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

David Wong, Lise Bondy, Alice Tseng, Pauline Murphy, Sharon Walmsley

Disclosures (last 1 year): Educational sessions sponsored by: Abbvie, Gilead

The evolution of HCV in HIV co-infection

Coming to an end

Speaker disclosure

ADDITIONAL TEXT EXAMPLE

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 Board None Principal Investigator in a clinical trial sponsored by a company Gilead: Harvoni for HCV-HIV, Tenofovir for HBV Abbvie: Holkira for HCV (long term follow-up) Research sponsored by a company None 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

5 10 15 20 25 30 35 40 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Hepatology in HIV clinic

PegIFN-RBV PR-BOC PR-TPV SOF-LDV PTV/r-OBV+DSV

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

HIV N=539 +HCV N=293 +HBV N=128

Canadian cohorts

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

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) 165/23/19/24/62 Heavy = 29% 15% active Fibrosis (0-1/2/3/4) 92/46/48/107 F3/4 = 155 (53%) 13% cirrhosis Hepatoma 9 (2.8%) Geno 1/2/3/4 208/20/42/10 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

Treatment over time

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

Fitness of Canadian Cohort with studies

S Saeed et al. Clin Infect Dis 2016;62(7):919

Table 2: HIV characteristics

All N=293 CCC N=874 Median CD4 (range)

436 (<10-1757) 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

48/17/20/11 N=96 (33%) 127/36/20/22 N=205 (23%)

Protease Inhibitors ATZ/DRV/LPV/others

33/40/27/8 N=109 (37%) 164/159/76 N=399 (46%)

Integrase Inhibitors DOL/RAL/EVG

30/49/7 N=86 (29%) 27/190/43 N=260 (30%) 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

10 20 30 40 50 60 70 Pending Failed IFN-Free PI IFN Hepatology in HIV clinic

PegIFN-RBV PR-PI IFN-Free N=15 waiting SVR data

Warehousing * ** * Re-infected * Dead * Transplanted * *** * * ** * * * * *

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 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) 165/23/19/24/62 Heavy = 29% 88/13/14/7/23 Heavy = 20.5% 51/7/2/8/19 Heavy = 31.0% Fibrosis (0-1/2/3/4) 92/46/48/107 F3/4 = 155 (53%) 41/15/25/64 F3/4 = 89 (61%) 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

Who has not had SVR?

N=149 HIV+ anti-HCV+

PCR Neg, 13 Elsewhere, 7 Too late, 29 F0 or F1, 22 Not G1, 8 Not ready, 5 LOST, 58 To start, 5

• 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

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% 31/5/1/17 Heavy = 31% 15% active Fibrosis (0-1/2/3/4) 92/46/48/107 F3/4 = 155 (53%) 21/9/10/11 F3/4=21 (41%) 13% cirrhosis Hepatoma 9 (2.8%) 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