatment programmes among high risk groups, including prevention benefits Dynamic models needed to determine local and national targets
ACKNOWLEDGEMENTS Bristol: Ma/hew Hickman, Peter Vickerman LSHTM: Alec Miners Health Protec)on Scotland: Sharon Hutchinson, David Goldberg Queen Mary s London: Graham Foster UK PWID projec)ons: John F Dillon, Fiona Gordon, Javier Vilar, Amanda Clements, Ma/hew Cramp, Stephen Ryder, Heather Lewis, Andrew Us_anowski, Daniela DeAngelis, Will Irving, Vivian Hope, Noel Craine, Marion Lyons Australia PWID projec)ons: Margaret Hellard, Gregory J Dore, Jason Grebely Canada PWID projec)ons: Viviane Dias Lima MSM projec)ons: Caroline Sabin, Alicia Thornton, Sam LaWmore, Valerie Delpech, Mark Nelson, Thomas Mar_n, Graham Cooke FUNDERS: Na_onal Ins_tute for Health Research (NIHR) Postdoctoral Fellowship Health Protec_on Scotland, Medical Research Council (MRC)