1. Alan Franciscus Executive Director, Hepatitis C Support Project Editor-in-Chief, HCV Advocate— www.hcvadvocate.org Editor-in-Chief, HBV Advocate – www.hbvadvocate.org Follow us on Twitter and Facebook: hcvadvocate hbvadvocate Hepatitis C and HIV/HCV Coinfection www.hcvadvocate.org

2. OVERVIEW OF HEPATITIS C Please hold questions until the end of the first session HIV AND HEPATITIS C – DIFFERENCES AND SIMILARITIES HIV AND HEPATITIS COINFECTION NEW ADVANCES IN HEPATITIS C CARE Agenda www.hcvadvocate.org

3. HCV STATISTICS HCV DIAGNOSTICS HCV TRANSMISSION & PREVENTION HCV SYMPTOMS, DISEASE PROGRESSION, MANAGEMENT HCV TREATMENT Hepatitis C Overview www.hcvadvocate.org

4. Hepatitis C Statistics U.S. Population 1.6% overall  ~4 million Americans infected  3.2 million chronically infected 2.1% Mexican Americans 3.4% African Americans www.hcvadvocate.org

5. Hepatitis C Statistics - Montana Montana  967, 440 x 1.6% = ~15,500 people with HCV in Montana 948 case of hepatitis C (chronic and acute) reported in 2008  Compare to HIV – 895 cases reported since 1985 Highest rates seen in American Indians and persons age 45-54 (2008) www.hcvadvocate.org

6. HCV Diagnostics: Antibody tests HCV Elisa (EIA) Most common antibody test A positive antibody test indicates exposure It does not indicate current hepatitis C infection Orasure HCV Antibody Test – more later www.hcvadvocate.org

7. HC V Diagnostics: Viral Load Tests Viral Load tests  PCR and TMA 5-10 IU/mL  HCV RNA by branched DNA Assay – > 500 IU/mL Why Is a Viral Load Test Important?  To confirm active infection  Helps to predict treatment response  Indication that treatment is working ** Viral load does not correlate with disease progression** www.hcvadvocate.org

8. HCV Diagnostics: Genotype Test Genotypes (1,2,3,4,5,6)  U.S. population  70% genotype 1  30% genotypes 2 & 3 Why Is a Genotype Test Important?  Helps predict treatment response  Dictates treatment duration of 24 or 48 weeks www.hcvadvocate.org

9. HCV Diagnostics: Liver Biopsy Gold Standard for Determining the Health of the Liver  Measure of inflammation  Extent of scarring (if any) Non-invasive methods – not as accurate www.hcvadvocate.org

10. Transmission & Prevention Shared NeedlesAll Drug Paraphernalia Blood Before 1992 - transfused, products, procedures Sexual Transmission (1-3%) Healthcare Workers – needle sticks Shared House- hold items – razors & toothbrushes Mother to Child <5% Tattoos / Piercing <10% of routes can not be identified www.hcvadvocate.org

11. Transmission & Prevention HCV is not spread by breast feeding, sharing eating utensils or drinking glasses, kissing, hugging Direct blood to blood transmission route www.hcvadvocate.org

12. Transmission & Prevention: Tips Injection and Non-Injection Drugs  Do not share needles, cookers, cottons, straws, pipes or any items that might come into contact with blood  Use bleach to clean People in Stable Long-Term Monogamous Sexual Relationships  CDC – no need to change current sexual practices – but there is a risk www.hcvadvocate.org

13. Transmission & Prevention: Tips Safer Sex  For so called “high risk groups”  Multiple sexual partners, people with sexually transmitted diseases, coinfection with HIV or HBV  Any situation where blood is present www.hcvadvocate.org

14. Transmission & Prevention: Tips Mother to Child Transmission  Low risk – about 5-6%  Given the low rate of transmission, pregnancy should not be avoided.  Note: pregnant women can not take interferon or ribavirin Health-Care Settings  Follow standard/universal precautions www.hcvadvocate.org

15. Transmission & Prevention: Tips Tattoos & Piercing  Considered a low risk in commercial setting  Make sure disposable needles and separate ink pots are used and that general safety precautions are followed  Considered a higher risk in other settings  Non-commercial settings such as in prison or on the streets www.hcvadvocate.org

16. Household  Cover cuts or sores  Do not share personal hygiene items (toothbrushes, razors, etc.) Professional Personal Care Settings  Standard precautions  Disposable equipment  Bring own equipment www.hcvadvocate.org HCV Transmission & Prevention: Tips

17. Chronic Symptoms Fatigue – mild to severe Flu-like symptoms (muscle/joint/fever) ‘Brain Fog’ Liver pain Loss of appetite Headaches Gastro problems and more…… www.hcvadvocate.org

18. HCV Disease Progression 10-25% of HCV positive people progress on to serious disease over 10-40 years  Fibrosis  Light scarring  Cirrhosis  Compensated vs. decompensated  Steatosis  Fatty deposits in the liver www.hcvadvocate.org

19. Disease Progression: Managing Hepatitis C Regular medical monitoring Get vaccinated – Hep A & Hep B Healthy balanced di et www.mypyramid.gov www.mypyramid.gov Exercise Stress Reduction Support Groups Alcohol – Avoid or reduce www.hcvadvocate.org

20. HCV Treatment What is interferon?  General antiviral – immune booster  By injection What is ribavirin?  Antiviral Used only in combination with interferon Pill or capsule www.hcvadvocate.org

21. Treatment - Standard of Care Merck/Schering – PEG-Intron + Rebetol (800mg)  Genotype 1- 41% SVR (48 weeks)  Genotypes 2 thru 6 – 75% (48 weeks) Genentech/Roche – Pegasys + Copegus (1000-1200 mg)  Genotype 1 – 44-51% SVR (48 weeks)  Genotypes 2 & 3 – 82% SVR (24 weeks)  Genotypes 2 thru 6 – 70% SVR (48 weeks) * FDA Package Insert www.hcvadvocate.org

22. Side-effects Interferon  Fatigue  Muscle/Joint pain  Nausea  Headaches  Anxiety  Depression  Dry Skin/Rashes  And more….. Ribavirin  seems to make interferon side effects worse – especially fatigue – Anemia **(both men & women must use birth control) www.hcvadvocate.org

23. Managing Side-Effects Inject before bedtime Drink lots of water Low doses of ibuprofen or acetaminophen Pain medications Small frequent meals Light exercise Daily moisturizing Vary injection sites Anti-Depressants Plenty of rest Key: support from medical providers, family, friends, work – all areas of life www.hcvadvocate.org

24. Complementary Medicine Herbs – milk thistle, licorice root, etc.  Always check with your doctor and herbalist – some herbs are unsafe Acupuncture / Acupressure Traditional Chinese Medicine www.hcvadvocate.org

25. HIV HCV Single stranded RNA Retrovirus Integrates into DNA Single stranded RNA Flavivirus Does not integrate into DNA Comparisons www.hcvadvocate.org

26. HIV HCV Mainly infects CD 4 cells Daily – replicates billions High mutation rate Mainly infects liver cells Daily – replicates trillions Very high mutation rate Comparisons www.hcvadvocate.org

27. HIV HCV Chronic – 100% US – 1 major strain High sexual transmission rate High IDU transmission rates (Blood) Chronic rates - 55-85% US – 3 major strains Low Sexual transmission rate Very high IDU transmission rates (Blood) Comparisons www.hcvadvocate.org

28. HIV HCV Cure?  No Treatment - lifelong Can become resistant Cure?  Virological Cure Treatment 24 to 48 weeks No resistant issues yet  New direct antivirals will lead to resistance Comparisons – Con’t www.hcvadvocate.org

29. HIV HCV U.S. – ~1,000,000 U.S. – ~4,000,000 Comparisons – Prevalence www.hcvadvocate.org

30. Guidelines for Prevention of Opportunistic Infections HIV – Infected persons should be screened for HCV Patients should be advised on alcohol use Patients should be screened for HAV & HBV if negative, they should be vaccinated Patients should be evaluated for liver disease and possible need for treatment Liver enzymes should be monitored after initiation of HAART *U.S. Public Health Service and the Infectious Disease Society of America www.hcvadvocate.org

31. Transmission / Prevention Diagnosing HCV HCV Disease Progression HCV Treatment Response Hepatitis C vs. HIV/HCV Coinfection www.hcvadvocate.org

32. HCV HIV/HCV Coinfection Sexual transmission is low (0-3%) Mother-to-Child Transmission ~5-6%  HCV meds can cause birth defects Sexual transmission is higher ~ 15-25% Mother-to-Child Transmission ~25%  HCV meds can cause birth defects HCV Transmission www.hcvadvocate.org

33. Hepatitis C HIV/HCV Coinfection Antibody Test HCV Viral load to confirm active infection Antibody Test  Note: If low cd4 cell count use HCV RNA HCV RNA to confirm active infection Diagnosing HCV www.hcvadvocate.org *People with a comprised immune system may not develop HCV antibodies

34. Hepatitis C HIV/HCV Coinfection Slow rate of disease progression – usually over 10, 20, 30 years Faster rate of disease progression to cirrhosis – up to 2-3 times faster & can occur in as little as 10 years HCV coinfection is the leading cause of death among people with HIV HCV Disease Progression www.hcvadvocate.org

35. Does HCV Make HIV Worse? Still a controversial issue but most experts do not believe that HCV makes HIV worse  HCV may blunt immune reconstitution www.hcvadvocate.org

36. Does HIV Make HCV Worse? HIV accelerates HCV disease progression – doubles the risk for cirrhosis and increases the chance for liver cancer Some evidence suggests that when HIV is stable – HCV disease progression is slowed in people with HIV/HCV coinfection www.hcvadvocate.org

37. When and Which to Treat? Generally, HIV should be under control  Most recommend treat HIV first HCV – People with HIV/HCV should be considered for HCV treatment  Unless:  CD4 counts less than 200  Active opportunistic illness www.hcvadvocate.org

38. HIV Meds and the Liver Generally, some medications including HIV medications can be difficult for a liver to process HIV meds temporarily increase liver enzymes and HCV viral load – usually stabilize over time  If ALT’s 4 to 5 times baseline –  Change to more liver friendly HIV medications www.hcvadvocate.org

39. Recommendations HIV specialist and liver specialist should closely follow co-infected people Monitor liver functions especially when on HIV treatment Switch to more liver friendly HIV medications www.hcvadvocate.org

40. HCV Treatments Treatment response rates lower in people with HIV  Genotype 1 up to 29%; Genotype 2,3 up to 62% Closely monitored for:  Anemia rates up to 50% caused by ribavirin  Thrombocytopenia (low platelets) caused by interferon  Neutropenia (low white blood cells) caused by interferon www.hcvadvocate.org

41. Ribavirin and HIV Medications Ribavirin originally developed for HIV, but not effective HIV medications that should be avoided or used with caution when combined with ribavirin:  D4T (Zerit)  AZT (Retrovir)  DDI (Videx) www.hcvadvocate.org

42. Psychological Impact Two or more potentially life-threatening conditions Lack of awareness Lack of support www.hcvadvocate.org

43. HCV ORAQUICK RAPID HCV ANTIBODY TEST Venous – whole blood only – clinics $20.00 ? Available some time in 2010 Results in 20 minutes Finger prick and oral swab Filing for marketing approval likely by end of 2010 Approval expected in 2011 Advances in HCV: Diagnostic Tools www.hcvadvocate.org

44. THE BIOSENSOR - HANDHELD Detect infections – HIV, Hepatitis, HINI, STI, Anthrax Tests blood, saliva, urine – the fluid is injected into a small hole in the device Runs on AA batteries - results in 5 seconds Developed by University of New Mexico and Sandia National Laboratories Estimated cost - $5,000 device - $10.00 for chips – 2 years away? Advances in HCV: Diagnostic Tools www.hcvadvocate.org

45. IL28B A variation in IL28B called CC genotype = 2-fold increase in response ~80% of those who achieved response (SVR) had CC genotype Partly explained SVR differences in African Americans and Hispanics Test commercially available in August 2010? Advances in HCV: Treatment www.hcvadvocate.org

46. HCV PROTEASE INHIBITORS Telaprevir and boceprevir - genotype 1 - in combination with pegylated interferon and ribavirin Increase efficacy by 10 to 30% Treatment duration - response guided therapy Telaprevir – skin rash – may be whole body rash Boceprevir – higher rates of anemia Advances in HCV : Treatment www.hcvadvocate.org

47. MEDICATION BURDEN: Telaprevir – every 8 hours Pegylated interferon (sq) once-a-week Ribavirin – taken twice a day Adherence Resistance Advances in HCV: Treatment www.hcvadvocate.org

48. SOME UNANSWERED QUESTIONS – ARE ALL ORAL MEDICATIONS VIABLE? PROBABLY A COMBINATION OF DIFFERENT HCV PROTEASE AND POLYMERASE INHIBITORS AT LEAST 5 TO 10 YEARS AWAY Advances in HCV: Oral Meds Only www.hcvadvocate.org

49. THANKS! The End www.hcvadvocate.org