HIV and Hepatitis C Co-Infection ADAP ADVOCACY ASSOCIATION

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 Ann. Int. Med 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 GASTRO PROBLEMS ‘BRAIN FOG’

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 HCV ~4, 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 Co. Infection VIROLOGICAL COMPARISONS TRANSMISSION AND DIAGNOSIS CO-INFECTION STATISTICS DISEASE PROGRESSION TREATMENT RESPONSE

C 0 -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 RETROVIRUS FLAVIVIRUS INTEGRATES INTO DNA DOES NOT INTEGRATE INTO DNA

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

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 HIGH IDU TRANSMISSION RATES (BLOOD) www. hcvadvocate. org RATE VERY HIGH IDU TRANSMISSION RATES (BLOOD)

Comparisons HIV HCV 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 HCV SEXUAL TRANSMISSION IS (0 -3%) MOTHER-TO-CHILD TRANSMISSION ~5 -6% HCV MEDS CAN CAUSE BIRTH DEFECTS HIV/HCV CO-INFECTION SEXUAL TRANSMISSION IS HIGHER (~ 15 -25%) MOTHER-TO-CHILD TRANSMISSION ~25% HCV MEDS CAN CAUSE BIRTH DEFECTS

Diagnosing HCV HEPATITIS C ANTIBODY TEST HIV/HCV CO-INFECTION ANTIBODY TEST HCV VIRAL LOAD TO CONFIRM ACTIVE INFECTION NOTE: IF LOW CD 4+ CELL COUNT, MEASURE 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 80 60 All HIV+ 33% 40 20 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 COINFECTION 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 0 0 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. C 0 -Infection P=0. 01 HCV mono-infected N=135 HCV-HIV co-infected N=46 Terrault et al. HEPATOLOGY 2009 AASLD, Stock P et al: Abstract HIV and Liver Disease 2010 N=67 N=28 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: CD 4+ 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. robertcaldwell@icloud. com