Hepatitis C & HIV in 2011

Vincent SorianoInfectious Diseases DepartmentHospital Carlos III, Madrid, Spain

HCV epidemiology

• 2-3% of the world population.• >40% undiagnosed • Routes of infection: sporadic >50%• Risk factors: transfusions <1990; IVDU• 30% of chronic carriers will develop cirrhosis• HCV is the primary reason for liver transplantation• HCV is the major cause of liver cancer• No vaccine• Only curable (eradication) chronic viral infection

400200

35

HBV

HCV

HIV

The most prevalent chronic viral infections in humans

7 million

Deaths in a cohort of 23,441 HIV patients on HAART

Weber et al. Liver-related deaths in persons infected with HIV: the D:A:D study. Arch Intern Med 2006; 166: 1632-41.

• Hep B, C, D• Drug-related toxicityHCV

Progression of HCV-related liver fibrosis in HIV patients

No HAART

HIV-neg

Uncontrolled HIV replicationLow CD4 counts HAART

Metabolic abnormalitiesHepatotoxicity of meds

years

RCT with PegIFN + RBV in HCV/HIV pts

APRICOT RIBAVIC

No. with Peg+RBV 288 194 IDUs 62% 81% Cirrhotics 15% 40%(F3-F4)

Genotypes 1-4 67% 69%

Normal ALT levels 0 16% Mean CD4 count 520 525 On HAART 84% 82%

EOT (ITT) 49% 36% SVR (ITT) 40% 27%

Unique AEs in HCV/HIV-coinfected patients under pegIFN+RBV

APRICOT RIBAVIC

No. 860 383Mitochondrial toxicity 20 11**Hepatic decompensation 14* 7***

* All seen in cirrhotics. Overall, it affected 10% of cirrhotics; associated to ddI (+ RBV)** 1 out of 5 patients treated with ddI*** Associated with ddI and cirrhosis (OR = 9)

Current algorithm for HCV therapy in HIV(peginterferon + ribavirin)

W4 W12 W24 W48 W72

HCV-RNAneg

HCV-RNApos

> 2 log dropin HCV-RNA

< 2 log dropin HCV-RNA

HCV-RNAneg

HCV-RNApos

G2/3

G1/4

Stop

Stop

G2/3

G1/4

24 weekstherapy

48 weekstherapy

72 weekstherapy

Soriano et al. AIDS 2007; 21: 1073-89.

Predictors of response to HCV therapy

HCV genotype Baseline serum HCV-RNA Liver fibrosis stage RVR EVR

IL28B polymorphisms

IL28B polymorphisms & hepatitis C outcome

Chromosome 19

IL28B geneInterferon 3

Ge et al. Nature 2009; 461: 399-401.Thomas et al. Nature 2009; 461: 798-802.Suppiah et al. Nature Gen 2009; 41: 1100-4.Tanaka et al. Nature Gen 2009; 41: 1105-9.

SNP: rs12979860 (CC, CT, TT)

SpontaneousHCV clearance

Response topegIFN+RBV

SVR

CC CT/TT CC CT/TT CC CT/TT CC CT/TT34 61 35 16 6 1275 89

75%

All HCV-3HCV-1 HCV-4164 5195 18

38%

65%

30%

86%81%

67%

25%

p=0.684

p=0.087p=0.001

p<0.0001

AIDS 2010

Odds ratio (95% confidence interval)

HCV-RNA <600,000 IU/ml

HCV genotype 3

rs12979860 CC genotype

Liver fibrosis stage F0-F2

0 5 10 15 20 25 30 35 40

11.9

8.0

3.7

3.5

p<0.001

p<0.001

p=0.002

p=0.009

Rallon et al. AIDS 2010

IL28B polymorphisms in HIV-HCV coinfection

Prometheus index• HCV genotype• Fibrosis stage

(KPa)• Serum HCV-RNA• IL28B SNPs

http://ideasydesarrollo.com/fundacion/prometheusindex.php

http://ideasydesarrollo.com/fundacion/prometheusindex.php

A new era for hepatitis C – new diagnostic tools & new weapons

Diagnosis Therapy

• IL28B alleles• Non-invasive liver fibrosis methods• Viral load• HCV geno/subtyping• Drug resistance

• Protease inhibitors• Polymerase inhibitors• NS5A inhibitors• Interferon lambda• Alisporivir

Challenges using DAA in HIV-HCV coinfection

More elevated HCV load. More virological failures?

Faster selection of drug resistance?

Drug-drug interactions

Overlapping toxicities – rash & anemia

Drug compliance with polymedication

Additional cost

Study 110Telaprevir in HIV-HCV coinfected pts

Week 4

3722 7 6 14 8 16 8

70

5

71

0

64

0

75

12

total No ARV ATV/r EFV

% HCV-RNA <10 IU/ml

PRT PR

Week 12

3722 7 6 14 8 16 8

68

14

71

17

57

12

75

12

total No ARV ATV/r EFV

% HCV-RNA <10 IU/ml

Sulkowski et al. CROI 2011, LB146

Implications of widespread use of DAA

Shift in HCV genotypes in the infected population, being other genos replacing geno 1.

Changes in HCV-infected populations, with accumulation in poor regions and/or communities within rich countries.

Growing number of patients with drug-resistant mutant viruses and potential for transmission.

A shift in care providers for hep C

liver

hepatologist

virus

infectologist

The HCV doctor

8th International Coinfection Workshop

Madrid, May 30 - June 1, 2012Chairmen: Vicente Soriano & Mark Sulkowski

HIVHBVHCV

www.virology-education.com

 

Acknowledgments

Clinic LaboratoryPablo Barreiro Norma Rallon Pablo Labarga Ana Treviño Luz Martin-Carbonero Carmen de Mendoza Eugenia Vispo Eva PovedaJose Medrano Sonia Rodriguez-NovoaJose V Fernandez Jose Miguel BenitoJuan Gonzalez-Lahoz