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

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Population

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mb

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infe

cted

(m

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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

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Population

Perc

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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

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(ME

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HIV positive (n=122)Matched controls (n=122)

4

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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

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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.

robertcaldwell@icloud.com