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Hepatitis C & HIV in 2011

Hepatitis C & HIV in 2011. Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain. HCV epidemiology. 2-3% of the world population. >40% undiagnosed Routes of infection: sporadic >50% Risk factors: transfusions <1990; IVDU

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Hepatitis C & HIV in 2011

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  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. The most prevalent chronic viral infections in humans HBV HCV 400 200 35 7 million HIV

  4. Hep B, C, D • Drug-related toxicity Deaths in a cohort of 23,441 HIV patients on HAART HCV Weber et al. Liver-related deaths in persons infected with HIV: the D:A:D study. Arch Intern Med 2006; 166: 1632-41.

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

  6. 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%

  7. Unique AEs in HCV/HIV-coinfected patients under pegIFN+RBV * 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. W12 W48 W72 W4 W24 G2/3 24 weeks therapy HCV-RNA neg G1/4 48 weeks therapy G2/3 HCV-RNA neg G1/4 72 weeks therapy > 2 log drop in HCV-RNA HCV-RNA pos Stop HCV-RNA pos < 2 log drop in HCV-RNA Stop Current algorithm for HCV therapy in HIV(peginterferon + ribavirin) Soriano et al. AIDS 2007; 21: 1073-89.

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

  10. Response to pegIFN+RBV IL28B polymorphisms & hepatitis C outcome IL28B gene Interferon 3 SNP: rs12979860 (CC, CT, TT) Spontaneous HCV clearance Chromosome 19 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.

  11. p=0.684 SVR 86% p<0.0001 81% p=0.001 p=0.087 75% 67% 65% 38% 30% 25% CC CT/TT CC CT/TT CC CT/TT CC CT/TT 89 61 12 75 34 16 6 35 All HCV-1 HCV-3 HCV-4 164 95 51 18 AIDS 2010

  12. 11.9 HCV-RNA <600,000 IU/ml p<0.001 8.0 HCV genotype 3 p<0.001 3.7 rs12979860 CC genotype p=0.002 3.5 p=0.009 Liver fibrosis stage F0-F2 0 5 10 15 20 25 30 35 40 Odds ratio (95% confidence interval) IL28B polymorphisms in HIV-HCV coinfection Rallon et al. AIDS 2010

  13. Prometheusindex • HCV genotype • Fibrosis stage (KPa) • Serum HCV-RNA • IL28B SNPs http://ideasydesarrollo.com/fundacion/prometheusindex.php

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

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

  16. Challenges using DAA in HIV-HCV coinfection • More elevated HCV load. More virologicalfailures? • Fasterselection of drugresistance? • Drug-druginteractions • Overlappingtoxicities – rash & anemia • Drugcompliancewithpolymedication • Additionalcost

  17. Study 110Telaprevir in HIV-HCV coinfectedpts PRT PR % HCV-RNA <10 IU/ml % HCV-RNA <10 IU/ml 75 75 71 70 71 68 64 57 17 14 12 12 12 5 0 0 37 22 7 6 14 8 16 8 37 22 7 6 14 8 16 8 total No ARV ATV/r EFV total No ARV ATV/r EFV Week 12 Week 4 Sulkowski et al. CROI 2011, LB146

  18. 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.

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

  20. HBV HCV HIV 8th International Coinfection Workshop Madrid, May 30 - June 1, 2012 Chairmen: Vicente Soriano & Mark Sulkowski www.virology-education.com

  21. Acknowledgments ClinicLaboratory Pablo Barreiro Norma Rallon Pablo Labarga Ana Treviño Luz Martin-Carbonero Carmen de Mendoza Eugenia Vispo Eva Poveda Jose Medrano Sonia Rodriguez-Novoa Jose V Fernandez Jose Miguel Benito Juan Gonzalez-Lahoz

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