Your Annual Hepatitis C Update

Transcription

1 Your Annual Hepatitis C Update Bernadette Jakeman, Pharm.D. Associate Professor University of New Mexico, College of Pharmacy Nimish Patel, Pharm.D., Ph.D. Associate Professor University of California San Diego, Skaggs School of Pharmacy & Pharmaceutical Sciences Annual Meeting & Exposition Seattle, Washington March 22 25

2 Disclosures Dr. Jakeman has nothing to disclose. Dr. Patel has received investigator initiated research support from Gilead Sciences and Merck. 2

3 CPE Information Target Audience: Pharmacists ACPE#: L01 P Activity Type: Knowledge based 3

4 Supporter This activity is supported by independent educational grants from Gilead Sciences Inc.a

5 Learning Objectives At the completion of this knowledge based activity, participants will be able to: 1. Identify important changes in recently updated guidelines that have the potential to influence the management of hepatitis C virus (HCV) infection. 2. Describe clinically important drug updates, adverse effects, and drug drug interactions associated with new drug classes used in the treatment of HCV infection. 3. Outline strategies for improving patient adherence to drug therapy for HCV infection and its comorbidities. 5

6 Assessment Questions 1. Which of the following ways is hepatitis C transmitted? A. Through raw/uncooked meat B. Through percutaneous/permucosal blood exposure C. Through person to person contact with saliva D. Through use of public toilet seats 6

7 Assessment Questions 2. Which of the following drugs should not be co administered with sofosbuvir? A. Acetaminophen B. Aspirin C. Amlodipine D. Amiodarone E. Atenolol 7

8 Assessment Questions 3. Which of the following medications requires resistance testing prior to use in patients with HCV genotype 1a infection? A. Sofosbuvir/ledipasvir B. Sofosbuvir/velpatasavir C. Glecaprevir/pibrentasvir D. Elbasvir/grazoprevir 8

9 Assessment Questions 4. Which of the following is NOT a factor that would affect adherence to HCV medications? A. Number of pills needed to ingest per dose B. Multiple times per day dosing frequency C. Concomitant administration with food D. Polypharmacy and drug interactions 9

10 Estimated 70 Million Persons Living With HCV Prevalence (Viremic) 0% to < 0.6% 0.6% to < 0.8% 0.8% to < 1.3% 1.3% to < 2.9% 2.9% to < 6.7% 10 Polaris Observatory HCV Collaborators. Lancet Gastroenterol Hepatol. 2017;2:

11 Epidemiology of HCV 1 3 Approximately 2 4 million people in the US are infected with HCV More common in males and black non Hispanics Majority of cases are in persons born between At least 50% of cases are unaware that they are infected Up to 85% of patients who become infected develop chronic infection Genotype 1 is the most common in US 1. Hofmeister MG, et al. Hepatology Nov doi: /hep [Epub ahead of print]. 2. Denniston MM, et al. Ann Intern Med 2014;160: Monina Kevens R, et al. CID 2012;55:S3. 11

12 Distribution of HCV Genotypes in United States 6% 1% 2% 3% 10% 27% 51% 1a 1b 2a 2b 3a 4 6 Nainan OV. Gasteroenterology. 2006; 131: *Prevalence of genotype 5 is <1% and not displayed in chart 12

13 Incidence of HCV in United States YEAR CDC. Viral hepatitis statistics and surveillance # of New HCV Infections

14 Risk Factors Persons living born between 1945 to 1965 Current or former injection drug use Patients receiving blood transfusions before 1992 Patients receiving clotting factors before 1987 (e.g., hemophiliacs) Sexual contact with HCV positive persons Children born to HCV positive mothers Occupational exposure Unprofessional tattoos or piercings Conditions associated with potential risk (e.g., chronic hemodialysis, transplant) 14

15 Chronic HCV Infection Lingala S et al. Gastroenterol Clin North Am 2015;44:717. HCC hepatocellular carcinoma ESLD end stage liver disease 15

16 Accelerated Progression of HCV in Patients Living with HIV % Cirrhosis Di Martino V, et al. Hepatology. 2001;34: HCV Infection Duration (years) 69 HCV HCV + HIV Abbreviations: HCV hepatitis C virus; HIV human immunodeficiency virus 16

17 Extrahepatic Manifestations 1 6 Depression Fatigue Cryoglobulinemia Diabetes Cardiovascular disease Arthralgias/myalgias Neuropathy Cancer 1 Adinolfi LE et al. Clin Liver Dis 2017;21: Foster GR et al. Hepatology 1998;27: Karaivazogluou K et al. Ann Hepatol 2010;9: Cacoub P. Ther Adv Infect Dis 2016;3:3. 5 Adinolfi L et al Atherosclerosis 2012:221: Mason A et al. Hepatology 1999;29:

18 HCV Disease and Progression Decompensated cirrhosis Hepatorenal syndrome Increased risk of hepatocellular carcinoma Need for hepatic transplantation Mortality All of these items are associated with considerable healthcare expenditures 18 AASLD/IDSA. HCV Guidance May 2018.

19 Assessing Extent of Liver Disease Helpful in determining urgency of HCV treatment Non invasive methods Liver directed physical exam (normal in most patients) Routine blood tests (eg, ALT, AST, albumin, bilirubin, international normalized ratio, and CBC with platelet count) Serum fibrosis marker panels FIB 4, AST:Platelet ratio index, Fibroscan/Fibrosure, etc Liver imaging (eg, ultrasound, or CT scan) Transient elastography Invasive methods Biopsy METAVIR fibrosis score AASLD/IDSA. HCV Guidance May Abbreviations: ALT alanine aminotransferase; AST aspartate aminotransferase, CBC complete blood count; CT computed tomography; METAVIR Metaanalysis of Histological Data in Viral Hepatitis 19

20 HCV screening A 50 years old female completed 8 weeks of HCV treatment with glecaprevir/pibrentasvir in October The patient s most recent HCV antibody screening test from February 2019 is positive. How would you interpret this test? A. Patient is reinfected with HCV B. Patient is cured of HCV C. Patient has been exposed to HCV D. Cannot be determined until 6 months post treatment completion; reorder antibody in April

21 CDC. Testing for HCV Infection: An update of guidance for clinicians and laboratorians. MMWR 2013:62(18). 21

22 Recommendations for HCV Screening Persons born between regardless of risk Risk behaviors Injection drug use (current or prior) Intranasal illicit drug use Risk exposures Persons on long term hemodialysis (ever) Percutaneous/parenteral exposures in an unregulated setting Occupational exposure to HCV infected blood Children born to HCV infected women Prior recipients of transfusions/organ transplants pre 1992 or clotting factor pre 1987 Persons who were ever incarcerated Other HIV Infection Sexually active pre exposure prophylaxis (PrEP) recipients Unexplained chronic liver disease and/or chronic hepatitis, including elevated ALT levels Solid organ donors (deceased and living) 22 AASLD/IDSA. HCV Guidance May 2018.

23 Pretreatment Considerations HCV genotype HCV viral load Presence of cirrhosis Prior treatment failure and resistance Renal function Hepatitis B co infection Drug interactions 23 AASLD/IDSA. HCV Guidance May 2018.

24 Goal of HCV Treatment Reduce all cause mortality Reduce liver related health adverse consequences End stage liver disease Hepatocellular carcinoma Achievement of virologic cure as evidenced by a sustained virologic response (SVR) SVR = Absence of HCV RNA 12 weeks after completion of therapy 24 AASLD/IDSA. HCV Guidance May 2018.

25 SVR Equivalent to Viral Cure Nearly 100% of patients who achieve SVR remain undetectable during long term follow up [1 4] [1] 99 [2] 100 [3] 100 [4] Patients With SVR (%) yrs (mean) 3.4 yrs (median) 3.3 yrs (median) 5.4 yrs (median) Duration of Follow up 1. Swain MG, et al. Gastroenterology. 2010;139: Giannini EG, et al. Aliment Pharmacol Ther. 2010;31: Maylin S, et al. Gastroenterology. 2008;135: George SL, et al. Hepatology. 2009;49:

26 Treatment Landscape over Time Frequent curability of diverse populations without IFN Simeprevir + Sofosbuvir (GT1) Telaprevir and Boceprevir (GT1) Daclatasvir + Asunaprevir (Japan) Daclatasvir + Sofosbuvir (Europe) Ombitasvir/ Paritaprevir/RTV (GT4) + Dasabuvir (GT1) Daclatasvir + Sofosbuvir (GT3) (2016: GT1) Sofosbuvir/Velpatasvir/ Voxilaprevir (DAA failures, all genotypes) Sofosbuvir/ Velpatasvir (all genotypes)? Interferon Era Curability of HCV without IFN Simeprevir or Sofosbuvir with IFN (GT1) First approved IFN-free therapy: Sofosbuvir + RBV (GT2,3) Grazoprevir/ Elbasvir (GT1,4) Glecaprevir/ Pibrentasvir (all genotypes) References in slide notes; Abbreviations: DAA direct acting antiviral; GT1 genotype 1; GT1,4 genotype 1 and 4; GT2,3 genotype 2 and 3; GT3 genotype 3; GT4 genotype 4; HCV hepatitis C virus; IFN interferon; 26

27 Abbreviations Older HCV treatments: BOC boceprevir& TPV telaprevir IFN interferon & Peg IFN pegylated interferon PrOD paritaprevir/ritonavir/ombitasvir/dasabuvir RBV ribavirin SIM simeprevir Contemporary HCV treatments DCV daclatasvir EBV elbasvir GLE glecaprevir GZP/GRZ grazoprevir LDV ledipasvir PIB pibrentasvir SOF sofosbuvir VEL velpatasvir VOX voxilaprevir 27

28 HCV Cure Rates by Coinfection Status SVR12 (%) Monoinfection IFN IFN + RBV Peg IFN + RBV HCV/HIV Coinfection PR + BOC/TPV PR + SOF/SIM SOF/LED PrOD DCV + SOF ELB/GRZ SOF/VEL GLE/PIB AASLD/IDSA. HCV Guidance May 2018.

29 Direct Acting Antivirals (DAAs) NS3/4A Inhibitors (Protease Inhibitors) previr Grazoprevir Glecaprevir Voxilaprevir NS5A Inhibitors (Replication Complex Inhibitors) asvir Ledipasvir Daclatasvir Elbasvir Velpatasvir Pibrentasvir NS5B (Polymerase Inhibitors) buvir Sofosbuvir 29 AASLD/IDSA. HCV Guidance May 2018.

30 HCV Treatment guidelines Collaborative guidelines published by: American Association for the Study of Liver Diseases (AASLD) Infectious Diseases Society of America (IDSA) International Antiviral Society USA (IAS USA) Guidelines are web based given the rapid development of new agents in HCV pharmacotherapy 30 AASLD/IDSA. HCV Guidance May 2018.

31 AASLD Treatment Guidelines GT1 Treatment Experience Treatment naive PegIFN/RBV experienced NS3 protease inhibitor + PegIFN experienced Recommended Regimens for GT1 EBR/GZR* 12 wks GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis LDV/SOF 12 wks LDV/SOF 8 wks if no cirrhosis, non-black, no HIV, HCV RNA < 6 million IU/mL SOF/VEL 12 wks EBR/GZR* 12 wks GLE/PIB 8 wks (only if no cirrhosis) LDV/SOF 12 wks (only if no cirrhosis) SOF/VEL 12 wks GLE/PIB 12 wks (compensated cirrhosis) LDV/SOF 12 wks (only if no cirrhosis) SOF/VEL 12 wks GLE/PIB 12 wks *For GT1a, only if no baseline NS5A elbasvir RASs detected; otherwise 16 weeks. 31 AASLD/IDSA. HCV Guidance May 2018.

32 AASLD Treatment Guidelines GT2 Treatment Experience Treatment naive Recommended Regimens for GT3 GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis SOF/VEL 12 wks PegIFN/RBV experienced SOF/RBV experienced GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis SOF/VEL 12 wks GLE/PIB 12 wks SOF/VEL 12 wks SOF + NS5A inhibitor experienced SOF/VEL/VOX 12 wks 32 AASLD/IDSA. HCV Guidance May 2018.

33 AASLD Treatment Guidelines GT3 Treatment Experience Treatment naive Recommended Regimens for GT2 GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis SOF/VEL 12 wks PegIFN/RBV experienced SOF/VEL 12 wks EBR/GZR + SOF 12 wks (if compensated cirrhosis) SOF/VEL/VOX 12 wks (if compensated cirrhosis) SOF/VEL/VOX +/- RBV 12 wks DAA experienced 33 AASLD/IDSA. HCV Guidance May 2018.

34 AASLD Treatment Guidelines GT4 Treatment Experience Treatment naive PegIFN/RBV experienced DAA-experienced Recommended Regimens for GT4 GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis SOF/VEL 12 wks EBR/GZR 12 wks LDV/SOF 12 wks GLE/PIB 8 wks if no cirrhosis, 12 wks if compensated cirrhosis SOF/VEL 12 wks EBR/GZR 12 wks LDV/SOF 12 wks (non-cirrhotic only) SOF/VEL/VOX 12 wks 34 AASLD/IDSA. HCV Guidance May 2018.

35 Glecaprevir/Pibrentasvir Pan genotypic (GT 1 6) 8 week regimen if non cirrhotic for ALL genotypes Otherwise 12 weeks if cirrhotic or previous treatment with DAAs Sig: 3 tablets daily with food Huge opportunity for pharmacists to prevent medication errors No renal dose adjustment necessary Recommended for patients with stage 4/5 chronic kidney disease Cannot be used in decompensated cirrhosis Metabolized by CYP3A Watch for drug drug interactions 35 FDA. Mavyret AASLD/IDSA. HCV Guidance May 2018.

36 Ledipasvir/Sofosbuvir Genotypes 1, 4 6 Demonstrated efficacy in several difficult to treat populations Data in patients with decompensated cirrhosis Data in adolescents and emerging pediatric data Convenience: single tablet regimen; duration varies 8 24 weeks 8 wks: GT1, treatment naïve, non cirrhotic, no HIV, non black and HCV RNA <6 million Sig: 1 tablet daily with or without food Not evaluated in patients with creatinine clearance < 30 ml/min Drug interactions with other P glycoprotein inhibitors DO NOT USE SOFOSBUVIR WITH AMIODARONE FDA. Harvoni. 2014; AASLD/IDSA. HCV Guidance May

37 Sofosbuvir/Velpatasvir Pan genotypic (GT 1 6) Demonstrated efficacy in several difficult to treat populations Data in patients with decompensated cirrhosis Convenience: single tablet regimen; duration varies weeks Sig: 1 tablet daily with or without food Velpatasvir requires an acidic environment for absorption Not evaluated in patients with CrCL < 30 ml/min Can be used safely with several antiretrovirals 37 FDA. Epclusa. 2016; AASLD/IDSA. HCV Guidance May 2018.

38 Sofosbuvir/ Velpatasvir/ Voxilaprevir Pan genotypic (GT 1 6) Demonstrated efficacy in several difficult to treat populations Data in patients with previous treatment with DAA Convenience: single tablet regimen; 12 weeks Sig: 1 tablet daily with or without food Requires an acidic environment for absorption Do not exceed 20mg omeprazole or famotidine 40mg BID Not evaluated in patients with CrCL < 30 ml/min Interactions with some (not all) statins 38 FDA. Vosevi. 2017; AASLD/IDSA. HCV Guidance May 2018.

39 Elbasvir/Grazoprevir Approved for genotypes 1a, 1b and 4 For GT 1a, need to perform NS5A test for polymorphisms at position 28, 30, 31, 93; extends therapy to 16 weeks NOT for use in decompensated cirrhosis Convenience: single tablet regimen; duration varies weeks Sig: 1 tablet daily with or without food No renal dose adjustment necessary Recommended for patients with stage 4/5 chronic kidney disease Limited number of antiretrovirals that can be used concomitantly 39 FDA. Zepatier. 2016; AASLD/IDSA. HCV Guidance May 2018.

40 Ribavirin (Non DAA) Used in combination with DAAs Recommended in difficult to treat cases (e.g., cirrhosis, resistance) Weight based dosing Titrated based on tolerance Administered twice daily (nausea) Risk of hemolytic anemia Known teratogen 2 forms of contraception needed Contraception needed during treatment and up to 6 months after 40 AASLD/IDSA. HCV Guidance May 2018.

41 Common Side Effects of DAAs Regimen Headache Fatigue Nausea Diarrhea Glecaprevir/Pibrentasvir X X Ledipasvir/Sofosbuvir X X Elbasvir/Grazoprevir X X Sofosbuvir/Velpatasvir X X Sofosbuvir/Velpatasvir/ Voxilaprevir X X X 41 FDA. Harvoni. 2014; AASLD/IDSA. HCV Guidance May 2018.

42 Lab Monitoring Prior to treatment initiation: CBC, INR, hepatic function panel, creatinine level, calculated GFR, HCV genotype and subtype, hepatitis B antigen, hepatitis B surface antibody, hepatitis B core antibody After 4 weeks of treatment and as clinically indicated: CBC, creatinine level, calculated GFR, and hepatic function panel May do more frequently if indicated Quantitative HCV viral load: Prior to initiation At week 4 (strong predictor of treatment response) At end of therapy (optional) 12 weeks AFTER the END of therapy (determine if SVR is achieved) Hepatocellular carcinoma (HCC) surveillance after treatment completion: Patients with advanced fibrosis (>F3) Abdominal ultrasound every 6 months AASLD/IDSA. HCV Guidance May Abbreviations: CBC complete blood count; GFR glomerular filtration rate; HCV hepatitis C virus; INR international normalized ratio; SVR 42 sustained virologic response

43 Drug Drug Interactions Concomitant Medication SOF/LDV EBR/GZR GLE/PIB SOF/VEL SOF/VEL/VOX Acid-reducing agents* Amiodarone X* X* X* X X X Anticonvulsants* X X X X X Azole antifungals* Calcineurin inhibitors,* cisapride, PDE inhibitors,* other antiarrhythmics* or sedatives* Calcium channel blockers* X X X Cyclosporine X X X indicates interaction, but not necessarily contraindicated. SOF = sofosbuvir; LDV = ledipasvir; EBR = elbasvir; GZR = grazoprevir; GLE = glecaprevir; PIB = pibrentasvir; VEL = velpatasvir; VOX = voxilaprevir. *Some DDIs not class specific; see prescribing information for specific drugs within a class. Requires DCV dose adjustment. AASLD/IDSA. HCV guidance. May FDA GLE/PIB. 43

44 Drug Drug Interactions Concomitant Medication SOF/LDV EBR/GZR GLE/PIB SOF/VEL SOF/VEL/VOX Digoxin X X X X X Ethinyl estradiol containing products X Glucocorticoids* X Herbals, St John s wort, milk thistle X X X X X Statins* X X X X X Macrolide antimicrobials* X Rifamycin antimicrobials* X X X X X X indicates interaction, but not necessarily contraindicated. SOF = sofosbuvir; LDV = ledipasvir; EBR = elbasvir; GZR = grazoprevir; GLE = glecaprevir; PIB = pibrentasvir; VEL = velpatasvir; VOX = voxilaprevir. *Some DDIs not class specific; see prescribing information for specific drugs within a class. Requires DCV dose adjustment. AASLD/IDSA. HCV guidance. May FDA GLE/PIB. 44

45 druginteractions.org 45

46 Drug Drug Interactions Sofosbuvir increases effect of amiodarone Avoid concomitant use Includes current or recent prior use of amiodarone May result in serious symptomatic bradycardia and heart block Glecaprevir/pibrentasvir and ethinyl estradiol Risk of ALT elevations Coadministration of ethinyl estradiol containing hormonal contraceptives or hormone replacement therapies is not recommended Fontaine H. N Engl J Med 2015; 373: ; druginteractions.org 46

47 Drug Drug Interactions Acid suppressants and NS5A inhibitors Decreased absorption of velpatasvir > ledipasvir Requires acidic environment for absorption Avoid if possible Do not use: Omeprazole doses >20mg daily Famotidine doses >40mg daily No issue with pibrentasvir or elbasvir druginteractions.org 47

48 Drug Drug Interactions Most DAAs have potential to interact with statins (i.e., atorvastatin, lovastatin, rosuvastatin, simvastatin) Increases statin concentrations increases risk for toxicity Includes: glecaprevir/pibrentasvir, elbasvir/grazoprevir, ledipasvir, velpatasvir If no history of cardiovascular event may consider holding statin therapy druginteractions.org 48

49 Drug Drug Interactions with Antiretrovirals HIV Antiretroviral Agent SOF/LDV EBR/GZR GLE/PIB SOF/VEL SOF/VEL/VOX Abacavir/lamivudine Tenofovir alafenamide (TAF)/emtricitabine Tenofovir disoproxil fumerate TDF* TDF* TDF* (TDF)/emtricitabine Dolutegravir Bictegravir Raltegravir Elvitegravir/cobicistat** LDV GZR HIV protease inhibitor with ritonavir GZR GLE PIB PI (ATV) Efavirenz** EBR GZR GLE PIB VEL VEL SOF = sofosbuvir; LDV = ledipasvir; EBR = elbasvir; GZR = grazoprevir; GLE = glecaprevir; PIB = pibrentasvir; VEL = velpatasvir; VOX = voxilaprevir; PKE = pharmacokinetic enhance (i.e., ritonavir or cobicistat). *Not recommended especially if given with PKE; **Review drug interactions if co formulated with TDF druginteractions.org 49

50 Special Populations Populations who may require additional considerations and consultation with a specialist when selecting/monitoring HCV treatment: HIV/HCV coinfection Decompensated cirrhosis Post liver transplant Renal impairment Kidney transplant Acute infection Pregnancy Children People who inject drugs (active) Men who have sex with men Corrections 50

51 Adherence Factors that may hinder adherence Food requirements (GLE/PIB) Multiple tablets per dose (GLE/PIB) Consequences of poor adherence Treatment failure Resistance development 51

52 Pharmacists Role in HCV Management Assist in selection of HCV regimen Cost considerations Prior authorization process and patient assistance programs Review risk for potential drug drug interactions Assess for side effects Check for drug drug interactions at each visit New medications Over the counter medications Promote adherence Pill boxes Alarms Other aids Assist with appropriate follow up 52

53 Vignette 1 57 year old Caucasian male Veteran History of injection drug use since returning from Desert Storm PMH significant for compensated cirrhosis, HIV, dyslipidemia, and diabetes Controlled with tenofovir DF/emtricitabine/cobicistat/elvitegravir, atorvastatin and metformin Fully adherent to medications HIV viral load is consistently undetectable and CD4 count ~ cells/mm 3 Was infected with HCV genotype 1 Treated with ledipasvir/sofosbuvir x 12 weeks and cured Patient returns to hepatology clinic after several months of missed appointments in HIV clinic and admitting to going on a bender Most recent labs reveal: HCV Ab (+), HCV RNA (365,000 copies/ml), Genotype 3 53

54 Vignette 1 Would you re treat this patient? A) No, too expensive B) No, the drugs don t work in patients who are re infected C) No, IV drug use demonstrates inability to be adherent to meds D) Yes, DAA and substance abuse rehab simultaneously 54

55 Vignette 1 AASLD/IDSA. HCV Guidance May

56 High SVR Rates in People who Inject Drugs 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 94% 3% 2% 1% SVR Achieved SVR Not Achieved Lost to Follow Up Died d/t Overdose Grebely J et al. SIMPLIFY Study Group. Lancet Gastroenterol Hepatol 2018;3:

57 Vignette 1 Given that he had previously received ledipasvir/sofosbuvir for genotype 1 HCV infection, what would you treat his current genotype 3 HCV infection with? A) Glecaprevir/pibrentasvir x 12 weeks B) Ledipasvir/sofosbuvir x 12 weeks C) Velpatasvir/voxilaprevir/sofosbuvir x 12 weeks D) Velpatasvir/sofosbuvir x 12 weeks 57

58 Vignette 1 Summary This patient received glecaprevir/pibrentasvir x 12 weeks after changing HIV medications to bictegravir/tenofovir alafenamide/emtricitabine and stopping atorvastatin Pt was experiencing extreme insomnia and stopped taking medications for a week without telling anyone When he was called at week 4 to remind him of labs and when his refill would be ready, he said he had ~60 pills left Pt was only taking 1 tablet instead of 3 tablets per day. HCV RNA at week 4 was 550 copies/ml (down from 365,000 copies/ml before treatment) Began taking medication correctly and patient achieved SVR 58

59 Vignette 2 A 46 year old Hispanic male Risk factor: men who have sex with men (MSM), new partner in October 2018 PMH: HIV (previously well controlled with undetectable viral load, CD4 630 cells/mm 3 ), gastroesophageal reflux disease, acute HCV infection with genotype 3 (PCR positive November 2018) Referred to pharmacy clinic for detectable viral load of 71copies/mL (blip) No history of cirrhosis or injection drug use Prior labs in July 2018: HCV antibody nonreactive, hepatitis B antigen nonreactive, hepatitis B surface antibody titer >1000 (reactive), hepatitis B core antibody nonreactive Medications Darunavir/cobicistat/emtricitabine/tenofovir alafenamide 1 tablet daily Omeprazole 20mg 1 capsule daily 59

60 Vignette 2 Laboratory July 2018 Nov 2018 Dec 2018 Jan 2019 Feb 2019 HCV PCR (copies/ml) 9,460,000 11,100,000 Alb (g/dl) AST (IU/mL) ALT (IU/mL) T bili (mg/dl) Platelets (10 9 per L) INR SCr (mg/dl) HIV PCR (copies/ml) undetectable 71 undetectable CD4 cell count (cells/mm 3 )

61 Vignette 2 Should this patient be treated? 61

62 Vignette 2 AASLD/IDSA. HCV Guidance May

63 Vignette 2 Which of the following would be the best treatment option in this patient based on his current HIV antiretroviral regimen? a) Glecapravir/pibrentasvir x 8 weeks b) Sofosbuvir/velpatasvir x 12 weeks c) Sofosbuvir/ledipasvir x 8 weeks d) sofosbuvir plus ribavirin x 12 weeks 63

64 Vignette 2 What are your recommendations regarding omeprazole use while on HCV treatment? a) Stop omeprazole b) Continue with omeprazole 20mg c) Increase omeprazole dose to 40mg d) Switch to pantoprazole 40mg 64

65 Vignette 3 66 year old male with genotype 1a HCV infection Patient was treatment naïve and has cirrhosis (Child Pugh class A) Patient was infected in his 20 s via shared needles HCV RNA was 24 million prior to treatment Patient had consistently elevated serum creatinine ( mg/dL) and egfr is usually 5 20 ml/min Patient had resistance testing performed and had no polymorphisms Patient was taking atorvastatin 20mg/day, lisinopril 5mg/day and aspirin 81mg/day 65

66 Vignette 3 Which HCV medication would you use to treat this patient? A) Ledipasvir/sofosbuvir x 12 weeks B) Elbasvir/grazoprevir x 12 weeks C) Velpatasvir/sofosbuvir/voxilaprevir x 12 weeks D) Velpatasvir/sofosbuvir x 12 weeks 66

67 Vignette 3 Decision was made to discontinue atorvastatin and start therapy with elbasvir/grazoprevir Labs during the course of therapy are charted below Baseline HCV RNA: 24,000,000 Tx Week 4 HCV RNA: 2,000 Tx Week 8 HCV RNA: 56 Tx Week 12 HCV RNA: <12 67

68 Vignette 3 Has this patient achieved a sustained virologicresponse? A) Yes, the viral load is <12 B) No, <12 is still detectable C) No, labs need to drawn 12 weeks after ending therapy D) No, test is invalid in patients with abnormal renal function 68

69 Vignette 3 Decision was made to discontinue atorvastatin and start therapy with elbasvir/grazoprevir. Labs during the course of therapy are charted below Baseline HCV RNA: 24,000,000 Tx Week 4 HCV RNA: 2,000 Tx Week 8 HCV RNA: 56 Tx Week 12 HCV RNA: <12 12 weeks post tx HCV RNA: Below Detectable Limits 69

70 Vignette 4 34yo Caucasian female referred for HCV treatment initiation Diagnosed with HCV 2012, risk was prior injection use No significant past medical history Current HCV PCR 5,400,000 copies/ml, genotype 1a Patient non cirrhotic, treatment naïve, no prior hep B exposure (vaccinated 2008, hep B surface antibody reactive) SCr 0.6 mg/dl 70

71 Vignette 4 Which of the following is NOT recommended for HCV treatment in this patient case? a) Elbasvir/grazoprevir x 12 weeks b) Glecaprevir/pibrentasvir x 8 weeks c) Ledipasvir/sofosbuvir x 8 weeks d) Velpatasvir/sofosbuvir x 12 weeks e) Velpatasvir/sofosbuvir/voxilaprevir x 12 weeks 71

72 Vignette 4 Patient is prescribed Velpatasvir/sofosbuvir x 12 weeks based on insurance formulary She returns to clinic 2 weeks later and complains that she has not obtained the medication because she cannot afford the copay of $120 Patient also does not understand why the specialty pharmacy has been trying to contact her What options are available to this patient? 72

73 Patient Assistance Programs 73

74 Pharmacist Resources Hcvguidelines.org Live document and changes frequently University of Washington Hepatitis C website Training modules (CE credit available), calculators, charts, fact sheets University of Liverpool Hepatitis Interaction Checker Hep druginteractions.org Only captures drug interactions with hepatitis meds, will still need to check interactions within home medication list using another program AIDS Education and Training Center and hcv drug interactions quick guidesclinicians 74

75 Closing remarks/conclusion Landscape of HCV treatment has changed dramatically in the last decade Several well tolerated and highly effective orally administered treatment regimens available Treatment as short as 8 weeks in some situations Huge opportunity for pharmacists to impact care Adherence, drug interactions, treatment selection, etc Several patient resources available to make treatment affordable and accessible for most patients 75

76 Assessment Questions 1. Which of the following ways is hepatitis C transmitted? A. Through raw/uncooked meat B. Through percutaneous/permucosal blood exposure C. Through person to person contact with saliva D. Through use of public toilet seats 76

77 Assessment Questions 2. Which of the following drugs should not be co administered with sofosbuvir? A. Acetaminophen B. Aspirin C. Amlodipine D. Amiodarone E. Atenolol 77

78 Assessment Questions 3. Which of the following medications requires resistance testing prior to use in patients with HCV genotype 1a infection? A. Sofosbuvir/ledipasvir B. Sofosbuvir/velpatasavir C. Glecaprevir/pibrentasvir D. Elbasvir/grazoprevir 78

79 Assessment Questions 4. Which of the following is NOT a factor that would affect adherence to HCV medications? A. Number of pills needed to ingest per dose B. Multiple times per day dosing frequency C. Concomitant administration with food D. Polypharmacy and drug interactions 79

80 Questions Annual Meeting & Exposition Seattle, Washington March