HIV and Hepatitis C Co-Infection

1. HIV and Hepatitis C Co-Infection ADAP ADVOCACY ASSOCIATION 2013 HIV/HCV CO-INFECTION ADAP SUMMIT ROBERT L. CALDWELL, PH.D. A MEDICAL PERSPECTIVE ON HIV/HCV CO-INFECTION

2. Agenda GENERAL OVERVIEW OF HEPATITIS C HIV AND HEPATITIS C – DIFFERENCES AND SIMILARITIES HIV AND HEPATITIS C CO-INFECTION TREATMENT OF THE CO-INFECTED PATIENT

3. Hepatitis C Overview HCV STATISTICS THE HCV DIAGNOSIS HCV TRANSMISSION & PREVENTION HCV SYMPTOMS, DISEASE PROGRESSION, MANAGEMENT

4. Hepatitis C Statistics U.S. POPULATION (1.6% OVERALL) ~4 MILLION AMERICANS INFECTED 3.2 MILLION CHRONICALLY INFECTED

5. Hepatitis C Is A Common Public Health Problem In The U.S. HCV 5 • DEATHS: 8,000 – 15,000/YEAR • - 56% INCREASE IN HCV ASSOCIATED MORTALITY (1999 – 2007) • HCV IS THE LEADING CAUSE OF • CHRONIC LIVER DISEASE • CIRRHOSIS • LIVER CANCER : 50% OF CASES • (HCC FASTEST RISING CAUSE OF CANCER-RELATED DEATH) • LIVER TRANSPLANTATION 4 3 Number infected (millions) 2 1 HIV 0 Population Sulkowski MS et al. Clin Infect Dis. 2000;30 Kim WR et al, Gastro 2009:137; Ly KN et al AnnIntMed 2012: 156; Kanwal F et al Gastro 2011;140

6. HCV Diagnostics: Antibody Tests HCV ELISA IMMUNOASSAY (EIA) MOST COMMON ANTIBODY TEST POSITIVE ANTIBODY TEST INDICATES EXPOSURE DOES NOT INDICATE ACTIVE HEPATITIS C INFECTION

7. 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

8. Transmission and Prevention

9. Transmission and Prevention HCV IS NOT SPREAD BY BREAST FEEDING, SHARING EATING UTENSILS OR DRINKING GLASSES, KISSING, HUGGING DIRECT BLOOD TO BLOOD TRANSMISSION ROUTE

10. HCV Infection Demographics (US) General Population 1.6% White: 1.5% African American: 3% African American Males, 50-59 years of age: 13.6% Veterans(esp. Vietnam) : ~20% HIV + people: 25-30% Homeless people: ~40% Current & former IDU: up to 90%

11. LIVER PAIN LOSS OF APPETITE HEADACHES GASTRO PROBLEMS Chronic HCV Symptoms • FATIGUE – MILD TO SEVERE • FLU-LIKE SYMPTOMS (MUSCLE/JOINT/FEVER) • ‘BRAIN FOG’

12. HCV Disease Progression 10-25% OF HCV POSITIVE PEOPLE PROGRESS TO SERIOUS LIVER DAMAGE OVER 10-40 YEARS FIBROSIS LIGHT SCARRING CIRRHOSIS COMPENSATED VS. DECOMPENSATED STEATOSIS FATTY DEPOSITS IN THE LIVER

13. HCVTreatment WHAT IS INTERFERON? GENERAL ANTIVIRAL – IMMUNE BOOSTER BY INJECTION WHAT IS RIBAVIRIN? ANTIVIRAL USED ONLY IN COMBINATION WITH INTERFERON PILL OR CAPSULE

14. NOT ASSOCIATED: HCV “VIRAL LOAD” HCV GENOTYPE SERUM ALT ? SMOKING Factors Associated with Disease Progression in HCV Infected Patients AGE > 50 YEARS DURATION OF INFECTION MALE GENDER IRON OVERLOAD STEATOSIS ALCOHOL CO-INFECTION WITH HIV

15. Comparisons – Prevalence in the United States HIV ~1,000,000 HCV ~4,000,000

16. Deaths Associated With Hepatitis C Have Overtaken Deaths Caused By HIV Lk KN et al, Ann of Int Med 2012:156 Holmberg S et al, CDC, AASLD 2011

17. Hepatitis C and HIV/HCV Co-Infection VIROLOGICAL COMPARISONS TRANSMISSION AND DIAGNOSIS CO-INFECTION STATISTICS DISEASE PROGRESSION TREATMENT RESPONSE

18. C0-Infection Statistics IN THE U.S., AN ESTIMATED 1/4 OF THOSE INFECTED WITH HIV ARE ALSO INFECTED WITH HEPATITIS C VIRUS (HCV). ESTIMATES OF HIV/HCV CO-INFECTION RANGE FROM 50-90% AMONG CERTAIN SUB-POPULATIONS. SUPPORTING EVIDENCE THAT HIV NEGATIVELY IMPACTS HCV DISEASE PROGRESSION AND REDUCES THE EFFECTIVENESS OF AVAILABLE TREATMENTS.

19. HCV Comparisons SINGLE STRANDED RNA RETROVIRUS INTEGRATES INTO DNA • Single stranded RNA • Flavivirus • Does not integrate into DNA HIV

20. HCV Comparisons MAINLY INFECTS CD 4+ CELLS, MACROPHAGES AND DENDRITIC CELLS DAILY – REPLICATES BILLIONS HIGH MUTATION RATE MAINLY INFECTS LIVER CELLS DAILY – REPLICATES TRILLIONS VERY HIGH MUTATION RATE HIV

21. HCV Comparisons CHRONIC – 100% US – 1 MAJOR STRAIN HIGH SEXUAL TRANSMISSION RATE HIGH IDU TRANSMISSION RATES (BLOOD) CHRONIC RATES - 55-85% US – 3 MAJOR STRAINS VERY HIGH SEXUAL TRANSMISSION RATE VERY HIGH IDU TRANSMISSION RATES (BLOOD) HIV www.hcvadvocate.org

22. HCV Comparisons • 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 HIV

23. HIV/HCV Co-Infection HCV Transmission • SEXUAL TRANSMISSION IS (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

24. HIV/HCV CO-INFECTION Diagnosing HCV ANTIBODY TEST HCV VIRAL LOAD TO CONFIRM ACTIVE INFECTION • ANTIBODY TEST • NOTE: IF LOW CD4+ CELL COUNT, MEASURE HCV RNA • HCV RNA TO CONFIRM ACTIVE INFECTION Hepatitis C *People with a comprised immune system may not develop HCV antibodies

25. Does HCV Make HIV Worse? STILL A CONTROVERSIAL ISSUE BUT MOST EXPERTS DO NOT BELIEVE THAT HCV MAKES HIV WORSE HCV may blunt immune system reconstitution.

26. Does HIV Make HCV Worse? HIV ACCELERATES HCV DISEASE PROGRESSION, DOUBLING THE RISK FOR CIRRHOSIS AND INCREASES THE CHANCE FOR LIVER CANCER. CLINICAL TRIALS SUGGEST THAT WHEN HIV INFECTION IS CONTROLLED, HCV DISEASE PROGRESSION IS CONTROLLED IN PEOPLE CO-INFECTED.

27. HCV Co-Infection is Common in HIV Infected Subjects IVDU 90% 100 80 60 All HIV+ 33% Percentage 40 MSM10% 20 US Pop. 1.9% 0 Population Sulkowski MS, et al. Clin Infect Dis. 2000;30:

28. HIV/HCV Co-Infection HCV Disease Progression 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 CO-INFECTION IS THE LEADING CAUSE OF DEATH AMONG PEOPLE WITH HIV Hepatitis C

29. HIV Co-Infection Accelerates Liver Fibrosis Progression Rate 4 3 Fibrosis Grades (METAVR scoring system) 2 HIV positive (n=122) Matched controls (n=122) 1 0 30 0 10 20 40 HCV - infection duration (years) Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010

30. Patient Survival Post Liver Transplant: Mono- vs. C0-Infection P=0.01 P=0.01 P=0.01 HCV mono-infected N=135 N=67 N=22 HCV-HIV co-infected N=46 N=28 N=14 Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010

31. Why Treat HIV/HCV Co-Infected Patients? HCV IS COMMON IN HIV PATIENTS (APPROX 25-40% IN U.S.) HCV IS A MORE SERIOUS DISEASE IN CO-INFECTED PATIENTS THAN IN MONOINFECTED. HCV HAS BECOME ONE OF THE LEADING CAUSES OF DEATH IN THE HIV POPULATION. HCV CO-INFECTION CARRIES SIGNIFICANT MORBIDITY, LIMITS ANTI-RETROVIRAL OPTIONS, DECREASES QUALITY OF LIFE.

32. When and Which to Treat? GENERALLY, HIV SHOULD BE UNDER CONTROL TREAT THE HIV INFECTION FIRST. PEOPLE CO-INFECTED SHOULD BE CONSIDERED FOR HCV TREATMENT UNLESS: CD4+ COUNTS LESS THAN 200, AND/OR ACTIVE OPPORTUNISTIC ILLNESS ARE PRESENT

33. 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 AS WELL AS HCV VIRAL LOAD. THESE USUALLY STABILIZE OVER TIME. IF ALT’S 4 TO 5 TIMES BASELINE, THEN CHANGE TO MORE “LIVER-FRIENDLY” HIV MEDICATIONS.

34. 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

35. Psychological Impact TWO OR MORE POTENTIALLY LIFE-THREATENING CONDITIONS LACK OF AWARENESS LACK OF SUPPORT FINANCIAL BURDENS

36. Acknowledgements GREGORY PAPPAS, M.D. HIV/AIDS, HEPATITIS, STD, AND TB ADMINISTRATION, D.C. DEPARTMENT OF HEALTH DAWN FISHBEIN, M.D., M.S. WASHINGTON HOSPITAL CENTER, MEDSTAR HEALTH ROHIT TALWANI, M.D. ASSISTANT PROFESSOR AT UNIVERSITY OF MARYLAND - INSTITUTE OF HUMAN VIROLOGY Contact Information: Robert L. Caldwell, Ph.D. robertcaldwell@icloud.com