Pauline Murphy, Sharon Walmsley Disclosures (last 1 year): - PowerPoint PPT Presentation

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

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

Background • HCV-HIV – 1990s: not important (HIV mortality) – 1998-1999, 50% deaths from liver disease – 2002: Hepatology clinic in Immunodeficiency clinic • 2002 PegInterferon-Ribavirin era • 2011 Protease inhibitor 1.0 • 2013 Sofosbuvir • 2014 Interferon free era – Public reimbursement May 2015 for F2+ I Bica et al. Clin Infect Dis. 2001;32(3):492

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?

Methods I 40 PR-BOC SOF-LDV PegIFN-RBV PR-TPV PTV/r-OBV+DSV 35 EMR 30 Single person data entry HIV N=539 25 All with HIV, referred for hepatitis C +HCV N=293 Injection drug use history, not current use +HBV N=128 20 Alcohol – different thresholds captured Complications of cirrhosis: most did not have gastroscopy 15 Fibrosis assessed by Fibrotest, Fibroscan or Liver biopsy -direct bilirubin if on Atazanavir 10 Hepatology in HIV clinic 5 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

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

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

Treatment over time 25 Warehousing ** 20 * 15 * Failed * PI * 10 IFN *** * ** 5 * Re-infected * * * Dead * * * * Transplanted 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

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

Table 2: HIV characteristics All CCC N=293 N=874 436 (<10-1757) 500 Median CD4 (range) No ARV 33 (11%) 14% TDF 163 (56%) 318 (36%) ABC 90 (31%) 317 (36%) 252 (86%) 635 (73%) 3TC or FTC 48/17/20/11 127/36/20/22 Non-Nucs N=96 (33%) N=205 (23%) EFV/ETR/NVP/RPV Protease Inhibitors 33/40/27/8 164/159/76 N=109 (37%) N=399 (46%) ATZ/DRV/LPV/others 30/49/7 27/190/43 Integrase Inhibitors N=86 (29%) N=260 (30%) DOL/RAL/EVG S Saeed et al. Clin Infect Dis 2016;62(7):919

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

Treatment over time 70 PegIFN-RBV PR-PI IFN-Free 60 N=15 waiting SVR data 50 * Re-infected * Dead Pending Warehousing 40 * Transplanted Failed 30 IFN-Free PI Hepatology in HIV clinic ** 20 IFN * * * 10 * * *** * ** * * * 0

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

Table 1a All IFN IFN-free N=293 N=146 N=87 280 (87.2%) 127 (87.0%) 77 (88.5%) Male White/Black/Asian/ 243/20/21/9 128/10/6/1 72/5/7/3 First Nations 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 165/23/19/24/62 88/13/14/7/23 51/7/2/8/19 (0/1/2/3/4) Heavy = 29% Heavy = 20.5% Heavy = 31.0% Fibrosis 92/46/48/107 41/15/25/64 15/19/18/35 (0-1/2/3/4) F3/4 = 155 (53%) F3/4 = 89 (61%) 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

Who has not had SVR? N=149 HIV+ anti-HCV+ • Transplanted N=2 PCR Neg, – Both failed IFN-RBV To start, 5 13 Elsewhere, • Too sick 7 – CA tongue, lung, anal, plasmacytoma, CHF • Dead LOST, 58 Too late, 29 – 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, F0 or F1, 22 CA Anal, Castleman’s Not ready, Not G1, 8 5

Who were lost? All LOST CCC N=293 N=58 N=950 256 (87%) 47 (81%) 78% Male White/Black/Asian/ 243/20/21/9 48/5/3/2 20% First Nations 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 31/5/1/17 15% active Heavy = 29% Heavy = 31% Fibrosis 92/46/48/107 21/9/10/11 13% cirrhosis (0-1/2/3/4) F3/4 = 155 (53%) F3/4=21 (41%) Hepatoma 9 (2.8%) 0 Geno 1/2/3/4 208/20/42/10 42/6/7/1 Failed IFN Rx 79 (24.6%) 15 (15.8%) 14%

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 co- infection – 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

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

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