Special Considerations: When and What to Start with Viral Hepatitis Coinfections

1. Special Considerations: When and What to Start with Viral Hepatitis Coinfections Joseph J. Eron, Jr, MDProfessor of MedicineUniversity of North Carolina at Chapel Hill FINAL: 07-20-12

2. Slide #2 HCV and HIV – When and What to Start • RM is a 62 yo AA MSM who had a h/o injection drug use in 1970’s. • He only accepted his sexual orientation in the last 5 years after divorcing his wife. Since that time he has had multiple male sex partners and also consumed more alcohol than his typical 7-10 drinks per week. He has not injected drugs in 40 years. • He presents to you after an evening of drinking when he vomited a modest about of blood

3. Slide #3 HCV and HIV – When and What to Start • He is found to have HCV genotype 1a and an HCV VL of 2,700,000 c/mL, his HBV surface Ag is negative and surface Ab is positive • He is HIV+ with CD4 of 850/µL and VL of 8,000 c/mL • On endoscopy he has small varices and no other abnormalities • His AST is 90 and ALT 110, INR is 1.4 and albumin is 3.3. Plt count is 110. He has no ascites by exam and RUQ US and his liver is small and nodular appearing • His HIV genotype shows K103N

4. Slide #4 HCV and HIV – When and What to Start What is your next step for his HCV after getting him to stop alcohol intake? • Obtain a liver biopsy • Obtain a transient elastography • Obtain an IL28b genotype • None of the above – he needs to be treated no matter what the results are • Something else

5. Slide #5 HCV and HIV – When and What to Start You are confident that he needs HCV treatment but his hepatologist does a biopsy any way. Path is read as F3/4 but when pushed pathologist say more 4 than 3. He has decreased his drinking substantially and is on propranolol. What do you do now? • Begin HCV therapy with interferon alfa and ribavirin lead-in and boceprevir • Begin HCV therapy with telaprevir, interferon alfa, and ribavirin • Begin HIV therapy first • Something else

6. HCV and HIV – When and What to Start TDF/FTC ABC/3TC ZDV/3TC Something else Slide #6 You decide that he should begin HIV therapy first and will start HCV therapy once HIV RNA is suppressed. Which NRTI combination will you choose? (HIV RNA 8,000 c/mL, CD4 850/µL and TDR with K103N)

7. HCV and HIV – When and What to Start FDC TDF/FTC/efavirenz FDC TDF/FTC/ rilpivirine FDC TDF/FTC/cobisistat/elvitegravir FDC TDF/FTC and raltegravir FDC TDF/FTC and atazanavir/r FDC TDF/FTC and darunavir/r Something else Slide #7 You decide that he should begin HIV therapy first and will start HCV therapy once HIV RNA is suppressed. If you chose TDF/FTC which cART regimen would you start? (HIV RNA 8,000 c/mL, CD4 850/µL and TDR with K103N)

8. Slide #8 HCV and HIV – When and What to Start You chose TDF/FTC and raltegravir (despite Dr. Eron’s concern re TDR). What HCV therapy will you start when he gets suppressed? • Interferon alfa and ribavirin lead-in and boceprevir • Telaprevir, interferon alfa, and ribavirin • Wait for the next approved drug (12 months or so) • Something else

9. Slide #9 HCV and HIV – When and What to Start • On HIV therapy HIV RNA falls to < 50 c/mL with 8 weeks and his CD4 increases to 900/µL. • However he presents with nausea and vomiting and his AST rises to 459 and ALT to 600, bilirubin rises slightly to 1.2 (was 0.8) and INR = 1.5.

10. HCV and HIV – When and What to Start Freak and call Jurgen Rockstroh Continue treatment with weekly labs Stop HIV therapy and wait for AST/AST to decline and then restart TDF/FTC ATV/r (or similar) Stop HIV therapy and wait for AST/AST to decline and treat his HCV Get a liver biopsy Something else Slide #10 What do you do?

11. HIV and HBV

12. HBV and HIV – What to Start Robin M is Latina and 35 yo who was recently diagnosed with HIV and HBV. She has had one male partner who is also HIV and HBV infected and unfortunately they do not always use condoms. He is currently suppressed on therapy but previously had failed a regimen of ZDV/3TC and EFV in 2005 or 2006 after several years of therapy. Robin M has been avoiding HIV and HBV testing for fear of a positive test. She has obesity (BMI 34), HTN and DM. Her last BP was 138/88 mmHg on lisinopril (ACE) and her last HgbA1C was 6.5% on metformin. Slide #12

13. Slide #13 HBV and HIV – What to Start • Her CD4 cell counts is 358/µL with an HIV RNA of 320,000 c/mL • Her HBV viral load is 12,000,000 IU/mL and AST is 58 and ALT 70 IU/mL. INR, albumin and platelets are normal • Her eGFR is 40 mL/min and she has 2+ protein and 2+ glc on UA with a urine prot/creatinine ratio of 800

14. Slide #14 HBV and HIV – What to Start A pre-therapy HIV genotype shows M41L and T215D Would you obtain an HBV resistance genotype? • Yes • No • Not sure

15. Slide #15 HBV and HIV – What to Start • You decide to get a HBV resistance test even though you are not 100% sure how it will effect your therapy choice. • The results show the well-desribed rt M204V/I plus rt L180M mutations associated with lamivudine resistance.

16. HBV and HIV – What to Start Which antiviral combination will you begin? FDC EFV/TDF/FTC TDF/FTC every other day with a recommended third agent TDF/FTC every other day with a recommended third agent plus entecavir ABC/3TC daily with a recommended third agent ABC/3TC daily with a recommended third agent plus entecavir Something else Slide #16

17. Slide #17 HBV and HIV – What to Start If you chose to add entecavir what dose would you choose? • 0.5 mg daily • 1.0 mg daily • No tengo la menor idea!