1. Clinician Consultation Center Indian Health Services California Consortium for Urban Indian Health Hepatitis C Warmline Joanna Eveland, MD Brenda Goldhammer, MPH

2. The Clinician Consultation Center (CCC) at the University of California at San Francisco provides immediate, state-of-the-art HIV/AIDS clinical consultation to health care providers (physicians, nurse practitioners, physician assistants, pharmacists and other health care professionals) across the country through four telephone and online consultation services: HIV/AIDS Management Consultation Service: 6:00 a.m.-5:00 p.m. PST Perinatal HIV Consultation and Referral Service: 24/7 Post-Exposure Prophylaxis Consultation Service(PEPline): 6:00 am – 11:00 pm PST Pre-Exposure Prophylaxis Consultation Service (PrEPline): 6:00 a.m.-5:00 p.m. PST Health Resources and Services Administration (HRSA) HIV/AIDS Bureau AIDS Education and Training Centers (AETCs) and Centers for Disease Control and Prevention (CDC) Clinician Consultation Center

3. What it is: A national, cost-free telephone service providing confidential expert advice on HCV mono- and co-infection for CCUIH/IHS clinicians. Up-to-date, clinically supported options and advice on testing, prevention, and treatment, including follow-up advice for challenging or ongoing clinical management scenarios. Who it’s for: IHS/CCUIH clinicians of any experience level who provide primary care and specialty HIV and/or HCV care, and who have general informational or patient-specific questions on HIV or HCV management. What to expect: Consultation from clinicians, hepatologists, and clinical pharmacists with expertise in HIV and HCV care. Advice is based on Federal treatment guidelines, current medical literature, and clinical best practices. When it’s available: 6 a.m. – 5 p.m. PST, Monday through Friday. Initial responses will be provided within one business day of the call. On nights, weekends, and holidays, calls will be routed to a voice mail system and returned the next business day. IHS/CCUIH HIV and HCV Clinical Consultation Service For HIV Consultation: 1-800-933-3413 For Hepatitis C Consultation: 1-844-437-4636

4. Clinical team blend of… Expert knowledge Primary care foundation Non-judgmental consultation Multidisciplinary approach CCC Consultations

5. Answer caller’s questions with evidence-based responses. Share expert opinion in cases where gray area exists in guidelines. Provide useful references and resources. Build caller’s capacity to manage similar cases in the future. Consultation Goals

6. Expanded HCV screening Treatment is evolving quickly More treatment options, more complexity New issues around cost and access What can the HCV Clinical Consultation Service offer you? Help in a changing treatment landscape

7. History of HCV Treatment: In a New Era

8. Helping you to stay aware of new HCV Treatments

9. Screening for HCV (and interpreting tests) Determining liver disease severity Preparing for treatment Choosing a regimen Topics for the HCV Clinical Consultation Service: Before Treatment

10. Dosing and duration Monitoring Drug interactions Access Complications Topics for the HCV Clinical Consultation Service: During Treatment

11. Management of Liver Cirrhosis Treatment of Special Populations HIV co-infected Pregnancy Kidney failure Substance abuse Topics for the HCV Clinical Consultation Service: Care for Complex Patients

12. Awareness of unique issues faced by Native Populations An understanding of HCV as a “broken spirit disease” Clinical experience working with underserved/minority communities Able to discuss addiction, trauma, poverty as related to HCV treatment Cultural Competency

13. Topics for the HCV Clinical Consultation Service: Sample Questions My patient is 4 weeks into treatment and the HCV viral load is still detectable! Should I stop treatment? What treatment do I pick for my patient with HCV and cirrhosis? My patient’s HCV antibody test just came back positive. What do I do next?

14. Topics for the HCV Clinical Consultation Service: Sample Consult What HCV treatment regimen should I pick for my newly diagnosed patient? He also has diabetes. Consult with Clinical Pharmacist on drug interactions with diabetes and HCV medications Discuss the “question behind the question”: Does this patient have liver cirrhosis? Consult with HCV specialist on treatment options Share treatment guidelines and other educational resources

15. Patient demographics Treatment history HCV genotype and viral load Other recent labs and imaging for staging PMHx, Meds, Allergies, SHx Questions for us Information for a Productive Consult

16. 58 y.o. male with GT 1a infection and compensated cirrhosis Treated from March-June 2015 with Sofosbuvir/Ledipasvir + Ribavirin X 12 weeks Failed treatment: HCV Viral load became undetectable 8 wks into treatment but then relapsed 12 wks post treatment Recent Case

17. Case Continued Labs

18. Should this patient be retreated with combo of Sofosbuvir/Simeprevir? When will next generation of HCV medications be available? Questions from Caller 18

19. How do we interpret HCV resistance testing? How do we manage treatment failure with HCV Direct Acting Agents (DAAs)? Does this patient need to be treated right away? “The Questions behind the Question” 19

20. The Y93C mutation confers resistance to NS5A inhibitors Ledipasvir and Daclatasvir. Check for Q80K (NS3 inhibitor Resistant Associated Variant- RAV) before considering Simepravir. Re-check his HCV genotype as minor species variants may have appeared after treatment. Clinician Response: Managing Resistance

21. Per AASLD/IDSA guidelines, for cirrhotic patients requiring urgent treatment who have NS5A inhibitor RAVs detected and who do not have NS3 inhibitor RAVs detected, treatment with Simeprevir/Sofosbuvir/Riba for 24 weeks is recommended. Clinician Response: Treatment Regimen

22. However, if the patient fails this regimen with NS3 resistance, his future treatment options will be very limited. If no evidence of decompensation, may be reasonable to defer treatment awaiting more data. Another option is retreatment through a clinical trial- referred caller to local trial currently enrolling patients with DAA failure. Clinician Response Continued: Caveats

23. Spoke directly with Merck headquarters. Fixed dose combination of Grazoprevir/Elbasvir has received breakthrough therapy designation and FDA should rule by Jan. 2016 However, this combo has not been evaluated in DAA treatment failures other than a small Phase II trial called C-EDGE. When Will New Drugs be Out?

24. Drugs in the pipeline more relevant to this patient are actually earlier in development. Both Gilead and Merck are developing "triplet combinations" consisting of a HCV nucleoside inhibitor, second generation NS5a inhibitor, and 3rd or 4th generation HCV Protease Inhibitor. Second gen NS5a inhibitors (i.e. Gilead’s 5816) will hopefully will retain activity against resistant virus The earliest likely approval is late 2016. Newer New Drugs

25. Questions? Comments? Concerns?

26. Thank you!