Transcript Hepatitis C and HIV/HCV Coinfection

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 COINFECTION
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
Hepatitis C Overview
HCV STATISTICS
THE HCV DIAGNOSIS
HCV TRANSMISSION & PREVENTION
HCV SYMPTOMS, DISEASE PROGRESSION,
MANAGEMENT
Hepatitis C Statistics
U.S. POPULATION
(1.6% OVERALL)
~4 MILLION AMERICANS INFECTED
3.2 MILLION CHRONICALLY INFECTED
Hepatitis C Is A Common Public
Health Problem In The U.S.
Number infected (millions)
5
HCV
DEATHS: 8,000 – 15,000/YEAR
- 56% INCREASE IN HCV ASSOCIATED
MORTALITY (1999 – 2007)
4
3
HCV IS THE LEADING CAUSE OF
 CHRONIC LIVER DISEASE
2
 CIRRHOSIS
HIV
1
 LIVER CANCER : 50% OF CASES
(HCC FASTEST RISING CAUSE OF
CANCER-RELATED DEATH)
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
LIVER TRANSPLANTATION
HCV Diagnostics: Antibody
Tests
HCV ELISA IMMUNOASSAY (EIA)
MOST COMMON ANTIBODY TEST
POSITIVE ANTIBODY TEST INDICATES EXPOSURE
DOES NOT INDICATE ACTIVE HEPATITIS C INFECTION
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
Transmission and Prevention
Shared Needles
All 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
Transmission and Prevention
HCV IS NOT SPREAD BY BREAST FEEDING,
SHARING EATING UTENSILS OR DRINKING
GLASSES, KISSING, HUGGING
DIRECT BLOOD TO BLOOD TRANSMISSION
ROUTE
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%
Chronic HCV Symptoms

LIVER PAIN

FATIGUE – MILD TO SEVERE

LOSS OF APPETITE

FLU-LIKE SYMPTOMS
(MUSCLE/JOINT/FEVER)

HEADACHES

‘BRAIN FOG’

GASTRO PROBLEMS
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
HCV Treatment
WHAT IS INTERFERON?
GENERAL ANTIVIRAL – IMMUNE BOOSTER
BY INJECTION
WHAT IS RIBAVIRIN?
ANTIVIRAL
USED ONLY IN COMBINATION WITH INTERFERON
PILL OR CAPSULE
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
Comparisons – Prevalence in the
United States
HIV ~1,000,000
HCV ~4,000,000
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
Hepatitis C and HIV/HCV CoInfection
VIROLOGICAL COMPARISONS
TRANSMISSION AND DIAGNOSIS
CO-INFECTION STATISTICS
DISEASE PROGRESSION
TREATMENT RESPONSE
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 5090% AMONG CERTAIN SUB-POPULATIONS.
SUPPORTING EVIDENCE THAT HIV NEGATIVELY IMPACTS
HCV DISEASE PROGRESSION AND REDUCES THE
EFFECTIVENESS OF AVAILABLE TREATMENTS.
Comparisons
HIV
HCV

SINGLE STRANDED RNA

SINGLE STRANDED RNA

RETROVIRUS

FLAVIVIRUS

INTEGRATES INTO DNA

DOES NOT INTEGRATE INTO DNA
Comparisons
HIV
HCV

MAINLY INFECTS LIVER CELLS
CELLS

DAILY – REPLICATES TRILLIONS

DAILY – REPLICATES BILLIONS

VERY HIGH MUTATION RATE

HIGH MUTATION RATE

MAINLY INFECTS CD 4+ CELLS,
MACROPHAGES AND DENDRITIC
Comparisons
HCV
HIV

CHRONIC – 100%

CHRONIC RATES - 55-85%

US – 1 MAJOR STRAIN

US – 3 MAJOR STRAINS

HIGH SEXUAL TRANSMISSION
RATE

VERY HIGH SEXUAL
TRANSMISSION RATE

HIGH IDU TRANSMISSION RATES
(BLOOD)

VERY HIGH IDU TRANSMISSION
RATES (BLOOD)
www.hcvadvocate.org
Comparisons
HCV
HIV
 Cure?

No
 Cure?

Virological Cure
 Treatment - lifelong
 Treatment 24 to 48 weeks
 Can become resistant
 No resistant issues yet

New direct antivirals will lead to
resistance
HCV Transmission
HIV/HCV Co-Infection
HCV
 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
Diagnosing HCV
HIV/HCV CO-INFECTION
HEPATITIS C

ANTIBODY TEST

ANTIBODY TEST
 NOTE: IF LOW CD4+ CELL
COUNT, MEASURE HCV RNA

HCV VIRAL LOAD TO CONFIRM
ACTIVE INFECTION

HCV RNA TO CONFIRM ACTIVE
INFECTION
*PEOPLE WITH A COMPRISED IMMUNE SYSTEM MAY NOT DEVELOP HCV
ANTIBODIES
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.
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.
HCV Co-Infection is Common in HIV
Infected Subjects
100
IVDU
90%
Percentage
8
0
6
0
All
HIV+
33%
4
0
2
0
MSM
10%
0
Population
Sulkowski MS, et al. Clin Infect Dis. 2000;30:
US Pop.
1.9%
HCV Disease Progression
HEPATITIS C
 SLOW RATE OF DISEASE
PROGRESSION – USUALLY
OVER 10, 20, 30 YEARS
HIV/HCV Co-Infection
 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
Fibrosis Grades
(METAVR scoring system)
HIV Co-Infection Accelerates Liver
Fibrosis Progression Rate
4
3
2
HIV positive (n=122)
Matched controls (n=122)
1
00
10
20
30
HCV - infection duration (years)
Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010
40
Patient Survival Post Liver
Transplant: Mono- vs. C0-Infection
100
% PATIENT SURVIVAL
80
60
40
P=0.01
P=0.01
20
P=0.01
HCV-HIV Coinfected
HCV Monoinfected
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
YEAR
HCV mono-infected
N=135
N=67
HCV-HIV co-infected
N=46
N=28
Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010
N=22
N=14
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 COINFECTED 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.
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
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.
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
Psychological Impact
TWO OR MORE POTENTIALLY LIFETHREATENING CONDITIONS
LACK OF AWARENESS
LACK OF SUPPORT
FINANCIAL BURDENS
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.
[email protected]