ADAP ADVOCACY ASSOCIATION2013 HIV/HCV CO-INFECTION ADAP SUMMIT
ROBERT L. CALDWELL, PH.D.
A MEDICAL PERSPECTIVE ON HIV/HCV CO-INFECTION
HIV and Hepatitis C Co-Infection
GENERAL OVERVIEW OF HEPATITIS C
HIV AND HEPATITIS C – DIFFERENCES AND SIMILARITIES
HIV AND HEPATITIS C CO-INFECTION
TREATMENT OF THE CO-INFECTED PATIENT
Agenda
HCV STATISTICS
THE HCV DIAGNOSIS
HCV TRANSMISSION & PREVENTION
HCV SYMPTOMS, DISEASE PROGRESSION, MANAGEMENT
Hepatitis C Overview
U.S. POPULATION
(1.6% OVERALL)
~4 MILLION AMERICANS INFECTED
3.2 MILLION CHRONICALLY INFECTED
Hepatitis C Statistics
Hepatitis C Is A Common Public Health Problem In The U.S.
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
0
1
2
3
4
5
Population
Nu
mb
er
infe
cted
(m
illi
on
s)
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
HCV ELISA IMMUNOASSAY (EIA)
MOST COMMON ANTIBODY TEST
POSITIVE ANTIBODY TEST INDICATES EXPOSURE
DOES NOT INDICATE ACTIVE HEPATITIS C INFECTION
HCV Diagnostics: Antibody Tests
GOLD STANDARD FOR DETERMINING THE HEALTH OF THE LIVER
MEASURE OF INFLAMMATION
EXTENT OF SCARRING (IF ANY)
NON-INVASIVE METHODS – NOT AS ACCURATE
HCV Diagnostics: Liver Biopsy
Transmission and Prevention
Shared Needles All Drug ParaphernaliaBlood 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
HCV IS NOT SPREAD BY BREAST FEEDING, SHARING EATING UTENSILS OR DRINKING GLASSES, KISSING, HUGGING
DIRECT BLOOD TO BLOOD TRANSMISSION ROUTE
Transmission and Prevention
HCV Infection Demographics HCV Infection Demographics (US)(US)
General General PopulationPopulation
1.6%1.6%White: 1.5%White: 1.5%
African American: 3%African American: 3%African American Males, African American Males, 50-59 years of age: 13.6%50-59 years of age: 13.6%
Veterans(esp. Vietnam) : ~20%Veterans(esp. Vietnam) : ~20%HIV + people: 25-30%HIV + people: 25-30%
Homeless people: ~40%Homeless people: ~40%Current & former IDU: up to 90%Current & former IDU: up to 90%
Chronic HCV Symptoms
LIVER PAIN
LOSS OF APPETITE
HEADACHES
GASTRO PROBLEMS
FATIGUE – MILD TO SEVERE
FLU-LIKE SYMPTOMS (MUSCLE/JOINT/FEVER)
‘BRAIN FOG’
10-25% OF HCV POSITIVE PEOPLE PROGRESS TO SERIOUS LIVER DAMAGE OVER 10-40 YEARS
FIBROSISLIGHT SCARRING
CIRRHOSISCOMPENSATED VS. DECOMPENSATED
STEATOSISFATTY DEPOSITS IN THE LIVER
HCV Disease Progression
WHAT IS INTERFERON?
GENERAL ANTIVIRAL – IMMUNE BOOSTERBY INJECTION
WHAT IS RIBAVIRIN?
ANTIVIRAL USED ONLY IN COMBINATION WITH INTERFERONPILL OR CAPSULE
HCV Treatment
AGE > 50 YEARSDURATION OF INFECTIONMALE GENDERIRON OVERLOADSTEATOSISALCOHOLCO-INFECTION WITH HIV
Factors Associated with Disease Progression in HCV Infected
Patients
NOT ASSOCIATED:
HCV “VIRAL LOAD”HCV GENOTYPESERUM ALT? SMOKING
HIV ~1,000,000
HCV ~4,000,000
HIV ~1,000,000
HCV ~4,000,000
Comparisons – Prevalence in the United States
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
VIROLOGICAL COMPARISONS
TRANSMISSION AND DIAGNOSIS
CO-INFECTION STATISTICS
DISEASE PROGRESSION
TREATMENT RESPONSE
Hepatitis C and HIV/HCV Co-Infection
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.
HIVHIV
Comparisons
HCVHCV
SINGLE STRANDED RNA
RETROVIRUS
INTEGRATES INTO DNA
SINGLE STRANDED RNA
FLAVIVIRUS
DOES NOT INTEGRATE INTO
DNA
HIVHIV
Comparisons
HCV HCV
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 HIV
Comparisons
www.hcvadvocate.org
HCV HCV
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)
HIVHIV
Comparisons
HCVHCV
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
HCVHCV
HCV Transmission
HIV/HCV Co-Infection HIV/HCV Co-Infection
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
HEPATITIS C HEPATITIS C
Diagnosing HCV
HIV/HCV CO-INFECTION HIV/HCV CO-INFECTION
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
STILL A CONTROVERSIAL ISSUE BUT MOST EXPERTS DO NOT BELIEVE THAT HCV MAKES
HIV WORSE
HCV may blunt immune system reconstitution.
Does HCV Make HIV 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.
Does HIV Make HCV Worse?
HCV Co-Infection is Common in HIV Infected Subjects
0
20
40
60
80
100
Population
Perc
en
tag
e
IVDU90%
MSM10%
All HIV+33%
US Pop.1.9%
Sulkowski MS, et al. Clin Infect Dis. 2000;30:
HEPATITIS C HEPATITIS C
HCV Disease Progression
HIV/HCV Co-InfectionHIV/HCV Co-Infection
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
HIV Co-Infection Accelerates Liver Fibrosis Progression Rate
HCV - infection duration (years)
0
Fib
rosi
s G
rad
es
(ME
TA
VR
scori
ng
sys
tem
)
HIV positive (n=122)Matched controls (n=122)
4
3
2
1
010 20 30 40
Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010
Patient Survival Post Liver Transplant: Mono- vs. C0-
Infection
P=0.01P=0.01
HCV mono-infected N=135 N=67 N=22
HCV-HIV co-infected N=46 N=28 N=14
% P
ATIE
NT S
UR
VIV
AL
0
20
40
60
80
100
YEAR0.0 0.5 1.0 1.5 2.0 2.5 3.0
HCV-HIV CoinfectedHCV Monoinfected
P=0.01
Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010
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.
Why Treat HIV/HCV Co-Infected Patients?
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
When and Which to Treat?
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.
HIV Meds and the Liver
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
Recommendations
TWO OR MORE POTENTIALLY LIFE-THREATENING CONDITIONS
LACK OF AWARENESS
LACK OF SUPPORT
FINANCIAL BURDENS
Psychological Impact
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
Acknowledgements
Contact Information:Robert L. Caldwell, Ph.D.
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