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Management of Patients Co-infected with HCV and HIV: A Close Look at the Role for DAAs. Susanna Naggie, MD Assistant Professor of Medicine Division of Infectious Diseases. Disclosures. Research: Vertex, Anandys, Synexis, Gilead, Merck, BMS
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Management of Patients Co-infected with HCV and HIV: A Close Look at the Role for DAAs Susanna Naggie, MD Assistant Professor of Medicine Division of Infectious Diseases
Disclosures • Research: Vertex, Anandys, Synexis, Gilead, Merck, BMS • Advisory Board: Vertex, Boehringer Ingelheim, Janssen • Speaker: None
HIV & HCV • 10 million people worldwide • 30% of US patients with HIV have HCV Hepatitis C 180 million HIV 40 million Staples CT. Clin Infect Dis 1999
D:A:D Study: Liver-Related Deaths in Persons with HIV 14.5% DAD Study Group, Arch Intern Med 2006 Thein et al. AIDS 2008; 22:1979 DAD Arch Intern Med;2006;166:1632
Treatment • Goal of treatment: • Clinical trial definition • Sustained virologic response • What we tell patients… Cure!
Who to Treat? • Prior response? • Risk stratification • Liver Biopsy • Fibroscan/non-invasive testing • Adherence • Other baseline factors • Race/ethnicity • Genotype 1 subtype
HCV Genome: Polyprotein Moradpour Nature Reviews 2007; 5:453-463
Viral Kinetic Parameters AASLD HCV Treatment Guidelines
PK Interactions: Telaprevir & ART Van Heeswijk et al. CROI 2011 Abstract 119 and ICAAC 2011 Abstract A1-1738a
Study 110 Design: Randomized, Double-blind, Placebo-controlled Trial of Telaprevir SVR T/PR TVR + PR PR Follow-up SVR PR48 (control) Pbo + PR PR Follow-up SVR T/PR TVR + PR PR Follow-up 0 12 24 36 48 60 72 Weeks Stopping/Futility Rules Part A: no ART SVR12 1:1 SVR12 Part B: ART (EFV/TDF/FTC or ATV/r + TDF + FTC or 3TC) SVR12 2:1 SVR12 SVR PR48 (control) Pbo + PR PR Follow-up Dieterich et al. CROI 2012 Abstract 46 Barritt and Fried. Gastro 2012; 142:1314
Study 110: SVR-12 Interim Analysis % of Patients with Undetectable HCV RNA n/N= 5/7 11/16 12/15 28/38 2/6 4/8 4/8 10/22 Dieterich et al. CROI 2012 Abstract 46
PK Interactions: Boceprevir & ART Kasserra et al. 18th CROI 2011 Abstract 118; Hulskotte et al. 19th CROI 2012 Abstract 771LB
Stopping/Futility Rules Randomized, double blind, placebo controlled trial of Boceprevir Weeks 12 24 28 48 72 • Two-arm study, double-blinded for BOC, open-label for PEG2b/RBV • 2:1 randomization (experimental: control) • Boceprevir dose 800 mg TID • 4-week lead-in with PEG2b/RBV for all patients • PEG-2b 1.5 µg/kg QW; RBV 600-1400 mg/day divided BID PEG2b +RBV 4 wk Placebo + PEG2b + RBV 44 wk Follow-up SVR-24 wk Arm 1 PEG2b +RBV 4 wk Boceprevir + PEG2b + RBV 44 wk Follow-up SVR-24 wk Arm 2 Futility Rules Sulkowski et al. CROI 2012 Abstract 47 Barritt and Fried. Gastro 2012; 142:1314
SVR-12 Interim Analysis % of Patients with Undetectable HCV RNA n/N= 3/34 3/64 5/34 27/64 8/34 38/64 11/34 47/64 10/34 42/64 9/34 37/61 Treatment Week Sulkowski et al. CROI 2012 Abstract 47
Adverse Events Telaprevir (TVR) Boceprevir (BOC) Jacobson IM, et al. NEJM, 2011. Poordad F, et al. NEJM, 2011
Phase II/III Studies *Ouwerkerk-Mahadevain 19th CROI Abstract 49
In a nutshell… • Access to DAA is improving • Daily dosing/fewer AEs • FDA approval 1.5 years • IFN-sparing is coming • Assess severity of liver disease • Consider HCV therapy • Treat those who can’t wait OR • Treat those who will be cured • Clinical Trial