Treatment as prevention in HCV: Modelling impact among people who inject drugs and HIV+ men who have sex with men

Transcription

1 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

2 ! DISCLOSURES I have received honoraria to speak at educational sessions and symposia organized by AbbVie, Gilead, and Janssen.

3 ! 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)

4 ! CHANGING HCV TREATMENT LANDSCAPE- INCREASING CURE (SVR) RATES Heim M. Nature Reviews Immunology 2013; 13,

5 ! HIV TREATMENT AS PREVENTION WHAT ABOUT HCV?

6 ! 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

7 Can antiviral treatment play a role in elimination of HCV transmission among people who inject drugs (PWID)?

8 ! 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 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:

9 ! 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:

10 ! 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:

11 ! 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 % 48% East London % 48% Manchester % 56% NoWngham % 44% Plymouth % 37% Tayside/Dundee % 27% North Wales % 33% Defined PWID as on opiate substitution therapy or injected within 3 years Martin NK, et al. Under Review.

12 ! MODELLING TREATMENT IMPACT AMONG PWID IN SEVEN UK CITIES WITH CURRENT RATES AND SVR (PEGIFN/RBV) HCV chronic prevalence among PWID (%) Baseline in , no scale-up, ITT SVR with PEG-IFN + RBV Bristol East London Manchester Nottingham Plymouth Dundee North Wales Martin NK, et al. Under Review.

13 ! MODELLING TREATMENT IMPACT AMONG PWID IN SEVEN UK CITIES WITH SCALE-UP AND DAAS HCV chronic prevalence among PWID (%) Baseline in , 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.

14 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

15 MODELLING PROJECTIONS: MELBOURNE HCV chronic prevalence among PWID IFN-free DAAs Year Martin NK, et al. Hepatology 2013; 55(1):49-57

16 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

17 ! 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.

18 Treatment as prevention: implications for HCV among HIV-infected MSM

19 ! 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 Poster 2. UK CHIC data (unpublished)

20 ! 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 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; P Martin TCS, et al. AIDS 2013;27:

21 ! 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: ; 2. Turner J, et al. J Viral Hepat 2010;17:569 77; 3. Van de Laar T, et al. Gastroenterology 2009;136:

22 ! 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

23 ! 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

24 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)