1. Slide 1 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA Marion G. Peters, MD John V. Carbone, MD, Endowed Chair Professor of Medicine Chief of Hepatology Research University of California San Francisco Hepatitis C Virus (HCV) Coinfection: New Drugs, New Strategies From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.

2. Slide 2 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. The Long-Awaited New Era: Protease Inhibitors for HCV Genotype 1 SVR >70% Genotype 1 Response-guided therapy (RGT) Side effectsResistance April 27-28, 2011: FDA Advisory Panel voted 18-0 for approval of boceprevir and telaprevir Both drugs approved by FDA May 2011 Drug-drug interactions

3. Slide 3 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. 2436486072 Week of Treatment HCV RNA (log IU/ml) Different Types of “Non-Response” Null Partial Breakthrough Relapse Adapted from M. Shiffman

4. Slide 4 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. 72 4 48 Viral RNA (–) 0 1224 EVR: Partial versus Complete RGT= response guided therapy Wks of Therapy HCV RNA (log copies/mL) 6 cEVR 5 4 3 2 RVR eRVR: ud at weeks 4 and 12

5. Slide 5 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. Similarities/ Differences in Phase III Studies of TVR and BOC in GT1 Naive Mono Pts ParameterTVR [1] BOC [2] PR lead-in?NoYes: 4 wks PegIFN alfa formulation2a2b PI dosing requirements TID; administer with fatty meal TID with food not low fat Duration of PI triple therapy 8-12 wks followed by 12-40 wks PR 24-44 wks after 4 wks PR lead-in Qualification for shortened therapy (response guided) Undetectable HCV RNA Wk 4 and 12 of triple therapy Undetectable HCV RNA w8 and w24 of triple therapy Qualified for shortened therapy, % 58 (24 wks)44 (28 wks) SVR, %69-7563-66 Relapse, %99 Adverse events more frequent in PI arms Rash, anemia, pruritus, nausea Anemia, dysgeusia 1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB-4. ccoptions.com, Zeuzem

6. Slide 6 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. Various Paradigms Being Developed Simultaneously PEG IFN + Ribavirin + Single DAA PIs Nucs NS5A Cyclophilin antagonist PEG IFN + Ribavirin + DAA-1 + DAA-2 IFN-free regimens 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. Slide 7 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. 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 exposure to IFN and DAA Extent of liver disease DDI

8. Slide 8 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. 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