GUIDELINES FOR INCORPORATING HIV/HCV PREVENTION INTO MEDICAL CARE

Transcription

1 GUIDELINES FOR INCORPORATING HIV/HCV PREVENTION INTO MEDICAL CARE JOHN I. MCNEIL, MD, FACP MAXIMED ASSOCIATES MARYLAND JANUARY 25, 2018

2 CME Disclosures: Planning Committee And Speaker Speaker: The following speaker has nothing to disclose in relation to this activity: John I. McNeil, MD

3 Howard University CME Accreditation Sponsor Accreditation: Howard University College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credits for Physicians: Howard University College of Medicine, Office of Continuing Medical Education, designates this live activity for a maximum of 1.0 AMA PRA Category I Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Goulda A. Downer, PHD, RD, LN, CNS Principal Investigator/Project Director

4 CME Disclosures: Planning Committee And Speaker AETC-Capitol Region Telehealth Project Planning Committee: The following committee members have nothing to disclose in relation to this activity: Goulda A. Downer, PhD, RD, LN, CNS John I. McNeil, MD John Richards, MA-AITP Denise Bailey, MED Speaker: The following speaker has nothing to disclose in relation to this activity: John I. McNeil, MD

5 Howard University CME Accreditation Requirements For Internet Viewers Intended Audience: Health service providers: Physicians, Physician Assistants, Nurse Practitioners, Pharmacists, Dentists, Nurses, Social Workers, Case Managers and other Clinical Personnel. Webinar Requirements: A computer, phone, etc., with internet accessibility and a telephone line. ØYour presence on the call must be acknowledged at the start of each session. Please log in for the session announce your name loud and clear at the beginning of the session. ØYou will not be able to receive CME credits if you leave the session early. ØAt the end of the Webinar our Training Coordinator will a CME Evaluation Survey. ØAll participants are required to complete and return the CME Evaluation Survey at the end of each session. It may be scanned and ed back to den_bailey@howard.edu, or faxed to: AETC-Capitol Region Telehealth Project (FAX#: ) ATTN: Project Coordinator. Please indicate in your or FAX if you would like to receive CMEs.

6 TEST YOUR KNOWLEDGE 6

7 TestYour Knowledge Question #1 HIV Accelerates HCV related Fibrosis: A.True B. False

8 TestYour Knowledge Question #2 The following factors are associated with HIV/HCV Fibrosis Progression: A. Alcohol Consumption B. Male Gender C. Age D. Multiple Transfusions

9 TestYour Knowledge Question #3 HCV antibody test means the person is still infectious: A. True B. False

10 TestYour Knowledge Question #4 Which of the following is true about Hepatitis C? A. Cure protects for a life time B. Cannot be treated while treating HIV C. Cannot be treated in someone with cirrhosis D. Can be cured in as little as 8 weeks

11 CARE FOR PATIENTS WITH CHRONIC HCV/HIV COINFECTIONS

12 LEARNING OBJECTIVES 1. Describe the epidemiology of HCV 2. Describe progression of liver disease in the setting of HIV/hepatitis C virus (HCV) coinfection 3. Understand treatment objectives 4. Describe barriers to treatment, including drug-drug interactions

13 EPIDEMIOLOGY Ø Five major types, maybe six minor types Ø Estimated 3.5 million people in the US have chronic HCV Ø Yearly, 17,000 get infected Ø Long-term incubation can eventually result in liver failure, liver cancer Ø Every year approximately 12, 000 die from HCV related liver disease

14 WHERE DOES IT COME FROM? ØIt is typically spread when blood from a person infected with the hepatitis C virus enters the blood stream of a non-infected person. ØYes, and sex Ø Transfusions (before 1982)

15 RISK FACTORS FOR ACQUIRING HCV

16 SYMPTOMS Ø Silent for years Ø Signs of eventual liver damage o Fever o Fatigue o Jaundice o Dark urine o Grey colored stools o Joint pain

17 HIV/HCV COINFECTION ØCompared to HCV monoinfection o Higher rates of susceptibility to mucosal transmission o Higher rates of persistence o Faster rates of fibrosis o Higher rate of cirrhosis o Increased liver related mortality

18 CARE CASCADE IN HCV

19 PROGRESSION OF FIBROSIS IN HCV

20 IMPACT OF HIV COINFECTION

21 Kim and Chung Gastroenterology 2009 HIV ACCELERATES HCV RELATED FIBROSIS

22 FACTORS ASSOCIATED WITH HIV/HCV FIBROSIS PROGRESSION ØCD4 count less than 200 cells/mm 3 ØAlcohol consumption ØOlder age at time of HCV acquisition Di Martino et al Hepatology 2001

23 MODIFIABLE RISK FACTORS FOR DISEASE PROGRESSION Diabetes/ insulin resistance Coinfection with HBV Marijuana

24 IMPACT OF HCV CURE

25 54 Y.O. WITH HCV ANTIBODIES 54 year old man was anti-hcv positive after elevated ALT was noted by the Primary Care Provider. He had a brief history of IDU when in his 20 s, and was now currently a moderate ETOH user, otherwise healthy. HCV RNA was 4 million IU/L; Genotype 1a, ALT 42 IU/ml, AST 65 IU/ml, TB 1.6 mg/dl, Alb 3.9 mg/dl, Hgb 13.4 mg/dl, PLT 110,000, Creatinine 1.2 mg/dl

26 54 Y.O. WITH HCV ANTIBODIES Which of the following is the net appropriate step: 1. Treat with oral regimen for 12 weeks 2. Check HCV 1a resistance test 3. Elastography 4. Confirm HCV antibody test

27 STAGING IS NEEDED FOR CHRONIC HCV Accepted Staging Methods 1. Liver biopsy 2. Blood markers 3. Elastography 4. Combination of 1-3 Not for Staging 1. Viral Load 2. HCV genotype 3. Ultrasound 4. CT scan or MRI

28 VALIDITY OF NONINVASIVE TESTS FOR DETECTING CIRRHOSIS Test % Sens %Spec AUROC Pos LR Neg LR Fibrotest > Fibrotest> FIB4> APRI Elastography

29 54 Y.O. WITH HCV ANTIBODIES Elastography is 16.4 kpa FIB 4 = (Age x AST)/(PLT x ALT) FIB 4 = (54 x 65)/(110 x 42) = 4.92 What is the next step?

30 MANAGEMENT OF HCV WITH F Need US (or CT/MRI) to rule out Hepatocellular Carcinoma 2. Need UGI to assess for Esophageal Varicies 3. Need to assess if compensated CPT: no encephalopathy or ascites; bilirubin <2 mg/dl, albumin >3.5 g/dl, and INR< Treat MELD = 3.8*log(serum bilirubin[mg/dl]) *log(INR) + 9.6log(serum creatinine [mg/dl]) + 6.4

31 DOES HIV CHANGE THINGS? You are called back and told the patient is HIV coinfected and on TDF/FTC and darunavir/retonavir. What does that change? 1. Treat for 24 weeks vs 12 weeks 2. Use SOF/LDV to avoid drug interactions 3. Notify the patient treatment is the same, but chances of SVR is 85% instead of 95% 4. Treat with elbasvir/grazoprevir if no resistance

32 HCV AND HIV Treatment responses are the same Drug interaction often define treatment 1. HIV integrase inhibitors generally ok 2. HCV SOF Ok 3. HCV PI avoid HIV PI, efavirenz and cobistat 4. HCV LDV and VEL PPI reduces absorption

33 HCV GUIDELINES Test all born and with risk For positives Vaccinate HAV and HBV Counsel regarding alcohol and transmission Stage Treat

34 54 YEAR OLD WITH HCV AND HIV Ultrasound and UGI are ok and you recommend treatment but he wants to know why. Which of the following is not true? 1. Successful treatment reduces the risk of reinfection 2. Successful treatment reduces the risk of death 3. Successful treatment reduces the risk of Hepatocellular Carcinoma 4. Successful treatment reduces the risk of lever failure

35 THERAPY IN HIV/HCV COINFECTION Ø When compared to HCV monoinfection: o Duration of treatment usually the same o Medication regimens often the same o Adverse events the same (almost none) o OUTCOMES the same o But. Ø Drug-drug interactions may be significant

36 POOR HISTORICAL RESPONSE IN HIV/HCV Poordad F et al, NEJM 2011; 364: vs. Sulkowski et al. Lancet Infect Dis 2013; 13(7): Jacobson I et al, NEJM 2011; 364: vs. Sulkowski et al. Ann Intern Med 2013; 159(2): Antiviral Drugs Advisory Committee Meeting, FDA review, 10/24/13 C208, C216, C206, C212, HPC3007, Dieterich et al. Clin Infect Disease 2014 (epub ahead of print) Lawitz et al. NEJM 2013 versus Torres-Rodriguez et al., IDSA 2013 Osinusi et al., JAMA 2013;310(8): versus Sulkowski et al. JAMA 2014;312(4):

37 EQUIVALENT HIV/HCV RESPONSE TO DAAS Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373: Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370: Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373: Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370: Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir codosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313: Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370: Dieterich D, Rockstroh JK, Orkin C, et al. 7. Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomized, open-label trial. Lancet HIV. 2015;2:e Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015;163:1-13.

38 Naggie et al NEJM ION 4: SOFOSBUVIR/ LEDIPASVIR IN HIV/HCV COINFECTION

39 Naggie et al NEJM ION 4: SOFOSBUVIR/ LEDIPASVIR IN HIV/HCV COINFECTION

40 Naggie et al NEJM ION 4: SOFOSBUVIR/ LEDIPASVIR IN HIV/HCV COINFECTION

41 TAKE HOME: SOFOSBUVIR/LEDIPASVIR ØHCV Genotypes 1, 4 ØSingle pill daily usually 12 weeks ØEffective in treatment naïve, experienced, cirrhotic, non cirrhotic ØSome Drug-Drug interactions

42 Rockstroh et al Lancet HIV C-EDGE COINFECTION: ELBASVIR/GRAZOPREVIR IN HIV/HCV COINFECTION

43 C-EDGE COINFECTION ELBASVIR/GRAZOPREVIR IN HIV/HCV COINFECTION Rockstroh et al Lancet HIV

44 Zeuzem et al Ann Int Med ELBASVIR/GRAZOPREVIR EFFECT OF BASELINE RAVS

45 Zeuzem et al Ann Int Med ELBASVIR/GRAZOPREVIR BASELINE NS5A RAVS

46 Roth et al Lancet ELBASVIR/ GRAZOPREVIR IN RENAL DISEASE

47 TAKE HOME: GRAZOPREVIR ELBASVIR Ø Genotype 1 and 4 Ø Single pill daily Ø Effective in treatment naïve, experienced, cirrhotic, non cirrhotic Ø Some Drug-Drug Interactions Ø Need to check baseline RAVs in 1a Ø Useful in Renal disease, including ESRD o No dose adjustment Ø Cost?

48 Wyles et al NEJM ALLY -2 DACLATASVIR/ SOFOSBUVIR GENOTYPE IN HIV/HCV COINFECTION

49 Wyles et al NEJM ALLY-2 DACLATASVIR/SOFOSBUVIR GENOTYPE 1 HIV/HCV COINFECTION

50 COMPARISON OF ART ALLOWED IN PHASE 3 CLINICAL TRIALS

51 TAKE HOME: DACLATASVIR/ SOFOSBUVIR ØGenotypes 1 through 4 Ø2 pills a day ØSome Drug-Drug interactions but can adjust dose of DCV ØMay be expensive o 2 separate manufacturers

52 DRUG-DRUG INTERACTIONS Simeprevir Sofosbuvir Ledipasvir Daclatasvir Paritaprevir, ritonavir, ombitasvir plus dasabuvir (PrOD) Paritaprevir, ritonavir, ombitasvir (PrO) Grazoprevir/ Elbasvir Ritonavir-boosted atazanavir Ritonavir- boosted darunavir Ritonavir-boosted lopinavir Ritonavir-boosted tipranavir No data No data Ledipasvir ; atazanavir a (okay with TAF not TDF) Simeprevir ; darunavir Efavirenz Simeprevir ; efavirenz Sofosbuvir ; darunavir Ledipasvir, darunavir a (okay with TAF not TDF) Daclatasvir b Paritaprevir ; atazanavir Daclatasvir ; darunavir Paritaprevir /; darunavir No data No data No data a Daclatasvir ; lopinavir Paritaprevir ; lopinavir Paritaprevir ; atazanavir Paritaprevir ; darunavir Paritaprevir ; lopinavir Grazoprevir ; elbasvir ; atazanavir Grazoprevir ; elbasvir ; darunavir Grazoprevir ; elbasvir ; lopinavir No data No data No data No data No data No data No data Sofosbuvir ; efavirenz Ledipasvir ; Daclatasvir b No pharmacokinetic data c No data Grazoprevir ; efavirenz a elbasvir ; efavirenz Rilpivirine Simeprevir ; rilpivirine Sofosbuvir ; rilpivirine Ledipasvir ; rilpivirine No data Paritaprevir ; rilpivirine No data Grazoprevir ; elbasvir ; rilpivirine Etravirine No data No data No data Daclatasvir b No data No data No data Raltegravir Simeprevir ; raltegravir Cobicistat-boosted elvitegravir Sofosbuvir ; raltegravir No data Cobicistat a ; sofosbuvir (okay with TAF not TDF) Ledipasvir ; raltegravir Cobicistat ; ledipasvir a (okay with TAF not TDF) No data PrOD ; raltegravir PrO ; raltegravir Grazoprevir ; elbasvir ; raltegravir No data No data No data No data Dolutegravir No data No data Ledipasvir ; dolutegravir Daclatasvir ; dolutegravir Paritaprevir ; dolutegravir No data Grazoprevir ; elbasvir ; dolutegravir Maraviroc No data No data No data No data No data No data No data Tenofovir disoproxil fumarate Simeprevir ; tenofovir Sofosbuvir ; tenofovir Ledipasvir ; tenofovir Daclatasvir ; tenofovir PrOD ; tenofovir Pro ; tenofovir Grazoprevir ; elbasvir ; tenofovir

53 DRUG-DRUG INTERACTIONS

54 KEY POINTS IN TREATING HCV IN HIV/HCV COINFECTION Ø High priority due to faster progression to cirrhosis Ø DAA therapy is highly effective o Drug-Drug Interactions may guide therapy o Cost will guide therapy Ø Many HCV regimens will NOT require alteration in HIV therapy Ø If change in HIV regimen is needed remember: o HCV therapy is short, HIV is very long o Ensure patient is stable on new HIV regimen x three-six months before treating HCV

55 TEST YOUR KNOWLEDGE 55

56 TestYour Knowledge Question #5 HIV Accelerates HCV related Fibrosis: A.True B. False

57 TestYour Knowledge Question #6 The following factors are associated with HIV/HCV Fibrosis Progression: A. Alcohol Consumption B. Male Gender C. Age D. Multiple Transfusions

58 TestYour Knowledge Question #7 HCV antibody test means the person is still infectious: A. True B. False

59 TestYour Knowledge Question #8 Which of the following is true about Hepatitis C? A. Cure protects for a life time B. Cannot be treated while treating HIV C. Cannot be treated in someone with cirrhosis D. Can be cured in as little as 8 weeks

60 Howard University HURB th Street NW, 2 nd Floor Washington, DC (Office) (Fax) As a Reminder: At the end of the Webinar, All participants are required to complete and return the CME Evaluation Survey. It may be scanned and ed back to den_bailey@howard.edu, or faxed to: AETC-Capitol Region Telehealth Center (FAX#: ) ATTN: Training Coordinator. Please indicate in your or FAX if you would like to receive CMEs.