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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
• 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
The most prevalent chronic viral infections in humans
HBV
HCV
400
200
35
7
million
HIV
Deaths in a cohort of 23,441 HIV patients on HAART
HCV
• Hep B, C, D
• Drug-related toxicity
Weber et al. Liver-related deaths in persons infected with HIV: the D:A:D study.
Arch Intern Med 2006; 166: 1632-41.
Progression of HCV-related liver fibrosis in HIV patients
No HAART
Uncontrolled HIV replication
Low CD4 counts
HAART
Metabolic abnormalities
Hepatotoxicity of meds
HIV-neg
years
RCT with PegIFN + RBV in HCV/HIV pts
APRICOT
RIBAVIC
No. with Peg+RBV
IDUs
Cirrhotics
Genotypes 1-4
288
62%
15%
67%
194
81%
40%(F3-F4)
69%
Normal ALT levels
Mean CD4 count
On HAART
0
520
84%
16%
525
82%
EOT (ITT)
SVR (ITT)
49%
40%
36%
27%
Unique AEs in HCV/HIV-coinfected
patients under pegIFN+RBV
APRICOT RIBAVIC
No.
Mitochondrial
toxicity
Hepatic
decompensation
860
383
20
11**
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
G2/3
HCV-RNA
neg
W48
W24
24 weeks
therapy
G1/4
> 2 log drop
in HCV-RNA
HCV-RNA
pos
HCV-RNA
neg
HCV-RNA
pos
< 2 log drop
in HCV-RNA
W72
G2/3
G1/4
48 weeks
therapy
72 weeks
therapy
Stop
Stop
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
Response to
pegIFN+RBV
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.
AIDS 2010
SVR
86%
81%
p<0.0001
75%
p=0.684
p=0.001
p=0.087
65%
67%
38%
30%
25%
CC CT/TT
CC CT/TT
CC CT/TT
CC CT/TT
75 89
All
164
34 61
HCV-1
95
35 16
HCV-3
51
6 12
HCV-4
18
IL28B polymorphisms in HIV-HCV coinfection
11.9
HCV-RNA <600,000 IU/ml
p<0.001
8.0
HCV genotype 3
3.7
rs12979860 CC genotype
p=0.002
3.5
Liver fibrosis stage F0-F2
0
5
p<0.001
p=0.009
10
15
20
25
30
35
40
Odds ratio (95% confidence interval)
Rallon et al. AIDS 2010
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
• IL28B alleles
• Non-invasive liver
fibrosis methods
• Viral load
• HCV geno/subtyping
• Drug resistance
Therapy
•
•
•
•
•
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 110
Telaprevir in HIV-HCV coinfected pts
PRT
% HCV-RNA
<10 IU/ml
PR
% HCV-RNA
<10 IU/ml
75
70
75
71
71
68
64
57
14
5
37 22
total
0
0
7 6
14 8
No ARV ATV/r
Week 4
17
12
12
7 6
14 8
No ARV ATV/r
16 8
EFV
12
16 8
EFV
37 22
total
Week 12
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
virus
hepatologist
infectologist
The HCV doctor
8th International Coinfection Workshop
Madrid, May 30 - June 1, 2012
Chairmen: Vicente Soriano & Mark Sulkowski
HIV
www.virology-education.com
HBV
HCV
Acknowledgments
Clinic
Laboratory
Pablo Barreiro
Pablo Labarga
Luz Martin-Carbonero
Eugenia Vispo
Jose Medrano
Jose V Fernandez
Norma Rallon
Ana Treviño
Carmen de Mendoza
Eva Poveda
Sonia Rodriguez-Novoa
Jose Miguel Benito
Juan Gonzalez-Lahoz