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.1 2 3 4 5
Population
Number infected (millions)
HCV
HIV
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
Nearly 4 million persons in the United States are infected with hepatitis C virus (HCV). Approximately 35,000 new cases are diagnosed each year.
Approximately 35,000 new cases yearly
Fallen from 230,00/yr in 80s
Liver transplantation
A major issue is that most cases—approximately 85%—become chronic resulting in hepatitis C accounting for the leading cause of chronic liver disease, cirrhosis, and liver cancer in the United States, as well as the number one indication for liver transplantation.
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
Shared Needles
All Drug Paraphernalia
Blood Before 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

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

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

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

14. 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
NOT ASSOCIATED:
HCV “VIRAL LOAD”
HCV GENOTYPE
SERUM ALT
? SMOKING

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

20. Comparisons HIV HCV MAINLY INFECTS LIVER CELLS
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

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

22. Comparisons HCV HIV Cure? Cure? Treatment - lifelong
Virological Cure
Treatment 24 to 48 weeks
No resistant issues yet
New direct antivirals will lead to resistance
Cure? No
Treatment - lifelong
Can become resistant

23. HCV Transmission HIV/HCV Co-Infection HCV
SEXUAL TRANSMISSION IS HIGHER (~ 15-25%)
MOTHER-TO-CHILD TRANSMISSION ~25%
HCV MEDS CAN CAUSE BIRTH DEFECTS
SEXUAL TRANSMISSION IS (0-3%)
MOTHER-TO-CHILD TRANSMISSION ~5-6%
HCV MEDS CAN CAUSE BIRTH DEFECTS

24. Diagnosing HCV HIV/HCV CO-INFECTION Hepatitis C 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
*People with a comprised immune system may not develop HCV antibodies

25. HCV may blunt immune system reconstitution.
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 Subjects20 40 60 80
100
Population
Percentage
IVDU
90%
MSM10%
All HIV+
33%
US Pop.
1.9%
180 MILLION People worldwide. Prevalnce 1.6% 4 million people have been infected with HCV, and 10,000 HCV-related deaths occur each year. 80% viremic. Leading cause of death from liver dx, leading cause of liver transplantation.
17,000 ACUTE CASES YEARLY BUT UNDER REPORTED.
Sulkowski MS, et al. Clin Infect Dis. 2000;30:

28. HCV Disease Progression
HIV/HCV Co-Infection
Hepatitis C
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
SLOW RATE OF DISEASE PROGRESSION – USUALLY OVER 10, 20, 30 YEARS

29. HIV Co-Infection Accelerates Liver Fibrosis Progression Rate
(METAVR scoring system)
Fibrosis Grades
HIV positive (n=122)
Matched controls (n=122) 4 3 2 1 10 20 30 40
About 2 fold increase risk of cirrhosis.
Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection.
In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate
Prev of extensive fibrosis and mod to severe activity were 60, 54% to 47, 30% respectively.
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
Higher number of cases of acute rejection
50% occur in ≤ first 21 days
P=0.01
P=0.01
HCV mono-infected N= N= N=22
HCV-HIV co-infected N= N= 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. TWO OR MORE POTENTIALLY LIFE- THREATENING CONDITIONS
Psychological Impact
TWO OR MORE POTENTIALLY LIFE- THREATENING CONDITIONS
LACK OF AWARENESS
LACK OF SUPPORT
FINANCIAL BURDENS

36. WASHINGTON HOSPITAL CENTER, MEDSTAR HEALTH
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.