HCV screening in Australia What we do now, and what we hope to do in future? Professor Gregory Dore

Transcription

1 HCV screening in Australia What we do now, and what we hope to do in future? Professor Gregory Dore

2 Disclosures Research grants, travel support, and honoraria: AbbVie, Gilead, Merck

3 HCV screening in Australia The national HCV screening program HCV testing algorithm Strategies to enhance HCV screening and linkage to care New HCV diagnostic technologies

4 National Strategies and Partnership Government, Academic, Clinical, Civil Society collaborations (Accessed July 2016); (Accessed July 2016)

5 Australian Consensus Guidelines on HCV Management Key features of HCV screening program: National HCV testing policy for >15 years Risk-based approach High levels of screening Free HCV testing Approx. 80% estimated to be HCV antibody diagnosed But, only 50% HCV RNA confirmed Vast majority in three high-risk groups

6 Australian HCV Care cascade: end , , ,000 81% 175, , , ,000 75,000 50,000 25,000 47% 14% of those with chronic HCV at start of 2016 received treatment. Of those treated 93% were cured. - Living with chronic hepatitis C Diagnosed with chronic hepatitis C Hepatitis C RNA tested Received treatment in 2016 Cured in 2016 Kirby Institute, Annual Surveillance Report 2017

7 HCV screening algorithm: too complicated + negative 1 SCREEN: HCV antibody test Eg. m2000 ARCHITECT + 2 SUPPLEMENTAL antibody test: Confirm HCV antibody result Second method (eg. ELISA) Exclude false positive result Nucleic acid RNA: Confirm active infection Quantitative RNA recommended Core antigen is approved (not used) Genotype 5 Treat Adapted from National Hepatitis C Testing policy, 2017

8 Too many steps and visits to an HCV diagnosis Visit #1 Visit #2 Visit #3 Visit #4 Visit #5 Central Lab Central Lab Anti-HCV antibody (Physician) Phlebotomy (Phlebotomist) Antibody test 1-2 weeks Receive diagnosis (Physician) Phlebotomy (Phlebotomist) RNA test 1-2 weeks Receive diagnosis (Physician) Grebely J, Applegate TA, Cunningham P, Feld JJ. Exp Rev Mol Diag 2017

9 (%) HCV antibody testing with reflex RNA testing Central Lab Order anti-hcv antibody with reflex HCV RNA (Physician) 100% 100% 74% (100% of Ab+) Phlebotomy (Phlebotomist) RNA test 1-2 weeks Receive diagnosis (Physician) 100% 56% 51% (92% of referred) HCV Ab+ Sena Public Health Rep RNA Tested HCV RNA+ HCV RNA+ Referred 1 st appoint

10 Advances in diagnostics and point-of-care testing Rapid diagnostic tests Dried blood spot testing Point of care and random access HCV RNA testing Fourati S, et al. INHSU 2017, New York, United States, September 6-8, 2017

11 Rapid HCV antibody testing Central Lab Rapid anti-hcv antibody test (Health care worker) Phlebotomy (Phlebotomist) RNA test 1-2 weeks Receive diagnosis (Physician) Single-center free testing clinic People randomized to interventions for testing of HIV, HBV, and HCV Standard serologybased testing (n=162) Point-of-care rapid testing (n=162) Aware of status 64% (n=104) P< % (n=159) Linked to care 60% P= % Bottero J Open Forum Inf Dis 2017

12 Dried blood spot testing Central Lab Antibody and RNA testing Dried blood spot sample (Health care worker) Receive diagnosis (Physician) Advantages Disadvantages 1) Enhances HCV testing and linkage to care 1) Still requires centralized testing 2) Avoids need for phlebotomy 2) Requires 2 nd visit to get result 3) Enables reflex virological testing 3) Sometimes requires multiple pricks 4) Stable, easy to transport and store 4) May yield a lower HCV RNA titer 5) Can be used for other purposes (e.g. HIV) 6) Collection by peers or community workers Grebely J, Applegate TA, Cunningham P, and Feld JJ Exp Rev Mol Diag 2017

13 Finger-stick testing for HCV RNA detection 60 mins Relatively easy-to-use point-of-care HCV RNA test GeneXpert in many LMIC Real-world performance for HCV RNA quantification very good Venepuncture HCV Viral Load Sensitivity 99%, Sensitivity 96% 1 Modified finger-stick assay Sensitivity 98%, Sensitivity 99% 2 Xpert HCV Viral Load Fingerstick - Sensitivity 100%, Sensitivity 100% 3 One step closer to a single-visit diagnosis (needs to be more rapid ) McHugh J Clin Micro 2017; Grebely J, et al. Lancet Gastro Hep 2017; Lamoury GF, et al. J Infect Dis 2018

14 The potential role of HCV core antigen testing Diagnosis chronic HCV Non-responder Responder DAA 4wk 8wk EOT PTW12 PTW24 HCV core antigen Core protein Abbott ARCHITECT i2000r Diagnosis of chronic HCV infection Correlates with RNA > 3,000 IU/ml Identifies responders 12 weeks post tx Sensitivity >93.4% (CI %) Specificity >98.8% (CI %) 14 Freiman et al. Ann Intern Med 2016; Chevaliez. Antiviral Therapy 2016

15 The potential role of HCV core antigen testing Chronic HCV Recent HCV lo g fm o l/l / lo g IU /m l a b c lo g fm o l/l / lo g IU /m l lo g fm o l/l / lo g IU /m l 0 E v e n t w k (fr o m B S L ) E v e n t w k (fr o m B S L ) E v e n t w k (fr o m B S L ) lo g fm o l/l / lo g IU /m l d e f lo g fm o l/l / lo g IU /m l lo g fm o l/l / lo g IU /m l E v e n t w k (fr o m B S L ) E v e n t w k (fr o m B S L ) E v e n t w k (fr o m B S L ) Lamoury J, et al. J Clin Virol 2017

16 Moving to a single-visit hepatitis C diagnosis Grebely J, et al Exp Rev Mol Diag 2017

17 Need to move towards simplified models of HCV care Testing at pre-treatment and SVR12 only Qualitative HCV RNA or core Ag Preferably simple (e.g. fingerstick), rapid, POC Ongoing monitoring if risk of HCV reinfection Modified from John Dillon

18 Traditional referral model of HCV testing and treatment Sexual health Tertiary care hospital Community health centres Drug and alcohol clinics Prisons Primary health care / GPs Needle and syringe programmes Pharmacies

19 Redefining models of HCV testing and linkage to care Sexual health Tertiary care hospital Community health centres Drug and alcohol clinics Prisons Primary health care / GPs Needle and syringe programmes Pharmacies

20 Acknowledgements UNSW Sydney Dr Tanya Applegate A/Prof. Jason Grebely Mr. Francois Lamoury A/Prof. Gail Matthews Prof. Andrew Lloyd Dr. Behzad Hajarizadeh Dr. Maryam Alavi Dr. Marianne Martinello Ms. Pip Marks Dr. Richard Gray Dr. Amy Known Prof. Lisa Maher Dr. Jenny Iversen Collaborators Prof. Margaret Hellard (Australia) Dr. Joe Doyle (Australia) Prof. Alex Thompson (Australia) Prof. Jacob George (Australia) Prof. Ed Gane (New Zealand) A/Prof. Natasha Martin (USA) Prof. Peter Vickerman (UK) Prof. Matt Hickman (UK) Dr. Homie Razavi (USA) Dr. Philip Bruggmann (Switzerland) Prof. Olav Dalgard (Norway) Prof. Julie Bruneau (Canada) Dr. Jordan Feld (Canada)