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Hepatitis C: From Diagnosis to Treatment and Co-Infection with HIV Presented by: Amanda Birnschein Preceptor: Dr. Schafer, PharmD Rotation: APPE 2 – Ambulatory.

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Presentation on theme: "Hepatitis C: From Diagnosis to Treatment and Co-Infection with HIV Presented by: Amanda Birnschein Preceptor: Dr. Schafer, PharmD Rotation: APPE 2 – Ambulatory."— Presentation transcript:

1 Hepatitis C: From Diagnosis to Treatment and Co-Infection with HIV Presented by: Amanda Birnschein Preceptor: Dr. Schafer, PharmD Rotation: APPE 2 – Ambulatory Care Infectious Disease

2 Guess What Today Is?..... World Hepatitis Day! Centers for Disease Control and Prevention. Available at: http://www.cdc.gov. Accessed July 25, 2014.

3 Background

4 What is Hepatitis C? Contagious liver disease that stems from HCV and ranges in severity Centers for Disease Control and Prevention. Hepatitis C information for health professionals. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014. Mild illness lasting a few weeks  serious, lifelong illness that attacks the liver

5 Pop Quiz: Epidemiology What is the prevalence of chronic HCV infection in the United States? a)~ 99,000 b)~ 3.2 million c)~ 6 million d)~ 1 billion Centers for Disease Control and Prevention. Hepatitis C information for health professionals. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014.

6 Epidemiology: HCV An estimated 3.2 million persons in the United States have chronic HCV Most people do not know they are sick Most prevalent among those born during 1945 – 1965 Infected in the ’70s and ‘80s when rates were the highest Only 849 cases of confirmed acute HCV were reported in 2007 ~17,000 new infection occurred that year In 2007, there were 15,106 deaths caused by HCV HCV is the most common blood-borne pathogen Centers for Disease Control and Prevention. Hepatitis C information for health professionals. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014.

7 Epidemiology: HCV Co- infection with HIV ~ ¼ of HIV-infected individuals in U.S. are also infected with HCV Co-infection is higher (~80%) among IV drug users since both infections are passed through the blood HCV progresses more rapidly in HIV infected individuals More than triples the risk for liver disease, liver failure, and liver- related death from HCV Liver disease has become the leading cause of non-AIDS related deaths in the HIV population Centers for Disease Control and Prevention. HIV and Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/Populations/PDFs/HIVandHep- FactSheet.pdf. Accessed July 27, 2014.

8 HCV & HIV Co-infection: Increased Risk of Death Branch AD, et al. CID. 2012;55:137-144.

9 Pop Quiz: HCV Cell Life Cycle What is one major difference in terms of cell life cycle that is different between HCV and HIV? a)The HCV does not need to enter the liver cell in order to replicate b)HCV does not have budding of an immature virus c)HCV does not have reverse transcriptase step in the life cycle, leading to no integration into the nucleus d)There are no major differences, HCV and HIV have the same life cycle

10 HCV Life Cycle ① Viral attachment and entry ② Fusion and viral RNA Release ③ Translation and production of polyprotein precursors ④ Cleavage of polyprotein into functional and structural proteins ⑤ Formation of the RNA replication complex ⑥ RNA replication ⑦ Viral assembly, budding, and release The AIDS InfoNet. Available at: http://www.aidsinfonet.org/fact_sheets/view/670. Accessed: July 25, 2014

11 Patient Case

12 HPI: A 36 YOM referred to the liver clinic by his primary care physician for assessment of his abnormal liver enzymes. Patient has been noticing that he is fatigued and has had a decrease in his appetite. Until his primary care appointment, he didn’t realize that he lost 13 pounds over the past two months. He does not have any past history of liver problems. PMH: GERD, Seasonal allergies, IV drug use during late teens FM: No known family history of liver problems. Parents died in car accident 18 years ago. SH: Married for 11 years; one child aged six years old. Non-smoker, denies illicit drug use, social drinker 1-2 times per week with approximately 2-3 beers at a time. He currently works as a phlebotomist at a local hospital. ROS: Non-specific symptoms such as fatigue and weight loss, but denies any other symptoms of liver disease. Meds: Omeprazole 20 mg PO daily, loratadine 10 mg PO daily PRN seasonal allergies

13 VS: BP 110/72, P 70, RR 17, T 37.0 C, Wt 168 lbs, Ht 5’11” Skin: no jaundice HEENT: PEERLA, EOMI, sclera anicteric Abd: No hepatomegaly or splenomegaly present. No evidence of ascites. Extremities: No edema, normal ROM Neuro: A&O x 3, CN II-XII intact Labs (obtained during PCP visit): AST 186 IU/L ALT 197 IU/L T bili 1.5 mg/dL Alb 3.5 g/dL HIV (-) HBsAg (-) Angi-HAV (-) Anti-HCV (+) HCV RNA 4.6 million copies/mL PT 12.5 sec Liver biopsy today: moderate degree of fibrosis and inflammation consistent with chronic hepatitis

14 Risk Behaviors Most common methods to become infected Sharing needles, syringes, or other equipment to inject drugs Intranasal illicit drug use Less commonly Sharing personal care items that may have come in contact with blood, such as razors or toothbrushes Have sexual contact with a person infected with HCV American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014. Centers for Disease Control and Prevention. Hepatitis C information for health professionals. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014.

15 Risk Exposures Long-term hemodialysis Getting a tattoo in an unregulated setting Healthcare, emergency medical, and public safety workers after needle sticks, sharps, or mucosal exposures to HCV-infected blood Children born to HCV-infected women Prior recipients of transfusions or organ transplants, including persons who: Were notified they received blood from someone who later tested positive Blood transfusion or organ transplant before July 1992 Received clotting factor concentrates produced before 1987 Were ever incarcerated Other Medical Conditions HIV infection Unexplained chronic liver disease and chronic hepatitis American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

16 Symptoms Pain in the right upper abdomen Abdominal swelling due to fluid (ascites) Clay-colored or pale stools Dark urine Joint pain FatigueFeverItchingJaundice Loss of appetite nausea and vomiting PubMed health. Hepatitis C. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001329/. Accessed July 25, 2014. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014.

17 Who Should be Tested? HCV testing is recommended in select populations based on: Demography Primary exposures High-risk behaviors Medical conditions 1.At least once for persons born between 1945 and 1965 1.Annual testing: a.Person who inject drugs b.HIV-seropositive men who have unprotected sex with men 2.Periodic testing to persons with ongoing risk factors for exposure to HCV American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

18 Diagnosis * Exposure within the past 6 months, testing for HCV RNA or follow-up testing for HCV antibody should be performed * Those that are immune compromised, testing for HCV RNA should be performed † To differentiate past, resolved HCV infection from biologic false positivity for HCV antibody, testing with another HCV antibody assay can be considered American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

19 What is missing for MJ’s diagnosis? Genotype! Guidelines recommend: Testing for HCV genotype to guide selection of the most appropriate antiviral There are at least 6 different HCV genotypes with over 50 different subtypes Genotype 1 is the most common in the United States Treatment varies depending on genotype Determines likelihood of treatment response and duration of treatment Centers for Disease Control and Prevention. Hepatitis C information for health professional. Available at: http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed July 25, 2014.

20 Genotypes in the World Center for Disease Analysis. Hepatitis C. Available at: http://www.centerforda.com/Maps/World%20P.jpg. Accessed July 26, 2014.

21 Genotype in the United States Center for Disease Analysis. Hepatitis C. Available at: http://www.centerforda.com/Maps/World%20P.jpg. Accessed July 26, 2014.

22 MJ and Genotype MJ has his genotype tested and finds out he has genotype 1a Mini Pop Quiz: Anything else we could ultimately to test for? 1)Q80K polymorphism 2)IL-28B gene 3)K103N mutation 4)Blood sugar 5)1 & 2 6)All of the above

23 Non-Pharm Recommendations Persons with current HCV infection should: Abstain from alcohol Be tested for HBV and HIV infections Evaluation for advanced fibrosis Liver biopsy, imaging, or non-invasive markers Vaccination against HAV and HBV Education on how to avoid HCV transmission to others American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

24 Guidelines & HCV Treatment: SofosbuvirSimeprevirRibavirinPEG-interferon

25 Previously in HCV Guidelines Peginterferon alfa-2a 180 mcg/wk OR Peginterferon alfa-2b 1.5 mcg/kg/wk + Ribavirin 1000mg (Wt <75 kg) OR Ribavirin 1200mg (Wt >75 kg) + Telaprevir OR Boceprevir Genotype 2 or 3 Treatment Peginterferon alfa-2a 180 mcg/wk OR Peginterferon alfa-2b 1.5 mcg/kg/wk Genotype 1 Treatment + Ribavirin 800mg Ghany MG, et al. Hepatology. 2011;54(4):1433-1444.

26 HCV Treatment Overview: Treatment Naïve Patients GenotypeRecommended Regimen 1IFN Eligible SOF + RBV + PEG x 12 weeks IFN Ineligible SOF + SMV + RBV x 12 weeks 2SOF + RBV x 12 weeks 3SOF + RBV x 24 weeks 4IFN Eligible SOF + RBV + PEG x 12 weeks IFN Ineligible SOF + RBV x 24 weeks 5 or 6SOF + RBV + PEG x 12 weeks SOF = sofosbuvir RBV = ribavirin PEG = peginterferon SMV = simeprevir American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

27 HCV Treatment Overview: Nonresponders GenotypeRecommended Regimen 1SOF + SMV + RBV x 12 weeks 2SOF + RBV x 12 weeks 3SOF + RBV x 24 weeks 4SOF + RBV + PEG x 12 weeks OR SOF + RBV x 24 weeks 5 or 6SOF + RBV + PEG x 12 weeks SOF = sofosbuvir RBV = ribavirin PEG = peginterferon SMV = simeprevir American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

28 Remember: What is the key step for treatment in HCV life cycle? Cleavage of polyprotein into functional and structural proteins The AIDS InfoNet. Available at: http://www.aidsinfonet.org/fact_sheets/view/670. Accessed: July 25, 2014

29 Processing the HCV Polyprotein Polyprotein precursor Viral core and envelope proteins Auto-protease: Cleaves NS2 – NS3 junction Acts as a protease and cleaves NS4B, NS5A and NS5B Serves as a helicase function during RNA replication Supports RNA replication Vital component of RNA replication complex and helps with new virus assembly Becomes HCV RNA polymerase Picture from: Rosen HR. New Engl J Med. 2011;364(25):2429-2438.

30 Pop Quiz: What is the MOA of sofosbuvir 1)Entry inhibitor 2)Integrase inhibitor 3)Protease inhibitor 4)Nucleoside analog polymerase inhibitor

31 Sofosbuvir: Mechanism of Action Sofosbuvir: Nucleoside analog polymerase inhibitor Prodrug that is converted to its active form (GS-461203) via intracellular metabolism Inhibits RNA-dependent RNA polymerase that is essential for viral replication Acts as a chain terminator Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2013. Available at: http://www.gilead.com/~/media/Files/pdfs/medicines/liver- disease/sovaldi/sovaldi_pi.pdf.

32 Neutrino Study ResponseSOF+RBV+peg-IFN for 12 weeks N = 327 HCV RNA <25 IU/mL – no./total no. (%) During treatment Week 2 Week 4 At last observed measurement After discontinuation of treatment Week 4 Week 12 299/327 (91) 321/325 (99) 326/327 (>99) 302/327 (92) 295/327 (90) Relapse – no./total no. (%) Patients who completed treatment Patients who did not complete treatment 25/320 (8) 3/6 (50) Lawitz E, et al. N Engl J Med. 2013;368(20):1878-1887.

33 Sofosbuvir Dose: 400 mg PO daily With or without food Administered with Peg & Ribavirin If drugs combined with sofosbuvir must be permanently discontinued, sofosbuvir should also be discontinued Drug interactions: Not metabolized by CYP enzymes, but P-gp substrate Not recommended to be used with: phenytoin, phenobarbital, carbamazepine, rifampin, and tipranavir/ritonavir Adverse effects: Most common include fatigue and headache Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2013. Available at: http://www.gilead.com/~/media/Files/pdfs/medicines/liver- disease/sovaldi/sovaldi_pi.pdf.

34 Simeprevir: Mechanism of Action Simeprevir: 2 nd generation protease inhibitor Inhibits NS3/4A protease, a protease that is essential for viral replication Considered a direct-acting antiviral treatment for HCV Also called a specifically targeted antiviral therapy for HCV (STAT-C) Olyseo TM [package insert]. Titusville, NJ: Janssen Products, LP; 2013. Available at: https://www.olysio.com/shared/product/olysio/prescribing-information.pdf

35 Quest-1 & Quest-2 SMV + PEG/ RBV PBO + PEG/ RBV Pooled analysis of simeprevir plus PegIFN/RBV for treatment of treatment-naïve patients with genotype 1 infection versus PBO/PR: SVR12 week Rockstroh JK. Summary from AASLD 3013 for Hepatitis C. Available at: http://www.natap.org/2013/AASLD/AASLD_109.htm. Accessed July 27, 2014.

36 Simeprevir Dosing: 150 mg PO daily With food Administered with Peg & Ribavirin If drugs combined with simeprevir must be permanently discontinued, simeprevir should also be discontinued Drug interactions: Metabolized by CYP 3A4 enzymes and an inhibitor of intestinal 3A4, but NOT hepatic 3A4 Not recommended to be used with: cobicistat, efavirenz, etravirine, and HIV protease inhibitors Q80K polymorphism: pretreatment testing on genotype 1a patients should be considered for simeprevir Adverse effects: Rash (including photosensitivity), pruritus, and nausea Olyseo TM [package insert]. Titusville, NJ: Janssen Products, LP; 2013. Available at: https://www.olysio.com/shared/product/olysio/prescribing-information.pdf

37 Ribavirin & Peginterferon Ribavirin Hemolytic anemia* Expect 3 g/dL decrease in Hgb in first 2 – 4 weeks Caution for CrCl < 50 mL/min Pregnancy category X Women of childbearing age and partners of men receiving ribavirin MUST use effective contraception during and 6 months after Peginterferon Flu-like symptoms Up to 100% of patients GI intolerance (20 – 65%) Anorexia, abdominal pain, nausea, and vomiting Neuropsychiatric toxicity (20- 50%) Irritability, depression, confusion, anxiety, insomniaNeutropenia*Thrombocytopenia* * Need to monitor WBCs & platelets (IFN) + RBCs & Hgb (RBV) Ribavirin and peginterferon. Lexi-drugs OnlineTM. Lexicomp. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://online.lexi.com.

38 HCV 2014 Guidelines: Treatment Dictated by: Monoinfection with genotype Treatment experience: nonresponders Co-infection with HIV Presence of Cirrhosis Post-Liver transplant Renal Impairment Concomitant medications American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

39 HCV Treatment: Genotype 1 & Treatment Naïve Recommended Regimens: Regardless of subtype IFN Eligible* Sofosbuvir 400 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily + PEG weekly x 12 weeks IFN Ineligible* Sofobuvir 400 mg PO daily + simeprevir 150 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 12 weeks Alternative Regimens IFN Eligible & HCV genotype 1b or 1a without Q80K polymorphism* Simeprevir 150 mg daily x 12 weeks + RBV (1000 mg [ 75 kg]) PO daily + PEG weekly x 24 weeks IFN Ineligible* Sofosbuvir 400 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 24 weeks * IFN ineligible (1 or more): intolerance to IFN, autoimmune hepatitis, hypersensitivity to PEG, decompensated liver disease, history of depression or clinical features of depression, a baseline neutrophil count < 1500/ μ L, baseline platelet count < 90,000/ μ L, baseline hemoglobin < 10 g/dL, or history of preexisting cardiac disease American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

40 HCV Treatment: Genotype 1 & Nonresponders Recommended Regimens: Regardless of subtype Regardless IFN Ineligibility & Without HCV PI Nonresponder Sofosbuvir 400 mg PO daily + simeprevir 150 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 12 weeks With HCV PI Nonresponder Sofosbuvir 400 mg PO daily x 12 weeks + RBV (1000 mg [ 75 kg]) PO daily + PEG weekly x 12 – 24 weeks Alternative Regimens: Regardless of subtype With or without an HCV PI Nonresponder & IFN Eligible Sofosbuvir 400 mg PO daily x 12 weeks + RBV (1000 mg [ 75 kg]) PO daily + PEG x 12 – 24 weeks OR Without and HCV PI Nonresponder & IFN Eligible Simeprevir 150 mg PO daily x 12 weeks + RBV (1000 mg [ 75 kg]) PO daily + PEG x 48 weeks IFN Ineligible* Sofosbuvir 400 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily for 24 weeks American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

41 HCV Treatment: Genotype 1 & HIV Co-infection Recommended Regimens: Regardless of subtype IFN Eligible: Treatment naïve AND prior relapser Sofosbuvir 400 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily + PEG weekly x 12 weeks IFN Ineligible: Treatment naïve Sofosbuvir 400 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 24 weeks OR IFN Ineligible: Prior relapser or (treatment naïve) Sofosbuvir 400 mg PO daily + simeprevir 150 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 12 weeks Treatment experienced: PEG/RBV nonresponse (regardless IFN) Sofosbuvir 400 mg PO daily + simeprevir 150 mg PO daily + RBV (1000 mg [ 75 kg]) PO daily x 12 weeks Treatment Experienced: PEG/RBV + Tel or Bos Nonresponse Treatment as recommended for HCV-monoinfected individuals American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

42 PHOTON-1 Trial On-treatment and sustained virologic response Sulkowski, et al. JAMA. 2014;312(4):353-361.

43 MJs Treatment What would be the best HCV treatment for MJs HCV monoinfection? What if MJ was diagnosed with HCV and HIV co-infection, what would be the best treatment option at this time?

44 Coming Soon…… When and in whom to initiate therapy: Target Launch – Summer 2104 Monitoring patients who are on or have completed therapy: Target Launch – Summer 2014 Management of acute HCV infection: Target Launch – Summer 2014 American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014.

45 In the Pipeline: Sofosbuvir/Ledipasvir – LONESTAR Trial S/L - RBV S/L + RBV SVR12 results for the different cohorts Rockstroh JK. Summary from AASLD 3013 for Hepatitis C. Available at: http://www.natap.org/2013/AASLD/AASLD_109.htm. Accessed July 27, 2014.

46 Conclusion Understand the guidelines have certain parameters that dictate treatment There are remarkable new treatments available and in the pipeline May eliminate need for PEG and even ribavirin in certain populations Treatment costs: “Challenges Highlighted For Firm Amid Surge In Sales Of Hepatitis Medicine. ” Sofosbuvir and simeprevir

47 References 1.Centers for Disease Control and Prevention. Available at: http://www.cdc.gov. Accessed July 25, 2014. 2.Centers for Disease Control and Prevention. Hepatitis C information for health professionals. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#statistics. Accessed July 25, 2014. 3.Branch AD, Van Natta ML, Vachon ML. Mortality in Hepatitis C Virus-infected patients with a diagnosis of AIDS in the era of combination antiretroviral therapy. CID. 2012;55:137-144. 4.The AIDS InfoNet. Available at: http://www.aidsinfonet.org/fact_sheets/view/670. Accessed: July 25, 2014. 5.American Association for the Study of Liver Diseases/Infectious Diseases Society of America, with International Antiviral Society–USA. Recommendations for testing, managing, and treating hepatitis C. Available at: http://www.hcvguidelines.org/full-report-view. Accessed July 24, 2014. 6.PubMed health. Hepatitis C. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001329/. Accessed July 25, 2014. 7.Center for Disease Analysis. Hepatitis C. Available at: http://www.centerforda.com/Maps/World%20P.jpg. Accessed July 26, 2014.

48 References Continued 8.Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(4):1433-1444. 9.Rosen HR. Chronic hepatitis C infection. New Engl J Med. 2011;364(25):2429- 2438. 10.Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2013. Available at: http://www.gilead.com/~/media/Files/pdfs/medicines/liver- disease/sovaldi/sovaldi_pi.pdf. Accessed July 25, 2014. 11.Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-1887. 12.Olyseo TM [package insert]. Titusville, NJ: Janssen Products, LP; 2013. Available at: https://www.olysio.com/shared/product/olysio/prescribing-information.pdf. Accessed July 27, 2014. 13.Rockstroh JK. Summary from AASLD 3013 for Hepatitis C. Available at: http://www.natap.org/2013/AASLD/AASLD_109.htm. Accessed July 27, 2014. 14.Ribavirin and peginterferon. Lexi-drugs OnlineTM. Lexicomp. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://online.lexi.com. Accessed July 26, 2014. 15.Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for Hepatitis C in patients with HIV coinfection. JAMA. 2014;312(4):353-361.

49 Questions?


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