Hepatitis C:The Next Tsunami

Danny JenkinsCri-Help

Common Ground – The Westside HIV Community Center

We Write the Grants

www.wewritethegrants.com

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

HCV HIV

Lee W, et al. Drugs. 2004;64:693-700.

3

HCV/HIV CoinfectedHIV Monoinfected

70%30%

Overall Prevalence of HCV Among HIV-Infected Persons in the

United States

Thomas D. Hepatology. 2002;36:S201-S209.

4

Hospital Admissions Among HIV-Infected Patients

1995 1996 1997 1998 1999 2000

12

15

8 8 8 8

57

8 8

11

22

57

8

11

20

32

0

5

10

15

20

25

30

35

Opportunisticinfections

IDU-relatedcomplications

Liver-related complications

5-fold increase in liver complications from 1995 to 2000H

osp

ital

izat

ion

s P

er P

atie

nt-

Yea

r F

ollo

w-U

p

Gebo K, et al. J Acquir Immune Defic Syndr. 2003;34:165-173.

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

HCV/HIV Coinfection:An Area of High Medical Need

One third of HIV patients are coinfected with HCV1

– Among HIV-infected IDU, this rises to 50%-90%2

HCV viral load higher in HCV/HIV vs. HCV patients3

HIV accelerates clinical course of HCV-related liver disease – Time to cirrhosis significantly reduced4

– Liver disease is now the leading cause of death in hospitalized AIDS patients5

HCV may also impact the course of HIV disease1. 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

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

Hepatitis C (HCV) Basics

Enters body through direct blood exposure

Attacks liver -> multiples (replicates)

Causes liver inflammation and kills liver cells

9

Natural History of HCV Infection

ExposureExposure(Acute phase)(Acute phase)

ResolvedResolved ChronicChronic

CirrhosisCirrhosisStableStable

SlowlySlowlyProgressiveProgressive

Liver CancerLiver CancerTransplantTransplant

DeathDeath

20%

15% 85%

25%

80%

75%

HIVHIV

Alter MJ. Semin Liver Dis. 1995;15:5-14. Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3).

AlcoholAlcohol2-12 Wks

10-40 Yrs

10

Transmission

Blood to bloodstream Syringes, cookers, tattooing, piercing,

razors, toothbrushes Sexual transmission (very) rare Perinatal 5%

11

Typical Symptoms

Nausea Fatigue Fever Headaches Loss of appetite

Abdominal pain Muscle/joint pain Flu-like symptoms Jaundice Dark urine

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

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

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

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

“Follow the Leader”Themes in Which HCV Has Lagged

Significantly Behind HIV

17

Unmet Needs and

Challenges

Hepatitis C Drug Development: 2005

Many others including immune stimulants

gene therapy

Sta

ge

19

Protease InhibitorsExample: 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

ConclusionsDespite 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

targetsNow is the opportunity to develop pipeline therapies toward

these many unmet needs

Hepatitis C Task Forcefor Los Angeles County

www.hepctaskforcela.org