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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