1 Hepatitis C Overview Patricia Perkins, MS, MPH Tri City Institute: LA, CA

1 HIV/HCV Co-Infecion “Today if you are not confused, you are just not thinking clearly” » HIV Researcher – NYC

1 The Liver Largest internal organ Approximately 3 lbs (men) Size of a football 1.5 quarts of blood flow through it every minute

1 Liver Functions Bile Immune System Chemical Factory- >500 chemical functions Detoxifies Clotting Factors Hormones Regenerates Itself!

1 Keep Your Liver Healthy (Healthy People) No more than: 2 alcoholic drinks daily for men 1 alcoholic drink daily for women Be cautious about mixing drugs – especially with alcohol Healthy, balanced diet Get HAV & HBV vaccinations Avoid toxic substances / fumes

1 Some Statistics 3% of world has HCV ( million) 3.9 Million in U.S. infected with HCV * Chronic – 2.7 Million in U.S. 8,000 to 10,000 in U.S. die of complications from HCV – in 10 years this # will triple HCV is the leading cause for liver transplants 50-80% of HCV infected become chronic * Does not include prisoners, homeless

1 More Statistics U.S. Population 1.8% overall 2.1% Mexican- Americans 3.4 African Americans California 500,000 infected with HCV 85-95% - IDU’s Prisons – 63,500 inmates infected or (41%)

1 What Does It Mean? Only 10-25% progress on to serious liver disease Treatment choices do work for some Hopefully better treatment options will be available within 5 years Lifestyle changes can make a big difference

1 Diagnostic Tools Elisa II / Riba – Test for anti-body Hepatitis C RNA by PCR - >50 particles Hep C RNA by branched DNA Assay – >200,000 particles TMA – more sensitive, less expensive Genotype (six major subtypes – 72% of U.S. population have genotype 1) Liver Biopsy

1 Transmission / Prevention <10% of routes cannot be identified Tattoos / Piercing Neonatal – <5% Shared House- hold items – razors & toothbrushes Healthcare workers – needle sticks Sexual Transmission (1-3%) Blood before transfused, products, procedures All Drug Paraphernalia Shared Needles

1 Harm Reduction Prevention – Needle exchange – clean needles and drug preparation tools – cookers & cottons Bleach – Does it work? 10 minutes! Safer Sex Cover wounds

1 HCV CAN NOT BE SPREAD BY: BREAST FEEDING SNEEZING HUGGING COUGHING FOOD OR WATER SHARING EATING UTENSILS OR DRINKING GLASSES CASUAL CONTACT

1 Symptoms Acute vs. Chronic Fatigue – mild to severe Flu-like symptoms (muscle/joint/fever) ‘Brain Fog’ Liver Pain Loss of appetite Headaches Gastro Problems

1 Treatment Medications Interferon – by injection - first FDA approved treatment (3 MU, thrice weekly for 48 weeks) Genotype 1 - 9% SVR Genotype other than 1 –30% SVR

1 Interferon and Ribavirin Interferon and ribavirin(capsule)- ‘combo therapy’ INF – 3 mu units, thrice weekly - Ribavirin mg daily Overall SVR up to 45% Genotype 1 – 12 mos – 29% SVR Genotype Non 1 – 6 mos - 62% SVR

1 Pegylated Interferon Schering- PEG-Intron Approved by FDA – % sustained response rate Genotype 1 – 14% Genotype 2 & 3 – 47% ROCHE – Pegasys – FDA approval pending 39% sustained response rate Genotype – 1 – 28% Genotype – 2 & 3 – 56%

1 Pegylated and Ribavirin Schering – PEG-Intron plus ribavirin Phase III clinical data – 54% sustained response rates One group improved SVR - Genotype 1 low viral load FDA Approved Roche – Pegasys plus ribavirin Phase III clinical data – 56% sustained response rate – Genotype 1 – 46% - Genotype 2-3, 76% Pending FDA Approval

1 Treatment Decisions General Treatment Guidelines Healthy Active HCV Elevated ALT’s Compensated liver disease Optimal Response Younger Female Low visceral fat Low viral load Minimal liver damage Genotype 2 or 3

1 Side-effects Interferon Fatigue Muscle/Joint pain Nausea Headaches Anxiety Depression Dry Skin/rashes Ribavirin seems to make interferon side effects worse – especially fatigue-Anemia (both men & women must use birth control)

1 Managing Side-Effects Inject before bedtime Drink lots of water Low doses of ibuprofen or acetaminophen Pain medications Light exercise Daily moisturizing Vary injection sites Anti-Depressants Plenty of rest Frequent small meals

1 Experimental Therapies Amantadine - pill Maxamine – by injection (phase II studies) Ribozymes Helicase Inhibitors Protease Inhibitors Interleukin-10

1 Complementary Medicine Herbs – milk thistle Always check with your doctor and herbalist – some herbs are TOXIC Acupuncture / Acupressure Traditional Chinese Medicine

1 Lifestyle Changes That Help! Alcohol - Avoid Get vaccinated – Hep A & Hep B Healthy balanced diet Exercise Stress Reduction Support Groups

1 Advocate for Yourself and Your Client! Educate yourself Establish a good relationship with your doctor Bring an advocate for doctor’s visits Ask questions Keep copies of all medical tests Keep a diary Keep an open mind

1 Comparisons – HIV & HCV HIV Single stranded RNA Retrovirus Mainly infects CD4 cells Daily-replicates millions HCV Single stranded RNA Flavivirus Mainly infects liver cells Daily – replicates in trillions

1 Comparisons HIV/HCV, cont. HIV is: Chronic = 100% US-1 major strain High sexual transmission rate High IDU transmission (blood) HCV is: Chronic – 60-85% US-3 major strains Low sexual transmission rates Very high IDU transmission rates (blood to blood)

1 HIV/HCV Comparisons, cont. HIV Curable? Can become resistant to antiviral drugs HCV Curable? Does not become resistant to current drugs

1 HIV/HCV Co-Infection Statistics: US HIV Infections = 750,000 Up to 40% of people with HIV also infected with HCV = 300,000 Worldwide HIV infections = 170 million Estimated 23-75% of people with HIV also infected with HCV = 8-27 million

1 Guidelines for Prevention of Opportunistic Infections* HIV – All should be screened for HCV Patients should be counseled on alcohol use Patients should be screened for HAV – if negative, should be vaccinated; Hep B, triage based on risk & expense Patients should be evaluated for liver disease and possible need for treatment Liver enzymes should be monitored after initiation of HAART *US PHS (CDC) & IDSA

1 HIV Medications Known to Be Hard on the Liver Documented potential liver toxicities: Ritonavir (Norvir) Crixivan (Indinavir) Viramune (Nevirapine) Sustiva (Efavirenz) Kaletra (Lopinavir)

1 Recommendations HIV specialist and liver specialist should jointly monitor co-infected patients Monitor liver functions especially when on treatment for HIV Switch medications to less liver toxic

1 Interferon and HIV History: Interferon unsuccessfully used to treat HIV – during and pre-AZT Approved for use in Kaposi's Sarcoma Currently looking at INF again Why? High INF levels accelerate HIV progression (Gallo et al at NIH) INF harms immune system in HIV+?

1 HCV Transmission for HIV+ Higher risk of transmitting sexually – may be due to higher viral load burden among co-infected – unclear Mother to child – vertical transmission up to 25% risk during delivery

1 Diagnosis HIV ELISA Western blot for confirmation HCV ELISA II (RIBA to confirm – not rec'd) Viral load – test for active HCV disease (small percentage of people with HIV/HCV do not develop antibodies to HCV)

1 Does HCV Make HIV Worse? Still controversial but most experts do NOT believe that HCV makes HIV worse Exception – hemophiliacs (high viral burden)

1 Does HIV Make HCV Worse? Most experts believe that HIV accelerates HCV disease progression Some data suggest that when HIV is stable – low viral load, higher CD4 – HCV disease progression is slowed in co- infected persons

1 When & Which to Treat? Generally, HIV should be under control Treat HIV first – with HAART HCV – People with HIV/HCV should be considered for HCV treatment Exceptions: CD4 counts <200 Active opportunistic infection

1 HIV Medications & the Liver In general, ALL medications can be hard on the liver HIV meds temporarily increase liver enzymes (ALT) & HCV viral load – usually levels out in 3-6 mos. If ALTs 4-5x baseline -- Change or discontinue medicine

1 Ribavirin & the Liver Ribavirin originally developed for HIV – not effective Anemia - ribavirin & AZT both cause anemia – AVOID together Ribavirin decreases AZT and to a lesser extent D4T (Zerit TM) ) in vitro (test-tube) Ribavirin may make DDI work better

1 HCV Treatments Similar response rates to HCV mono- infected Closely monitor patients for: Anemia – up to 50% of co-infected (rbv) Thrombocytopenia - low platelets (inf) Neutropenia – low white blood cells (inf)

1 Psychological Impact of Co-Infection Two life-threatening diseases Lack of awareness/denial among patients and existing HIV support systems Lack of support among traditional HIV support systems/groups

1 Conclusions Hepatitis C is a manageable chronic illness; misunderstandings/stigma persist Lifestyle changes can enhance treatment outcomes & side effects Management of HIV/HCV co-infection is possible, do-able, and difficult Misunderstandings/stigma & lack of support exist for drug users co-infected