Treatment of Chronic HCV with Direct-Acting Antivirals (DAAs) hcvguidelinesny

1. Treatment of Chronic HCV with Direct-Acting Antivirals (DAAs) www.hcvguidelinesny.org

2. Purpose of this Guideline • Increase the number of NYS residents with chronic HCV infection treated for and cured of HCV. • Increase compliance with 2014 NYS public health law that requires HCV antibody screening to be offered to every individual born between 1945 and 1965 who receives healthcare services from an MD, PA, or NP in a primary care or inpatient hospital setting. • Reduce the growing burden of morbidity and mortality associated with chronic HCV. • Integrate evidence-based clinical recommendations into the HCV-related implementation strategies of the NYS Ending the Epidemic initiative, which seeks to end the AIDS epidemic in NYS by the end of 2020. NYSDOH AIDS Institute Clinical Guidelines Program

3. Cohort-Based Screening: NYS Law • Beginning in January 2014, NYS public health law requires that HCV antibody screening be offered to every individual born between 1945 and 1965 who receives healthcare services from an MD, PA, or NP in a primary care or inpatient hospital setting. • HCV screening is required unless the healthcare practitioner believes that the individual: • Is being treated for a life-threatening emergency, or • Has previously been offered or has received an HCV screening test, or • Lacks capacity to consent to an HCV screening test NYSDO AIDS Institute Clinical Guidelines Program

4. Recommendation: Screening of Pregnant Patients • Clinicians should perform HCV screening in all patients who are pregnant or planning to get pregnant. NYSDOH AIDS Institute Clinical Guidelines Program

5. Recommendation: Risk-Based Screening NYSDOH AIDS Institute Clinical Guidelines Program

6. Recommendation: Annual Screening • Clinicians should offer HCV screening at least annuallyto individuals who are not known to have HCV infection and: • Use injection drugs (A2) • Use intranasal drugs (A2) • Receive current long-term hemodialysis (A2) • Are men who have sex with men and others who: • Engage in receptive anal sex and other behaviors that may tear mucous membranes (A2) • Have multiple sex partners (A2) • Are taking PrEP (A3) • Are transgender women (B3) • Engage in sex while using recreational mind-altering substances, particularly methamphetamine (A2) • Have been diagnosed with another STI in the last 12 months (A2) NYSDOH AIDS Institute Clinical Guidelines Program

7. Recommendation: Screening for Occupational or Other HCV Exposure • Clinicians should perform HCV screening for individuals who are not known to have HCV infection and have a possible exposure in a healthcare setting, including any of the following: • Break in the skin caused by a sharp object (A2) • Bite that has produced blood (A2) • Body fluid splashed on a mucosal surface (A3) • Exposed non-intact skin(A3) NYSDOH AIDS Institute Clinical Guidelines Program

8. Key Points: At-Risk Adolescents and Young Adults • HCV screening should be offered to at-risk adolescents and young adults. • Parallel epidemics of HCV infection and opioid use have been observed among young male and female injection drug users, primarily in suburban and rural areas. NYSDOH AIDS Institute Clinical Guidelines Program

9. Diagnosing HCV InfectionCDC. MMWR. 2013;62(18) Notes: * For people who might have been exposed to HCV within the past 6 months, testing for HCV RNA or follow-up testing for HCV antibody is recommended. For people who are immunocompromised, testing for HCV RNA can be considered. † To differentiate past, resolved HCV infection from biologic false positivity for HCV antibody, testing with another HCV antibody assay can be considered. Repeat HCV RNA testing if the person tested is suspected to have had HCV exposure within the past 6 months or has clinical evidence of HCV disease, or if there is concern regarding the handling or storage of the test specimen. NYSDOH AIDS Institute Clinical Guidelines Program

10. Recommendations: Acute HCV Infection • Clinicians should suspect acute HCV infection if a patient who had a negative antibody test documented within the previous 6 months has a new positive antibody test or has detectable HCV RNA in the absence of a positive antibody test. (A3) • Clinicians should not prescribe pre- or post-exposure prophylaxis to prevent HCV infection. (A1) • If chronic HCV infection is established, clinicians should evaluate patients for treatment. (A1) • Clinicians should screen all patients with possible acute HCV infection for HIV, HAV, and HBV infections, given the similar risk factors for acquisition. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

11. Pretreatment History and Physical Exam Physical Exam: • Presence or absence of ankle edema, abdominal veins, jaundice, palmar erythema, gynecomastia, spider telangiectasia, ascites, encephalopathy, and asterixis • Presence or absence of physical signs related to extrahepatic manifestations of HCV, such as porphyria cutanea tarda, vasculitis, or lichen planus • Liver size by palpation or auscultation • Cardiac status History: • Previous HCV treatment • History of hepatic decompensation • Current meds • Pregnancy status/plans • Vaccination status for HAV, HBV, PPSV23 (for HPV), and annual influenza • HIV infection • History of renal disease NYSDOH AIDS Institute Clinical Guidelines Program

12. Pretreatment Assessment • History or active use of alcohol, tobacco, marijuana, and other substances is not a contraindication to HCV treatment unless the use is believed to interfere with adherence. • If stabilized, mental health disorders are not contraindications to HCV treatment. • Though HCV treatment is relatively short in duration, assessing a patient’s readiness for treatment and ability to adhere to medications and medical appointments before initiating DAA therapy is essential. NYSDOH AIDS Institute Clinical Guidelines Program

13. Baseline Laboratory Testing • HAV and HBV Abs • HIV • Urinalysis • Fibrosis serum markers • Serum electrolytes w/ creatinine • HCV RNA quantification • HCV genotype/subtype • CBC • Hepatic function panel • INR • Pregnancy NYSDOH AIDS Institute Clinical Guidelines Program

14. Recommendations: Fibrosis Assessment • Clinicians should assess the degree of fibrosis in patients with chronic HCV infection to aid in determining the following (A1): • Need for pretreatment screening for varices and hepatocellular carcinoma • Duration of antiviral treatment • Need to include ribavirin (RBV) in the treatment regimen • Need for post-treatment follow-up • Clinicians should assess patients with chronic HCV infection for decompensated liver disease. (A1) • Clinicians should refer patients with decompensated cirrhosis to a liver disease specialist. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

15. Methods for Staging Fibrosis NYSDOH AIDS Institute Clinical Guidelines Program

16. Recommendations: Pregnancy and HCV • Clinicians should perform HCV screening in all patients who are pregnant or planning to get pregnant. (B3) • Clinicians should advise pregnant patients with HCV to defer treatment with DAAs until they are no longer pregnant or breastfeeding. (A2) • If an individual with HCV becomes pregnant during DAA treatment, clinicians should (A3): • Advise that the use of DAAs is not currently recommended during pregnancy because no data are currently available on the effects of medications on the fetus. • Discuss the risks and benefits of continuing treatment. NYSDOH AIDS Institute Clinical Guidelines Program

17. Recommendations: Pregnancy and HCV, continued • Clinicians should refer pregnant patients who are diagnosed with HCV (HCV antibody positive and HCV RNA detectable), or who are known to have HCV and become pregnant before or during DAA treatment, to a specialist experienced in counseling about HCV in pregnancy. (A3) Specialists may include, but are not limited to, hepatologists, gastroenterologists, ID specialists, or high-risk OBs. • If a pregnant patient with HCV has a substance use disorder, the clinician should provide substance use treatment, including harm reduction services, or refer the patient for these services. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

18. Recommendations: Postpartum Patients • Clinicians should advise pregnant and postpartum individuals with HCV monoinfection that breastfeeding is considered safe, and HCV is not transmitted through breastmilk. (B3) • Clinicians should advise patients that if they have or develop cracked or bleeding nipples, breastfeeding should be discontinued and milk should be expressed and discarded until bleeding has resolved. (B3) • Clinicians should refer infants born to individuals with HCV to clinicians with experience in HCV care for further counseling and testing, and notify the clinician of the mother’s HCV status. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

19. Pregnancy and Stigma • It is important to recognize and acknowledge the influence of stigma toward pregnant individuals with HCV. • The effects of stigma cannot be underestimated. • One cannot assume that HCV infection is associated with current or past injection drug use. Such assumptions can result in personal, family, and legal consequences for the patient, particularly among pregnant individuals. NYSDOH AIDS Institute Clinical Guidelines Program

20. Recommendations: DAA Treatment Considerations • Clinicians should assess creatinine clearance (CrCl) before initiating DAAs. (A1) • Clinicians new to HCV treatment should consult a liver disease or experienced viral hepatitis specialist when treating patients who: • Have severe renal impairment (CrCl <30 mL/min) and/or are undergoing hemodialysis. (A3) • Require retreatment after treatment failure with any DAA regimen. (B3) • Clinicians should prescribe RBV with caution for patients with a CrCl <50 mL/min. (A1) • If prescribed, a reduced dose of 200 mg per day is required. • Regimens with no RBV can be prescribed without dose adjustments for patients with a CrCl ≥30 mL/min. NYSDOH AIDS Institute Clinical Guidelines Program

21. Recommendations: DAA Treatment Contraindications • Clinicians should not use RBV to treat: • Female or male patients planning conception within 6 months of the last dose of RBV. (A2) • Male patients who have pregnant partners. (A2) NYSDOH AIDS Institute Clinical Guidelines Program

22. Treatment Recommendations • The guideline presents treatment options by HCV genotype, the patient’s cirrhosis status, and previous HCV treatment. • Each list of options is in alphabetical order, not in order of preference. • No regimens are preferred over others because insufficient data exist for direct comparisons. • Except where indicated, all treatment recommendations are rated A1: strong recommendations with 1 or more randomized trials with clinical outcomes and/or validated laboratory endpoints supporting the recommendation. • Consult the guideline for full treatment recommendations. NYSDOH AIDS Institute Clinical Guidelines Program

23. “Undetectable” or “Indeterminate” Genotype • Rarely, HCV genotype results are “undetectable” or “indeterminate” for patients with detectable HCV viral load. • These results are consistent with active HCV infection; assess patients for degree of fibrosis. • DAA treatment options: • Repeat the genotype and HCV viral load tests in 3 months and decide or • Initiate pan-genotypic regimen (GLE/PIB or SOF/VEL) at dose and duration recommended for treatment-naive patients with genotype 3 HCV, based on degree of fibrosis. NYSDOH AIDS Institute Clinical Guidelines Program

24. Genotype 1a, Treatment-Naive NYSDOH AIDS Institute Clinical Guidelines Program

25. Genotype 1a, Prior Failure w/ PEG-IFN + RBV NYSDOH AIDS Institute Clinical Guidelines Program

26. Genotype 1b, Treatment-Naive NYSDOH AIDS Institute Clinical Guidelines Program

27. Genotype 1b, Prior Failure w/ PEG-IFN + RBV NYSDOH AIDS Institute Clinical Guidelines Program

28. Genotype 2 NYSDOH AIDS Institute Clinical Guidelines Program

29. Genotype 3 NYSDOH AIDS Institute Clinical Guidelines Program

30. Genotype 4, Treatment-Naive NYSDOH AIDS Institute Clinical Guidelines Program

31. Genotype 4, Prior Failure w/ PEG-IFN + RBV NYSDOH AIDS Institute Clinical Guidelines Program

32. Genotype 5 NYSDOH AIDS Institute Clinical Guidelines Program

33. Genotype 6 NYSDOH AIDS Institute Clinical Guidelines Program

34. Retreatment Options after DAA Failure NYSDOH AIDS Institute Clinical Guidelines Program

35. Retreatment Options after DAA Failure NYSDOH AIDS Institute Clinical Guidelines Program

36. Retreatment Options after DAA Failure NYSDOH AIDS Institute Clinical Guidelines Program

37. Retreatment Options after DAA Failure NYSDOH AIDS Institute Clinical Guidelines Program

38. Recommendations: Monitoring • While patients are taking RBV, clinicians should perform hemoglobin testing at weeks 2 and 4 of treatment and every 4 weeks thereafter until therapy is complete. (A1) • For patients taking GLE/PIB or ELB/GRZ, clinicians should monitor ALT 4 weeks after initiating treatment and continue according to the drug’s prescribing information. (A3) • In patients who are HBsAg positive and have no detectable HBV DNA, clinicians should monitor for HBV reactivation by performing AST, ALT, and HBV DNA tests every 4 weeks during HCV treatment. (A3) • Clinicians new to HCV treatment should consult liver disease or experienced viral hepatitis specialist for further evaluation of patients who develop detectable HBV DNA. (A3) • If a patient becomes pregnant during therapy with a regimen containing RBV, clinicians should stop the RBV. (A1) • If a patient becomes pregnant during therapy with any DAA regimen, clinicians should discuss the benefits and risks of using DAAs during pregnancy. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

39. DAA Adverse Events NYSDOH AIDS Institute Clinical Guidelines Program

40. Key Points: Drug Interactions with DAAs • The guideline has extensive tables by drug or drug combination on interactions between DAAs and common medications and between DAAs and ART. • Please consult the full guideline or other current resources. NYSDOH AIDS Institute Clinical Guidelines Program

41. DAA Drug Interactions: Other Resources • AASLD/IDSA HCV guidance: https://www.hcvguidelines.org/ • University of Liverpool HEP Drug Interactions: https://www.hep-druginteractions.org/ • Northeast Caribbean AETC Antiretroviral Clinical Support Tools: DAA Drug Interactions Quick Guides for Clinicians: http://necaaetc.org/content/clinical-support-tools NYSDOH AIDS Institute Clinical Guidelines Program

42. Recommendations: Evaluating Response to Treatment • Clinicians should perform HCV RNA testing 12 weeks after treatment is complete to verify that an SVR is achieved. (A1) • If SVR is achieved, as established by undetectable HCV RNA at 12 weeks after treatment, clinicians should: • Inform their patients that the HCV infection has been cured. (A2) • Explain the risk of HCV reinfection and that HCV antibodies are not protective against reinfection. (A1) • To assess reinfection in patients with ongoing risk factors, clinicians should perform follow-up screening with HCV RNA testing (not HCV antibody testing) at least annually, even with a history of an SVR. (A1) • If HCV RNA is detectable at 12 weeks after treatment, clinicians should: • Inform patients that treatment has failed. (A1) • If new to HCV treatment, consult with a liver disease or viral hepatitis specialist for retreatment evaluation. (B3) NYSDOH AIDS Institute Clinical Guidelines Program

43. Recommendations: Follow-Up in Pregnancy • For patients taking RBV-containing HCV regimens, clinicians should: • Advise male and female patients to take extreme care to avoid pregnancy for 6 months after completion of therapy. (A2) • Counsel female and male patients on effective contraceptive use. (A2) • If a patient becomes pregnant within 6 months of completing an RBV-containing HCV treatment, clinicians should discuss the risks of using DAAs and RBV during pregnancy. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

44. Recommendations: Follow-Up for Patients with Persistent Liver Disease • Clinicians should evaluate patients with persistent abnormal transaminase levels after SVR for other causes of liver disease and consult with a liver disease specialist. (A3) • In patients with underlying bridging fibrosis or cirrhosis, clinicians should screen for hepatocellular carcinoma every 6 months. (A1) NYSDOH AIDS Institute Clinical Guidelines Program

45. HIV/HCV Coinfection • Treatment of chronic HCV in patients with HIV requires attention to drug-drug interactions between DAAs and ARVs and to a few other HIV-specific treatment issues (see full guideline). • Otherwise, clinicians should follow the recommendations for the assessment, treatment, monitoring, and follow-up of patients with HCV monoinfection and consult with an experienced HIV care provider or a liver disease or viral hepatitis specialist as needed. NYSDOH AIDS Institute Clinical Guidelines Program

46. Recommendations: HCV Screening in Patients with HIV • Clinicians should perform HCV screening at least once for patients with HIV; after that, decisions to screen should be based on any ongoing risk factors for HCV infection. (A2) • In patients with HIV who have CD4 counts below 200 cells/mm3 and elevated ALT, clinicians should perform HCV RNA testing along with HCV antibody testing to evaluate for HCV infection. (A2) • If an adjustment in ART is required for compatibility with HCV treatment in patients who are HBV sAg positive, clinicians should maintain use of TDF or TAF as part of the patient’s ART regimen. (A1) NYSDOH AIDS Institute Clinical Guidelines Program

47. Recommendations: HBV Screening in Patients with HIV • In patients who exhibit a pattern of cAb positivity, defined as cAb positive with sAg negative and sAb negative, clinicians should: • Perform HBV DNA testing to assess for active HBV infection. (A1) • Vaccinate patients who have a negative HBV DNA test. (B3) NYSDOH AIDS Institute Clinical Guidelines Program

48. Recommendations: Treating Patients with HIV/HCV • Clinicians should: • Recommend initiation of ART for any patient with HIV/HCV who is not already taking ART. (A1) • Not exclude patients with CD4 counts <200 cells/mm3 from HCV treatment. (A3) • Choose a DAA drug regimen that will not cause adverse DAA-ARV drug-drug interactions. (A3) • Prescribe DAA regimens for a minimum of 12 weeks in patients with HIV/HCV coinfection. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

49. Recommendations: HIV/HCV ART Regimen • Clinicians should consult with an experienced HIV care provider if a patient’s ART regimen must be changed to accommodate simultaneous treatment of HCV infection. (A3) • When prescribing LED or VEL to patients taking TDF, clinicians should: • Substitute TAF for TDF, particularly when the CrCl is <50 mL/min or the regimen also includes COBI or RTV (A3), OR • Substitute ABC if the patient is HLA B*5701 negative and does not have HBV sAg positive, and if the patient has no evidence of prior HIV resistance to ABC (A3), OR • Choose a different DAA regimen. (A3) NYSDOH AIDS Institute Clinical Guidelines Program

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