1/16/2019. Goals of HCV Therapy. Objectives. Treating Hepatitis C and HIV Co Infection. Cure Defined as sustained virologic response (SVR)

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1 HCV ECHO WESTERN STATES HCV ECHO WESTERN STATES Treating Hepatitis C and HIV Co Infection Paulina Deming, Pharm D Associate Professor, College of Pharmacy Assistant Director, Viral Hepatitis Programs, Project ECHO University of New Mexico Health Sciences Center Conflict of Interest Disclosure Statement No conflicts Original presentation by: Date prepared: Objectives 1. Describe the expected course of treatment for HCV therapy using direct acting antivirals (DAAs) in a patient with HIV 2. Recognize the potential drug interactions with the DAAs, common medications, and HIV antiretrovirals 3. Describe the updated guidelines for HCV testing and treatment in men who have sex with men and in pregnancy Goals of HCV Therapy Cure Defined as sustained virologic response (SVR) Improvements in liver function Improvements in fibrosis, reversal of cirrhosis? Prevent decompensation Improvements in extrahepatic manifestations of HCV Prevent deaths due to liver disease complications Prevent liver cancer Reduce rates of liver cancer recurrence 1

2 The Evolution of Highly Effective Treatment HCV Direct Acting Antivirals (DAAs) 100 RBV 80 Standard IFN PegIFN BOC and TPV SOF SMV LDV/ SOF PrOD >90 > DCV+ SOF >90 EBR/ GZR >90 SOF/ VEL > SOF/ VEL/ GLE/ VOX PIB >90 >90 Target Pulled from market NS3/4A: Protease Inhibitors ( previr) Boceprevir Telaprevir Simeprevir Paritaprevir Grazoprevir Glecaprevir Voxilaprevir NS5A: Replication Complex Inhibitors ( asvir) Ledipasvir Ombitasvir Daclatasvir Elbasvir Velpatasvir Pibrentasvir NS5B: Polymerase Inhibitors ( buvir) Nucleotide: Sofosbuvir Non nucleoside: Dasabuvir 0 IFN 6 mos IFN mos IFN/ RBV 6 mos IFN/ RBV mos PegIFN RBV mos PegIFN/ RBV/ BOC or TPV 6- mos PegIFN/ PegIFN/ LDV/ RBV/ RBV/ SOF SMV SOF PrOD + RBV -24 SOF + DCV EBR/ GZR -16 SOF/ VEL SOF/ VEL/ VOX GLE/ PIB 8- HCV Direct Acting Antivirals (DAAs) Generic Name Elbasvir/ Grazoprevir Glecaprevir/Pibrentasvir Ledipasvir/Sofosbuvir Sofosbuvir/ Velpatasvir Sofosbuvir/ Velpatasvir/Voxilaprevir Paritaprevir/ritonavir/Ombitasvir Paritaprevir/ritonavir/Ombitasvir with Dasabuvir Single Agent Therapies Daclatasvir Sofosbuvir Brand Name Zepatier Mavyret Harvoni Epclusa Vosevi Technivie Viekira Pak, Viekira Pak XR Daklinza Sovaldi Case 1 56 yo female diagnosed with HIV and HCV in She is well controlled on her HAART. She was first approved for interferon based therapy in 2015 but did not follow up. In 2017, she was diagnosed with cirrhosis evaluated for HCV treatment several times. She was approved for therapy in 2017 and again in 2018 but has not started. Technivie and Viekira Pak XR to cease production January

3 Differences in Therapy Rapid Viral Decline Interferon Based Injectable Long duration of treatment High side effect profile Multiple laboratory abnormalities Low cure rates Direct Acting Antivirals Oral Short durations Minimal side effects Headache, fatigue Minimal laboratory abnormalities High cure rates Rapid Improvements in Inflammation Use of DAAs in Renal and Hepatic Impairment Elbasvir/grazo previr Ledipasvir/ sofosbuvir Sofosbuvir/ velpatasvir Glecaprevir/ pibrentasvir Sofosbuvir/ velpatasvir/ voxilaprevir HCV Genotype Efficacy Use in Cirrhosis Use in Renal Insufficiency 1*, 4 Childs class A Safe to use in all levels including hemodialysis 1, 4 Childs class A, B, C 1,2,3,4,5,6 Childs class A, B, C Limited to > 30 ml/min Limited to > 30 ml/min 1,2,3,4,5,6 Childs class A Safe to use in all levels including hemodialysis 1,2,3,4,5,6 Childs class A Limited to > 30 ml/min *Patients with HCV GT1a require pretreatment resistance testing 3

4 24 yo male recently diagnosed with HIV and HCV Case Questions WBC 4 Platelets 225 AST 253 ALT 361 Alb 4.3 Total bilirubin 0.5 INR 1 Creatinine 0.56 HepA total Abreactive HBsAb reactive HBcAb non reactive HbsAg non reactive HCV = 400,000 IU/mL Genotype 3 HIV 29,000 CD4 69 APRI 2.81 Should HIV or HCV be treated first? What drug drug interactions should be expected and avoided? Natural history following initial infection with HCV Time years years What Drug Drug Interactions Should be Expected and Avoided? Overall few clinically significant drug drug interactions expected with recommended HCV DAAs None expected with tenofovir alafenamide (TAF), emtricitabine, bictegravir, raltegravir, dolutegravir, or rilpivirine and ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir Few or no symptoms; can progress without signs for decades [1] Most pts asymptomatic until serious liver complications arise [2] 1. CDC. MMWR Morb Mortal Wkly Rep. 1998;47(RR 19): Heidelbaugh JJ, et al. Am Fam Physician. 2006;74:

5 Major Drug Drug Interactions for all Direct Acting Antivirals Carbamazepine Oxcarbazepine Phenytoin Phenobarbital Rifampin Expected to concentrations DO NOT USE WITH HCV THERAPY! Other Main Drug Interaction Concerns for DAAs Statins: Interactions vary by DAA and statin Acid suppressive therapy: Ledipasvir and velpatasvir require acidity for absorption greatest concern with velpatasvir Avoid amiodarone Amiodarone with sofosbuvir and other DAA: Serious symptomatic bradycardia Ethinyl estradiol Avoid with glecaprevir/pibrentasvir due to concerns for ALT elevations Avoid herbals St. Johns wort reduces efficacy University of Liverpool s Drug Interaction Checker Case Continued: Impact of underlying liver disease on HCV treatment 24 yo male recently diagnosed with HIV and HCV WBC 4 Platelets 225 AST 253 Markers of ALT 361 inflammation Alb 4.3 Markers of Total bilirubin 0.5 synthetic INR 1 function Creatinine 0.56 Hep A total Ab reactive HBsAb reactive HBcAb non reactive HbsAg non reactive HCV = 400,000 IU/mL Genotype 3 HIV 29,000 CD4 69 APRI

6 Natural history following initial infection with HCV 41 yo male with history of well controlled HIV and recent HCV infection Time years years Few or no symptoms; can progress without signs for decades [1] Most pts asymptomatic until serious liver complications arise [2] 1. CDC. MMWR Morb Mortal Wkly Rep. 1998;47(RR 19): Heidelbaugh JJ, et al. Am Fam Physician. 2006;74: week DAA regimens may be an option week DAA regimens are needed Meds: dolutegravir, emtricitabine tenofovir Labs: Albumin 4.1 g/dl, AST 93 U/L, ALT 245, total bili 0.8 mg/dl HCV GT1a, RNA 900,000 HIV Not detected Which of the following is best for treatment of his HCV? A. Elbasvir/grazoprevir x B. Glecaprevir/pibrentasvir x 8 C. Glecaprevir/pibrentasvir x D. Ledipasvir/sofosbuvir x 8 E. Either B or D Recommendations for HCV Treatment in Patients Living with HIV Treatment for Treatment Naïve Patients with Genotype 1a a If NS5A RAS testing is negative 6

7 41 yo male with history of well controlled HIV and recent HCV infection 28 yo male with HIV diagnosed in 2015 Meds: dolutegravir, emtricitabine tenofovir Labs: Albumin 4.1 g/dl, AST 93 U/L, ALT 245, total bili 0.8 mg/dl HCV GT1a, RNA 900,000 HIV Not detected Which of the following is best for treatment of his HCV? A. Elbasvir/grazoprevir x B. Glecaprevir/pibrentasvir x 8 C. Glecaprevir/pibrentasvir x D. Ledipasvir/sofosbuvir x 8 E. Either B or D Risk Factor IDU/MSM, on going IDU 3 4x per month HIV RNA < 20 IU/ml CD4 =584 cells/ul (41%) Other PMH: HCV, newly diagnosed 11/2016 (HCV Ab negative 9/2016) Major depression, PTSD Polysubstance abuse HAV immune (total antibody reactive) HBV (HBcAb reactive, HBsAg negative, HBsAb negative) Clinical Questions Should this patient be treated for HCV? Trends in AST and ALT with Corresponding HCV RNA Case 1 HCV RNA 2,000,000 How frequently should people who inject drugs be screened for HCV? AST ALT HCV RNA 675,000 HCV RNA 18,

8 New Recommendations: People Who Inject Drugs 25 yo male with chronic hepatitis C HCV/HIV Dx: 2017 Risk: IDU, MSM Allergies: NKDA Medications Albuterol Dolutegravir Emtricitabine Tenofovir alafenamide Prazosin Clinical Exam: Unremarkable HCV Treatment, 2017 Patient Re Engages in Care 5 later HCV Received 8 ledipasvir/sofosbuvir for genotype 1a infection (planned week course of therapy) 4 week HCV RNA not detected Lost to follow up at 8 of treatment HCV treatment stopped early (week 8) Which of the following is best? A. Finish 4 week course of medications B. Restart HCV therapy now C. Get HCV RNA now, if positive restart HCV therapy D. Get HCV RNA and genotype now 8

9 Case Continued How Best to Retreat? WBC 5.6 H/H 16.6/50 Platelet 222,000 Creatinine 0.93 TP 7.9 Alb 4.6 AST 46 ALT 104 TB 0.3 INR 1.0 HCV Genotype 2 HCV RNA: 504,000 HIV not detected FIB4: 0.51 APRI 0.52 A. Ledipasvir/sofosbuvir x B. Sofosbuvir/velpatasvir x C. Glecaprevir/pibrentasvir x 8 D. Sofosbuvir/velpatasvir/voxilaprevir x E. B or C 21 yo male presents to PrEP clinic. He is HIV negative. Does he need HCV testing? Other Recommendations for MSM 9

10 Universal Screening in Pregnancy What About Post Partum Management? Estimated 29,000 HCV positive women give birth annually Increase in HCV among young adults, including women of childbearing age Ly KN et al. Ann Intern Med. 2017;166: Watts T et al. MMWR. 2017;66: HCV in Children HCV ECHO WESTERN STATES End of Presentation Questions? 10