The evolution of HCV in HIV co-infection Coming to an end. David Wong, Lise Bondy, Alice Tseng, Pauline Murphy, Sharon Walmsley

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1 The evolution of HCV in HIV co-infection Coming to an end David Wong, Lise Bondy, Alice Tseng, Pauline Murphy, Sharon Walmsley Disclosures (last 1 year): Educational sessions sponsored by: Abbvie, Gilead

2 Speaker disclosure Potential conflict Disclosure - if potential conflict of interest exists Direct financial interest in a company Investments in a company Membership on a company s Advisory Board Principal Investigator in a clinical trial sponsored by a company Research sponsored by a company ADDITIONAL TEXT EXAMPLE Consultant fees paid by a company None None None Gilead: Harvoni for HCV-HIV, Tenofovir for HBV Abbvie: Holkira for HCV (long term follow-up) None None

3 Background HCV-HIV 1990s: not important (HIV mortality) , 50% deaths from liver disease 2002: Hepatology clinic in Immunodeficiency clinic 2002 PegInterferon-Ribavirin era 2011 Protease inhibitor Sofosbuvir 2014 Interferon free era Public reimbursement May 2015 for F2+ I Bica et al. Clin Infect Dis. 2001;32(3):492

4 Background II Canadian Co-Infection Cohort Prospective study established in 2002 Canada wide 2005 onwards Nov 2015 meeting Proposed prospective study to capture DAA treatment of HCV in HIV Is this study needed or are we too late?

5 Methods I PegIFN-RBV PR-BOC PR-TPV EMR Single person data entry All with HIV, referred for hepatitis C Injection drug use history, not current use Alcohol different thresholds captured Complications of cirrhosis: most did not have gastroscopy Fibrosis assessed by Fibrotest, Fibroscan or Liver biopsy -direct bilirubin if on Atazanavir SOF-LDV PTV/r-OBV+DSV HIV N=539 +HCV N=293 +HBV N= Hepatology in HIV clinic

6 Canadian cohorts MB Klein et al. Int J Epidemiol 2010;39:1162

7 Table 1: Demographics TGH N=293 CCC N=950 Male 256 (87%) 78% White/Black/Asian/ First Nations 243/20/21/9 20% First Nations Med Age (range) 49 (23-78) 45 MSM 188 (64%) 25% IDU 162 (55%) 80% Alcohol (0/1/2/3/4) Fibrosis (0-1/2/3/4) 165/23/19/24/62 Heavy = 29% 92/46/48/107 F3/4 = 155 (53%) Hepatoma 9 (2.8%) Geno 1/2/3/4 208/20/42/10 15% active 13% cirrhosis Failed IFN Rx 79 (24.6%) 14% Alcohol: 0 = min; 1 = 1-2/day; 2 = 2-3/day; 3 = 3-6/day; 4 = >6/day MB Klein et al. Int J Epidemiol 2010;39:1162 S Saeed et al. Clin Infect Dis 2016;62(7):919

8 Treatment over time Warehousing Failed PI IFN Re-infected Dead Transplanted

9 Fitness of Canadian Cohort with studies S Saeed et al. Clin Infect Dis 2016;62(7):919

10 Table 2: HIV characteristics All N=293 CCC N=874 Median CD4 (range) 436 (< ) 500 No ARV 33 (11%) 14% TDF 163 (56%) 318 (36%) ABC 90 (31%) 317 (36%) 3TC or FTC 252 (86%) 635 (73%) Non-Nucs EFV/ETR/NVP/RPV Protease Inhibitors ATZ/DRV/LPV/others Integrase Inhibitors DOL/RAL/EVG 48/17/20/11 N=96 (33%) 33/40/27/8 N=109 (37%) 30/49/7 N=86 (29%) 127/36/20/22 N=205 (23%) 164/159/76 N=399 (46%) 27/190/43 N=260 (30%) S Saeed et al. Clin Infect Dis 2016;62(7):919

11 Methods II Treat all HCV-HIV if access to drugs from 2014 onwards Irrespective of concomitant medications Safety monitoring q2 weeks Blood, urine

12 Treatment over time Hepatology in HIV clinic PegIFN-RBV PR-PI IFN-Free Re-infected Dead Transplanted Warehousing N=15 waiting SVR data Pending Failed IFN-Free PI IFN

13 Safety DILI of SOF/LDV in 3/5 on LPV A Tseng abstract this afternoon Compartment syndrome and renal failure Surgical decompression Renal failure improved on TDF dose reduction Leg improved after SOF/LDV completed

14 Table 1a All N=293 IFN N=146 IFN-free N=87 Male 280 (87.2%) 127 (87.0%) 77 (88.5%) White/Black/Asian/ First Nations 243/20/21/9 128/10/6/1 72/5/7/3 Med Age (range) 49 (23-78) 47 (23-65) 52 (27-74) MSM 188 (64%) 103 (70.5%) 62 (71.3%) IDU 162 (55%) 70 (47.9%) 39 (44.8%) Alcohol (0/1/2/3/4) Fibrosis (0-1/2/3/4) 165/23/19/24/62 Heavy = 29% 92/46/48/107 F3/4 = 155 (53%) 88/13/14/7/23 Heavy = 20.5% 41/15/25/64 F3/4 = 89 (61%) 51/7/2/8/19 Heavy = 31.0% 15/19/18/35 F3/4 = 53 (61%) Hepatoma 9 (2.8%) 5 (3.4%) 2 (2.3%) Geno 1/2/3/4 208/20/42/10 99/14/25/7 84/0/1/2 Failed IFN Rx 79 (24.6%) 98(67.1%) 28 (32.2%) Alcohol: 0 = min; 1 = 1-2/day; 2 = 2-3/day; 3 = 3-6/day; 4 = >6/day

15 Who has not had SVR? N=149 HIV+ anti-hcv+ LOST, 58 Not ready, 5 To start, 5 Not G1, 8 PCR Neg, 13 Elsewhere, 7 Too late, 29 F0 or F1, 22 Transplanted N=2 Both failed IFN-RBV Too sick CA tongue, lung, anal, plasmacytoma, CHF Dead Liver failure 7, Hepatoma 4, Variceal bleed 1, DILI 1, Post transplant sepsis 1 HIV 2, aneurysm 1, Sepsis 1, C diff 1, Renal failure 1, CA Anal, Castleman s

16 Who were lost? All N=293 LOST N=58 CCC N=950 Male 256 (87%) 47 (81%) 78% White/Black/Asian/ First Nations 243/20/21/9 48/5/3/2 20% First Nations Med Age (range) 49 (23-78) 46 (23-65) 45 MSM 188 (64%) 29 (50%) 25% IDU 162 (55%) 39 (67%) 80% Alcohol (0/1/2/3/4) 165/23/19/24/62 Heavy = 29% Fibrosis (0-1/2/3/4) 92/46/48/107 F3/4 = 155 (53%) 31/5/1/17 Heavy = 31% 21/9/10/11 F3/4=21 (41%) Hepatoma 9 (2.8%) 0 Geno 1/2/3/4 208/20/42/10 42/6/7/1 15% active 13% cirrhosis Failed IFN Rx 79 (24.6%) 15 (15.8%) 14%

17 Conclusions Q1: Are we are close to finishing with HCV in HIV at TGH Yes. Warehouse of sick G1s gone F0 and F1s have no access to treatment Waiting for G2, G3, G4. Q2: Are DAAs are safe and effective in HIV coinfection Safety: DILI of SOF/LDV with LPV Effective: only 2 treatment failures to date 3D-R in G1a cirrhotic Childs A SOF/LDV lost last month of meds

18 Caveat This cohort may be more stable than rest of country Adherence was great for most part Experience replicated at St Mike s clinic Resources Clinic nurses Pharmacy in clinic PharmD support ID support

19 Acknowledgements Nurses Pauline, Christine, Angela Alice Tseng, PharmD Pharmacy HIV staff Irv Salit, Sharon Walmsley