Clinical and Ethical Issues in Managing HCV Co-Infection Curtis - PowerPoint PPT Presentation

Clinical and Ethical Issues in Managing HCV Co-Infection Curtis Cooper, MD, FRCPC Associate Professor of Medicine University of Ottawa Division of Infectious Diseases

Disclosures • Industry – Investigator: Merck, GS, Abbvie – Consultant /Advisor: Merck, GS, Abbvie – Speaker: Merck, GS, Abbvie • Government – MOH – OHTN – CIHR – CDR – Health Canada – MAC-FI HIV, HCV

HIV-HCV Co-Infection

Case  45 yo HIV-HCV male  Risk Factor- IDU- still active  Used ETOH in the past  now the occasional bender  HIV- Atripla x 6 years  Episodes of treatment interruption but when on ARVs, rarely misses  CD4- 450  HIV RNA- <40

Case  Likely HCV-infected in early 20’s  Genotype 1  HCV RNA 7.8 x 10 5 IU/mL  Received Peg-IFN / RBV in 2007 but interrupted after 6 weeks for poor tolerance and a ‘bender’ (RNA declined by about 2 logs at week 4)  Bx in 2006 suggested stage 2 fibrosis but poor quality and during a period of excess alcohol use  No Fibroscan performed but APRI 1.8

Case  Patient is a daily MJ users and frequently takes ‘liver cleansing’ remedies  Has a longstanding PPI prescription which he uses PRN for GERD

Case  Patient wants therapy now….  Key questions:  What are the DAA treatment options?  What are the DDI concerns?  What is the best fibrosis assessment modality?  What about re-infection risk?  Are HCV treatment outcomes really as good in HIV- HCV co-infection as they are in HCV mono-infection?

Canadian HIV/Hepatitis C Management and Treatment Guidelines CIHR CANADIAN HIV TRIALS NETWORK (CTN) • Similar mx in HIV-HCV as HCV mono-infection • Anticipated SVR rates in HIV-HCV co-infection are similar to HCV mono-infection with interferon- free, DAA regimens • Carefully evaluate for DDIs before and during treatment • Select ARVs in anticipation of subsequent HCV DAA treatment • Discuss harm reduction strategies in those at risk for HCV exposure Active injection drug use • MSM •

Key Co‐Infection Regimens • • Sofosbuvir + daclatasvir Grazoprevir + elbasvir (ALLY‐2) (N=203) 1 (C‐EDGE) (n=218) 2 Treatment-naive Treatment- Adapted from experienced 1. Levin J, et al. Presented at EASL 2015; Poster #P1353. 2. Rockstroh JK, et al. Presented at EASL 2015; Poster #P0887.

ION‐4 Overall Overall Naïve vs Experienced Cirrhosis Status SVR12 (%) 258/268 63/67 321/335 142/150 179/185 HCV Rx HCV Rx No Cirrhosis Cirrhosis Overall Experienced Naïve 10 Error bars represent 95% confidence intervals. Naggie S, et al. ION-4 Study. NEJM 2015

‡ ASTRAL-5 HIV/HCV Coinfection Study Results: SVR12 by Cirrhosis or Prior Treatment 100 97 94 97 94 93 100 95 80 SVR12 (%) 60 40 20 101 82 19 71 30 45 56 106 87 19 75 31 48 58 0 Non‐ Treatment Treatment Black Non‐black Total Cirrhotics cirrhotics Naïve Experienced High SVR12 achieved in HIV‐coinfected patients regardless of cirrhosis status and treatment experience † Patients LTFU were incarcerated, one patient on Day 1 and one patient on Week 4 Error bars represent 95% confidence intervals. 12 Brau, IAS, 2016; Data on File, Gilead Sciences.

Drug-Drug Interactions between HCV DAAs and HIV Antiretrovirals 13

Impact of DAA Regimens on Co-Infection Guidelines  Priority shifts from early HIV treatment to early HCV treatment  Fewer contraindications for HCV treatment  Target populations for HCV antiviral tx is expanded  Issues related to DDI reduced  Benefits for Patient-Health Care Team relationship  Increased network of HCV treaters

Barriers  Concentration of Barriers to Engagement and Treatment Success  Socioeconomic  Mental Health  Substance Abuse  Stigma  Diverse populations within the HIV community

Research Needs  Non-Genotype 1 Treatment  Treatment of HIV-HCV co-infection in more advanced disease  RGT  HCV treatment post OLT

HIV-HCV Management Conclusions  Gap in SVR has been bridged  Safety and tolerability issues eliminated  Tx issues not unique to HIV-HCV  Same general approach to work-up, treatment and long-term follow-up

Discussion