1. Hepatitis C: The Next Tsunami Danny Jenkins Cri-Help Common Ground – The Westside HIV Community Center We Write the Grants www.wewritethegrants.com

2. 2 Prevalence and Transmission of HCV and HIV Prevalence 1999 –World: 40-175 million –USA: ~4 million (1.8%) Primary Modes of Transmission –Injection > sexual –Occupational –Perinatal Prevalence 1999 –World: 40 million –USA: ~1 million (0.4%) Primary Modes of Transmission –Sexual > injection –Occupational –Perinatal HCVHIV Lee W, et al. Drugs. 2004;64:693-700.

3. 3 HCV/HIV Coinfected HIV Monoinfected 70% 30% Overall Prevalence of HCV Among HIV-Infected Persons in the United States Thomas D. Hepatology. 2002;36:S201-S209.

4. 4 Hospital Admissions Among HIV-Infected Patients 199519961997199819992000 12 15 8 8 8 8 5 7 8 8 11 22 5 7 8 11 20 32 0 5 10 15 20 25 30 35 Opportunistic infections IDU-related complications Liver-related complications 5-fold increase in liver complications from 1995 to 2000 Hospitalizations Per Patient-Year Follow-Up Gebo K, et al. J Acquir Immune Defic Syndr. 2003;34:165-173.

5. 5 HCV/HIV Coinfected Patients and End-Stage Liver Disease Clinical HCV is accelerated in HIV/HCV coinfection –Faster disease progression with an increased risk of cirrhosis and decompensated liver disease –More patients develop cirrhosis within given timeframe –Alcohol has an additional aggravating effect 1.Graham C, et al. Clin Infect Dis. 2001;33:562-569. 2.Lee W, et al. Drugs. 2004;64:693-700.

6. 6 HCV/HIV Coinfection: An Area of High Medical Need One third of HIV patients are coinfected with HCV 1 –Among HIV-infected IDU, this rises to 50%-90% 2 HCV viral load higher in HCV/HIV vs. HCV patients 3 HIV accelerates clinical course of HCV-related liver disease –Time to cirrhosis significantly reduced 4 –Liver disease is now the leading cause of death in hospitalized AIDS patients 5 HCV may also impact the course of HIV disease 1. Thomas D. Hepatology. 2002;36:S201-S209. 2.Sulkowski M, et al. Ann Intern Med. 2003;138:197-207. 3. Soriano V, et al. J Hep. 2006:44;S44-S48. 4. Soto B, et al. J Hep. 1997:26;1-5. 5. Bica I, et al. Clin Infect Dis. 2001;32:492-497. 6. Sulkowski M, et al. Hepatology. 2002;35:182-189. 7. Greub G, et al. Lancet. 2000;356:1800-1805.

7. 7 Hepatitis C (HCV) Basics Blood-borne virus (formerly non-A/non-B hepatitis) Six major genotypes: 1a, 1b, 2a, 2b, 3, 4, 5 & 6 1a and 1b = most common in US & difficult to treat

8. 8 Hepatitis C (HCV) Basics Enters body through direct blood exposure Attacks liver -> multiples (replicates) Causes liver inflammation and kills liver cells

9. 9 Natural History of HCV Infection Exposure (Acute phase) ResolvedChronic Cirrhosis Stable SlowlyProgressive Liver Cancer TransplantDeath 20% 15%85% 25% 80% 75% HIV Alter MJ. Semin Liver Dis. 1995;15:5-14. Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3). Alcohol 2-12 Wks 10-40 Yrs

10. 10 Transmission Blood to bloodstream Syringes, cookers, tattooing, piercing, razors, toothbrushes Sexual transmission (very) rare Perinatal 5%

11. 11 Typical Symptoms Nausea Fatigue Fever Headaches Loss of appetite Abdominal pain Muscle/joint pain Flu-like symptoms Jaundice Dark urine

12. 12 Some HCV Numbers Likely that >4M Americans infected 8-10K Americans die annually This is expected to triple in 10-20 years Alcohol & drugs are like HCV fuel Hepatitis A & B Vaccines are a must

13. 13 Factors Associated with Disease Progression in HCV Infected Patients Age > 50 years Duration of infection Male gender Iron overload Steatosis Alcohol Co-infection with HBV Co-infection with HIV Not associated: HCV “viral load” HCV genotype Serum ALT ? Smoking

14. 14 HCV Tests Antibody tests: Elisa & RIBA Viral Load  Predict Medical TX Response  Measure Rx Effectiveness  NOT to measure disease progression Genotype Tests Liver Biochem/function Tests Biopsies – gold standard

15. 15 HCV Treatments Pegylated Interferon + Ribavirin are only FDA approved Rx –Interferon injected weekly –Ribavirin boosts effect, daily pills Sustained Virological Response (SVR): –Genotype 1: 40-50% –Genotypes 2 & 3: 75+%

16. 16 “Follow the Leader” Themes in Which HCV Has Lagged Significantly Behind HIV

17. 17 Unmet Needs and Challenges

18. Hepatitis C Drug Development: 2005 Many others including immune stimulants gene therapy Stage

19. 19 Protease Inhibitors Example: VX-950 or Telapravir Recent US Study – 250 patients –60% cleared virus (vs 40% standard TX only) –67% on 1yr TX = no signs of infection –2X “both” patients stopped TX -> side effects Recent European Study – 334 Patients –After 6 mos, 69% “both” -> undetectable –(vs 46% on standard TX only)

20. 20 Conclusions Despite advances in therapy, many needs remain unmet –Hard-to-treat patients –Nonresponders –Patients excluded from current therapies New antivirals with innovative mechanisms of action may help meet those needs –Monotherapy –In combination with PEG IFN +/- RBV –In combination with new antivirals with different targets Now is the opportunity to develop pipeline therapies toward these many unmet needs

21. Hepatitis C Task Force for Los Angeles County www.hepctaskforcela.org