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Hepatitis C & HIV in 2011 Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain.

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Presentation on theme: "Hepatitis C & HIV in 2011 Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain."— Presentation transcript:

1 Hepatitis C & HIV in 2011 Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain

2 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

3 HBV HCV HIV The most prevalent chronic viral infections in humans 7 million

4 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: Hep B, C, D Drug-related toxicity HCV

5 Progression of HCV-related liver fibrosis in HIV patients No HAART HIV-neg Uncontrolled HIV replication Low CD4 counts HAART Metabolic abnormalities Hepatotoxicity of meds years

6 RCT with PegIFN + RBV in HCV/HIV pts APRICOT RIBAVIC No. with Peg+RBV IDUs 62%81% Cirrhotics 15%40% (F3-F4) Genotypes %69% Normal ALT levels 016% Mean CD4 count On HAART 84%82% EOT (ITT) 49%36% SVR (ITT) 40%27%

7 Unique AEs in HCV/HIV-coinfected patients under pegIFN+RBV APRICOTRIBAVIC No Mitochondrial toxicity 2011** 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)

8 Current algorithm for HCV therapy in HIV (peginterferon + ribavirin) W4 W12 W24 W48W72 HCV-RNA neg HCV-RNA pos > 2 log drop in HCV-RNA < 2 log drop in HCV-RNA HCV-RNA neg HCV-RNA pos G2/3 G1/4 Stop G2/3 G1/4 24 weeks therapy 48 weeks therapy 72 weeks therapy Soriano et al. AIDS 2007; 21:

9 Predictors of response to HCV therapy  HCV genotype  Baseline serum HCV-RNA  Liver fibrosis stage  RVR  EVR  IL28B polymorphisms

10 IL28B polymorphisms & hepatitis C outcome Chromosome 19 IL28B gene Interferon 3 Ge et al. Nature 2009; 461: Thomas et al. Nature 2009; 461: Suppiah et al. Nature Gen 2009; 41: Tanaka et al. Nature Gen 2009; 41: SNP: rs (CC, CT, TT) Spontaneous HCV clearance Response to pegIFN+RBV

11 SVR CCCT/TTCCCT/TTCCCT/TTCCCT/TT % AllHCV-3HCV-1HCV % 65% 30% 86% 81% 67% 25% p=0.684 p=0.087 p=0.001 p< AIDS 2010

12 Odds ratio (95% confidence interval) HCV-RNA <600,000 IU/ml HCV genotype 3 rs CC genotype Liver fibrosis stage F0-F p<0.001 p=0.002 p=0.009 Rallon et al. AIDS 2010 IL28B polymorphisms in HIV-HCV coinfection

13 Prometheus index HCV genotype Fibrosis stage (KPa) Serum HCV-RNA IL28B SNPs

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15 A new era for hepatitis C – new diagnostic tools & new weapons DiagnosisTherapy IL28B alleles Non-invasive liver fibrosis methods Viral load HCV geno/subtyping Drug resistance Protease inhibitors Polymerase inhibitors NS5A inhibitors Interferon lambda Alisporivir

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17 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

18 Study 110 Telaprevir in HIV-HCV coinfected pts Week totalNo ARVATV/rEFV % HCV-RNA <10 IU/ml PRT PR Week totalNo ARVATV/rEFV % HCV-RNA <10 IU/ml Sulkowski et al. CROI 2011, LB146

19 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.

20 A shift in care providers for hep C liver hepatologist virus infectologist The HCV doctor

21 8th International Coinfection Workshop Madrid, May 30 - June 1, 2012 Chairmen: Vicente Soriano & Mark Sulkowski HIV HBV HCV

22 Acknowledgments ClinicLaboratory Pablo Barreiro Norma Rallon Pablo Labarga Ana Treviño Luz Martin-Carbonero Carmen de Mendoza Eugenia VispoEva Poveda Jose MedranoSonia Rodriguez-Novoa Jose V FernandezJose Miguel Benito Juan Gonzalez-Lahoz


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