Contemporary Management of HIV-HCV Coinfection

Transcription

1 Contemporary Management of HIV-HCV Coinfection Elizabeth Sherman, PharmD, AAHIVP Faculty, South Florida - Southeast AIDS Education & Training Center HIV/AIDS Clinical Pharmacist, Memorial Healthcare System Assistant Professor, Nova Southeastern University esherman@nova.edu

2 Disclosures The activity planners and speakers do not have any financial relationships with commercial entities to disclose. The speakers will not discuss any off-label use or investigational product during the program. This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation

3 Learning Objectives Apply current guidelines on hepatitis C virus (HCV) screening Manage patients with HCV infection while recognizing adverse effects and drug interactions Counsel patients regarding current HCV treatment options, timing of treatment, and key characteristics of current regimens

4 Introduction

5 Chronic Hepatitis C Virus (HCV) Is a Progressive Disease HEALTHY LIVER FIBROTIC LIVER CIRRHOTIC LIVER Chronic HCV frequently has few or no symptoms and can progress without signs for decades [1] Most patients with chronic HCV are 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:

6 HCV in the US: Gaps in Current Practice % 80 Pts (%) % 43% 27% 20 17% 16% 9% 0 Chronic HCV Infected Diagnosed and Aware Access to Outpatient Care HCV RNA Confirmed Underwent Liver Biopsy Prescribed HCV Treatment Achieved Sustained Viral Response n = 3,500,000 1,743,000 1,514, , , , ,859 Yehia BR, et al. PLoS One. 2014;9:e

7 Current All-Oral Therapies Highly Effective, Simple, Well Tolerated Standard Interferon (IFN) 1991 Ribavirin (RBV) Peginterferon (pegifn) Direct-Acting Antivirals (DAAs) All-Oral Therapy Current IFN 6 Mos IFN 12 Mos IFN/RBV 6 Mos IFN/RBV 12 Mos PegIFN 12 Mos PegIFN/RBV 12 Mos PegIFN/ RBV + DAA DAA + RBV ± PegIFN All Oral DAA± RBV

8 Case 1: When and How to Screen for Hepatitis

9 Case 1: 56-Yr-Old Woman Presenting to Primary Care A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician She is not aware of having been tested for HCV infection previously

10 CDC, USPSTF, and AASLD/IDSA HCV Screening Recommendations Population Recommendation Age One-time screening is recommended for persons born between 1945 and 1965, without ascertainment of HCV risk [1-3] Risk One-time screening is recommended for persons with these risk factors [1,3] : History of illicit injection drug use (IDU) or intranasal illicit drug use History of long-term hemodialysis Receiving a tattoo in an unregulated facility/setting Healthcare workers upon accidental exposure Children born to anti-hcv positive mothers History of transfusion with blood or organ transplantation Were ever in prison HIV infection Chronic liver disease/hepatitis with unknown cause, including elevated liver enzymes Annual screening is recommended for current IDUs and HIV-infected MSM [3] 1. Smith BD, et al. MMWR Recomm Rep. 2012;61(RR-4): US Preventive Services Task Force. HCV Screening Guidelines AASLD-IDSA. HCV Guidelines 2017.

11 Hepatitis C Prevalence is Increased in Baby Boomers Prevalence of Hepatitis C Antibody Positivity in US Population by Sex by Yr of Birth (NHANES III) 10 Prevalence of Hepatitis C Positive (%) Screening recommended Male Female Yr of Birth Iwasaki K, et al. ISPOR Abstract PG17.

12 Talking to Patients About Hepatitis C Testing Provide rationale for testing Provide reassurance about testing Obtain consent

13 Talking to Patients About Hepatitis C Testing Provide rationale for testing It s common Provide reassurance about testing It s curable Obtain consent If it s alright with you, I would like to test you for hepatitis C today

14 Back to Our Case A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician Routine hepatitis C antibody test: reactive

15 Recommended Testing Sequence for Identifying Current HCV Infection HCV antibody test Reactive HCV RNA test Detected Current HCV infection Provide care or link to care Nonreactive Stop Not detected No current HCV infection Additional testing as appropriate CDC. MMWR Morb Mortal Wkly Rep. 2013;62:

16 Recommendations for Additional Follow-up of Initial HCV Testing Quantitative hepatitis C RNA testing prior to initiation of antiviral therapy to document baseline viral load Testing for hepatitis C genotype all genotypes can be treated, but genotype will guide choice of antiviral therapy AASLD-IDSA. HCV Guidelines 2017.

17 Counseling for HCV-Infected Individuals Prevent HCV Transmission Avoid sharing toothbrushes, dental, shaving equipment Prevent blood contact; do not donate blood Avoid illicit drugs; avoid reusing or sharing drug paraphernalia Risk of sexual transmission is low, except for people with HIV, multiple partners, or STIs Reduce Progression of Liver Disease Test for conditions that accelerate fibrosis (Hepatitis B and HIV) Evaluate for advanced fibrosis Update vaccinations Avoid alcohol

18 Recommendations for When and in Whom to Initiate HCV Treatment Treatment is recommended for all pts with chronic hepatitis C infection, regardless of genotype Except where life expectancy likely to be short despite treatment or transplantation AASLD-IDSA. HCV Guidelines 2017.

19 All-Cause Mortality (%) HCV Virologic Cure Associated with Improved Outcomes P <.001 All-Cause Mortality Without SVR With SVR Yr HR: 0.26 (95% CI: ; P <.001) Liver-Related Mortality or Liver Transplantation (%) Liver-Related Mortality or Liver Transplantation P <.001 Without SVR With SVR Virologic cure does not protect against reinfection van der Meer AJ, et al. JAMA. 2012;308: Yr

20 Fibrosis Staging Determines treatment (e.g., use of ribavirin) and treatment duration Metavir Stage 0-2: No fibrosis or portal fibrosis Metavir Stage 3-4: Advanced fibrosis or cirrhosis Noninvasive strategies: APRI (AST platelet ratio index), FIB-4, FibroSure, FibroScan

21 Case 2 Ongoing Management of HCV

22 Case 2: 45-Yr-Old Man With Hepatitis C Infection A 45-yr-old man visits your office Diagnosed with chronic HCV in 2011, previously treated with peginterferon and ribavirin Noninvasive markers suggest Metavir stage 2 (some fibrosis) Now expresses interest in hepatitis C therapy after hearing positive reports about new oral treatments

23 Case 2: Initial Workup Parameter Coinfections HCV genotype HCV RNA FibroSure Finding HAV negative, HBV negative, HIV negative 1a 3,500,000 IU/mL F2 Parameter Finding WBC 3500 cells/mm 3 Hemoglobin 14 g/dl Platelets 155/μL INR 1.0 Albumin 3.8 mg/dl Total bilirubin 1.2 mg/dl AST 68 IU/mL ALT 64 IU/mL Alk phos 155 IU/mL Creatinine 1.2 mg/dl

24 Many Options in 2017: Current All-Oral Regimens for Hepatitis C Infection Regimen Approved Genotypes Grazoprevir/elbasvir 1, 4 Ombitasvir/paritaprevir/rit onavir Ombitasvir/paritaprevir/rit onavir + dasabuvir Sofosbuvir + daclatasvir 1, 3 Sofosbuvir/ledipasvir 1, 4, 5, 6 Simeprevir + sofosbuvir 1, 4 Sofosbuvir/velpatasvir 1, 2, 3, 4, 5, 6 Sofosbuvir/velpatasvir/vo xilaprevir 4 1 1, 2, 3, 4, 5, 6 Effective options for every genotype Single-pill formulations or 2-pill combinations Effective for all genotypes

25 HCV Drug Targets: Helpful Hints -previr NS3 protease inhibitors -buvir NS5B inhibitors -asvir NS5A inhibitors

26 HCV Treatment: Get to Know Your Patient HCV genotype? Presence of cirrhosis? Previous HCV therapy? Helps tailor: Treatment options Treatment duration Need for ribavirin Key Resource:

27 Adverse Events and Drug-Drug Interactions

28 Adverse Events Newer hepatitis C medications do not have same adverse events as interferon and are generally well tolerated Discuss most common adverse events and management strategies in pre-education session Headaches: nonpharmacologic management strategies, limits of OTC pain relievers and liver disease Anemia: still a concern when ribavirin needed Encourage patients to report bothersome or unusual adverse events

29 Ribavrin Considerations Most patients won t need it! If they do Discuss contraception Check baseline hemoglobin and test for anemia through treatment Counsel on anemia symptoms Know that anemia can be managed for most while completing HCV therapy

30 Pretreatment: Look for Potential Drug Drug Interactions Review all herbals/supplements, prescription and OTC meds, including contraceptives and proton pump inhibitors Ask about PRN usage of other drugs Consult with clinical pharmacist when possible Key Resource:

31 Drug Interactions in the HIV-HCV Coinfected Patient Priority population for treatment SVR rates similar to HCV monoinfected [1,2] In HCV/HIV coinfection, treat HCV as though HCV monoinfected, but consider drug drug interactions [3] Drug drug interactions may require careful selection of HCV regimen or changes in HIV ART regimens Non-HIV providers require collaboration with the patient s HIV provider 1. Naggie S, et al. N Engl J Med. 2015;373: Wyles DL, et al. N Engl J Med. 2015;373: AASLD/IDSA Guidelines. February 2016.

32 SIM + SOF HCV Interactions With ART LDV/ SOF SOF + DCV PTV/RTV/ OBV + DSV PTV/RTV/ OBV EBV/ GZR SOF/ VEL SOF/VEL/ VOX Atazanavir + RTV or COBI Χ Χ Χ Χ Darunavir + RTV or COBI Χ Χ Χ Raltegravir Dolutegravir Elvitegravir/ COBI/FTC/ TDF Χ Χ Χ Χ Χ Elvitegravir/ COBI/ FTC/ TAF Χ Χ* Χ Χ Efavirenz Χ Χ Χ Χ Χ Χ Rilpivirine Χ Χ Abacavir/ lamivudine Emtricitabine/ TDF Emtricitabine/ TAF No clinically significant interaction expected nephrotoxicity nephrotoxicity nephrotoxicity Potential interaction may require adjustment to dosage, timing of administration, or monitoring Χ Do not coadminister

33 Other Selected Potential Drug Drug Interactions with HCV Agents Concomitant Medication SIM/ SOF LDV/ SOF SOF/ DCV PTV/RTV/ OBV + DSV PTV/RTV/ OBV EBV/ GZR SOF/ VEL SOF/ VEL/VOX Acid-reducing agents* X X X X X Amiodarone X X X X X X X Anticonvulsants X X X X X X X X Digoxin X X X X X X Ethinyl estradiol containing products Glucocorticoids X X X X X PDE5 inhibitors X X X X Rifamycin antimicrobials X X X X X X X X St John s wort X X X X X X X X Statins X X X X X X X X X X *eg, proton pump inhibitors such as omeprazole. Including inhaled, intranasal. AASLD/IDSA Guidelines

34 Supporting Patients During Antiviral Therapy Recommendations Offer clinic visits or telephone contact to ensure adherence and to monitor for adverse events and drug interactions CBC, creatinine level, egfr, hepatic function panel at week 4 and as clinically indicated Quantitative HCV RNA at week 4 of treatment and again at 12 wks after completion of treatment (SVR) AASLD-IDSA. HCV Guidelines Key Resource:

35 Post-Treatment Follow-up

36 Characteristic Recommended Follow-up After Hepatitis C Treatment Follow-up No advanced fibrosis (Metavir stage F0-F2) No hepatitis C follow-up Advanced fibrosis (Metavir stage F3 or F4) Twice-yearly ultrasound surveillance for hepatocellular carcinoma If compensated cirrhosis (F4) also test for varices using baseline endoscopy Ongoing hepatitis C risk or unexplained hepatic dysfunction Test for recurrence or reinfection with quantitative hepatitis C RNA assay Persistently abnormal liver tests Test for other causes of liver disease No virologic cure Test for disease progression every 6-12 months with hepatic function panel, CBC, and INR Consider retreatment options

37 Summary Patients born should be screened for HCV infection Know risk-based screening recommendations Virtually all with HCV infection should be treated, regardless of genotype and fibrosis Prevents morbidity, progression of fibrosis, hepatocellular carcinoma Current treatments include pangenotypic and ribavirin-free options > 95% rate of cure for most genotypes Most therapies are 12 wks, ribavirin free, all oral, once daily Many patients can be treated in primary care setting Counsel and monitor for adverse effects and drug interactions

38 This Presentation and resources are made possible by AETC grant award U1OHA29295 from the HIV/AIDS Bureau of the Health Resources Services Administration (HRSA), U. S. Department of Health and Human Services (HHS). The information presented is the consensus of HIV/AIDS specialists within the SEAETC and does not necessarily represent the official views of HRSA/HAB The AIDS Education and Training Center (AETC) Program is the training arm of the Ryan White HIV/AIDS Program. The AETC Program is a national network of leading HIV experts who provide locally based, tailored education, clinical consultation and technical assistance to healthcare professionals and healthcare organizations to integrate high quality, comprehensive care for those living with or affected by HIV.

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