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Hepatitis C Virus (HCV) Coinfection: New Drugs, New Strategies

Hepatitis C Virus (HCV) Coinfection: New Drugs, New Strategies. Marion G. Peters, MD John V. Carbone, MD, Endowed Chair Professor of Medicine Chief of Hepatology Research University of California San Francisco. From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. .

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Hepatitis C Virus (HCV) Coinfection: New Drugs, New Strategies

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  1. Hepatitis C Virus (HCV) Coinfection:New Drugs, New Strategies Marion G. Peters, MDJohn V. Carbone, MD, Endowed ChairProfessor of MedicineChief of Hepatology ResearchUniversity of California San Francisco From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.

  2. The Long-Awaited New Era:Protease Inhibitors for HCV Genotype 1 SVR >70% Genotype 1 Response-guided therapy (RGT) Side effects Resistance Drug-drug interactions April 27-28, 2011: FDA Advisory Panel voted 18-0 for approval of boceprevir and telaprevir Both drugs approved by FDA May 2011

  3. 8 7 6 5 4 3 2 1 0 12 Different Types of “Non-Response” Null Relapse HCV RNA (log IU/ml) Breakthrough Partial 24 36 48 60 72 Week of Treatment Adapted from M. Shiffman

  4. EVR: Partial versus CompleteRGT= response guided therapy HCV RNA (log copies/mL) 6 5 eRVR: ud at weeks 4 and 12 4 3 2 ETR SVR RVR cEVR ViralRNA (–) 48 4 12 Wks of Therapy 24 72 0

  5. Similarities/ Differences in Phase III Studies of TVR and BOC in GT1 Naive Mono Pts 1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB-4. ccoptions.com, Zeuzem

  6. Various Paradigms BeingDeveloped Simultaneously • PEG IFN + • Ribavirin + • Single DAA • PIs • Nucs • NS5A • Cyclophilin • antagonist IFN-free regimens PEG IFN + Ribavirin + DAA-1 + DAA-2 • Some trials involve more than one of these designs • PEG IFN lambda being evaluated • Proof of concept for curative potential of IFN-free regimens • had been established

  7. Issues in HCV therapy • Genotype differences • 2 versus 3 versus 1 • 1a poorer response than 1b • Easier to develop resistance • IL28b response • CC versus TT • Prior exposureto IFN and DAA • Extent of liver disease • DDI

  8. HCV and HIV coinfected • Select who to treat • Moderate to severe fibrosis F3-4 • Assess fibrosis • Liver biopsy • Serum tests APRI FIB-4 • Transient elastography • Control HIV • Encourage adherence • Avoid alcohol

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