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Hépatites Virales C et B et Infection par le
VIH
Benhamou Yves
HIV, Hepatitis B and C: global prevalence
1. WHO Factsheets HBV, HCV, HIV; 2. Alter MJ. J Hepatol 2006; 44(Suppl.1): S6-S9.
350.000.000
170.000.000
33.000.000
2-4.000.000
4-5.000.000
HCV in HIV
Fibrosis progression
Poynard, T. et al. J Hepatol 2003;38:257-265
4,682 patients
180 HIV-HCV701 Alcohol812 HBV382 Hemochromatosis2,313 HCV 93 Steatosis BMI>25200 PBC
1.00
0 20 40 60 80
Haza
rd f
un
ctio
n
Age in years
Progression to cirrhosis
Treatment for HCV IN HIV
SVR = regression, NR = progression ?
-1
0
1
2
3
4
0 5 10 15 20
Time (yr)
Fibr
osis
stag
e (M
etav
ir fib
rosi
s un
its)
Untreated (n=29)
SVR (n=34)
NR/R (n=63)
Ingiliz, Benhamou et al., J Hepatol, submitted, under review
TELAPREVIR
BOCEPREVIR
Faldaprevir
Acute hepatitis C
Acute HCV among HIV+ MSM
1.Luetkemeyer JAIDS 2006; 2.Fierer 5th Works. HIV & Hep. Coinf. 2009; 3.Giraudon Sex Transm Infect 2008; 4.Ruf Eurosurveill 2008; 5. Vogel CID 2009; 6.Gambotti Euro Surveill 2005; 7.Larsen AASLD 2007; 8.Urbanus AIDS 2009; 9.Rauch CID 2005; 10.Gallotta 4th Works. HIV & Hep. Coinf. 2008; 11.Matthews CID 2009; 12. Sherman CID 2002; 13: Backus JAIDS 2005; 14: UNAIDS Report 2008; 15: Soriano JID 2008; 16: NCHECR Report 2008.
Europe: 951 casesPrevalence chronic HCV/HIV14,15
25%: 185.500
-UK3,4 552-Germany5 157-France6,7 117-Netherlands8 81-Swiss9 23-Italy10 21
Australia11: 28 casesPrevalence chronic HCV/HIV16
< 1%: 1.000
USA1,2: 54 casesPrevalence chronic HCV/HIV12-14
15 – 30%: 180.000 – 360.000
HBV IN HIV
Prevalence of HBsAg+ in HIV Infected Patients
· EuroSIDA Cohort (n= 9802) :
Patients screened for HBsAg: 5883 (60%)
HBsAg+: 530 (9%)
- South: 9.1%
- Central: 9.2%
- North: 9.7%
- East: 6%
Konopnicki D, et al. AIDS. 2005.
Influence of HIV on CHBIn the Pre HAART era, HIV in HBsAg positive patients (compared toHBV mono-infected):
· Increased the risk of chronic infection after contamination
· Reduced the seroconversion rates to anti-HBe and anti- HBs
· Increased HBV replication
· Frequent reactivation related to CD4 decline
· Accelerated fibrosis progression
· Increased risk of liver decompensation, HCC and liver death
Bodsworth, JID 1989 ; Hadler, JID 1991 ; Krogsgaard, Hepatology 1987 ; Bodsworth, JID 1989 ; Gilson, AIDS 1997. Piroth, J Hepatol 2002; Vogel Cancer Res 1991; Corallini Cncer Res 1993 ; Altavilla Am J Pathol 2000 ; Bodsworth, JID 1989 ; Mills,
Gastroenterol 1990 ; Goldin, J Clin Pathol 1990 ; Gilson, AIDS 1997 ; Thio, Lancet 2002 ; Di Martino, Gastroenterol 2002; Colin Hepatol 1999; Perillo, Ann Int Med 1986 ; McDonald, J Hepatol 1987
Treatment of HBV in HIV Co-infected Patients
Licensed for
HIV HBV
Interferon (IFN) Lamivudine (LAM) Emtricitabine (FTC) Entecavir (ETV) Telbivudine (LDT) Adefovir dipivoxil (ADV) Tenofovir disoproxil fumarate (TDF)
TDF vs. TDF+LAM (48 weeks)
3/50
12/50
29/50
42/50
1/25
9/25
14/25
19/25
0
20
40
60
80
100
DNA<3log
AST<45U/L
HBeAgloss
HBsAgloss
Pat
ien
ts (
%)
TDF TDF+LAM
Schmutz G, et al. AIDS. 2006.
LAM Naive(n=9)
LAM Experienced(n=47)
HBV DNA <15 UI/mL
9 41
Mean time to DNA < LOD (weeks)
49 67
Tuma R, et al. AASLD 2008, Abstract 967.
Tenofovir Disoproxil Fumarate
TDF + LAM (48 weeks)
Matthews G et al. Hepatology 2008
W48 outcomesLAMN=12
TDFN=12
TDF+LAMN=12
p
Median DNA Reduction 4.07 4.57 4.73 .7
DNA <3 log 46% 92% 91% .01
HBeAg loss 3 1 3
Anti-HBe Seroconversion 1 1 3
HBsAg loss 1 1 1
Tenofovir Disoproxil Fumarate
TDF- vs LAM- containing HAART in ARV-naïve HIV/HBeAg+ Co-infected Patients (TICO Study):
Randomized Thai trial (1:1:1) of LAM vs TDF vs LAM/TDF within an EFV-based HAART regimen
Treatment Algorithm Patients with Compensated Liver Disease and
No Indication for HIV Therapy (CD4 count >350/µL)
• No treatment
• Monitor every 6–12 months
HBV DNA2000 IU/mL
HBV DNA
HBV DNA<2000 IU/mL
ALT ElevatedALT Normal
• Monitor ALT every 3-12 months
• Consider biopsy and treat if disease present
• PEG IFN• LdT (if HBV DNA>LOD at w24 add ADV)• ADV+LdT• Early HAART initiation –TDF+LAM/FTC
ECC Statement. J Hepatol. 2005.Rockstroh et al. HIV Medicine 2008.
Treatment Algorithm Patients with Compensated Liver Disease and Indication for HIV Therapy (CD4 count <350/µL)
HBV DNA≥2000 IU/ml
HBV DNA<2000 IU/ml
HAART includingTDF+3T/FTC
Substitute one NRTI byTDF or add TDF*
Patients without HBV-associated LAM resistance
Patients with cirrhosis
ECC Statement. J Hepatol. 2005.Rockstroh et al. HIV Medicine 2008.
Patients with HBV-associated LAM resistance HAART regimen
of choice
HAART includingTDF+LAM/FTC
*If feasible and appropriate from the perspective
of maintaining HIV suppression.
Refer patient for liver transplantation
evaluation if decompensation
HBV DNA
Conclusions
· Viral hepatitis coinfections are major factors of mortality and morbidity in the HIV infected population
· It is crucial to determine those patients who are in need for treatment
· Viral and host factors can predict the chance of cure
· DAAs for HCV will soon be available but lack data on HIV coinfection
· Tenofovir is the actual agent of choice in HBV coinfection