1. Hépatites Virales C et
B et Infection par le
VIH
Benhamou Yves

2. HIV, Hepatitis B and C: global prevalence
350.000.000
170.000.000
33.000.000
2-4.000.000
4-5.000.000
1. WHO Factsheets HBV, HCV, HIV; 2. Alter MJ. J Hepatol 2006; 44(Suppl.1): S6-S9.

3. HCV in HIV

6. Fibrosis progression

7. Progression to cirrhosis
1.00
Hazard function
4,682 patients
180 HIV-HCV
701 Alcohol
812 HBV
382 Hemochromatosis
2,313 HCV
93 Steatosis BMI>25
200 PBC
0
20
40
Age in years
60
80
Poynard, T. et al. J Hepatol 2003;38:257-265

9. Treatment for HCV IN HIV

11. Fibrosis stage (Metavir fibrosis units)
SVR = regression, NR = progression ?
4
3
NR/R (n=63)
Untreated (n=29)
2
1
SVR (n=34)
0
-1
0
5
10
15
20
Time (yr)
Ingiliz, Benhamou et al., J Hepatol, submitted, under review

13. TELAPREVIR

14. BOCEPREVIR

20. Faldaprevir

26. Acute hepatitis C

27. Acute HCV among HIV+ MSM
USA1,2: 54 cases
Prevalence chronic HCV/HIV12-14
15 – 30%: 180.000 – 360.000
Europe: 951 cases
Prevalence chronic HCV/HIV14,15
25%: 185.500
-UK3,4 552
-Germany5 157
-France6,7 117
-Netherlands8 81
-Swiss9 23
-Italy10 21
Australia11: 28 cases
Prevalence chronic HCV/HIV16
< 1%: 1.000
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.

28. HBV IN HIV

29. 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.

30. Influence of HIV on CHB
In the Pre HAART era, HIV in HBsAg positive patients (compared to
HBV 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

31. Treatment of HBV in HIV Co-infected Patients
Licensed for
HIV
Interferon (IFN)
Lamivudine (LAM)
Emtricitabine (FTC)
Entecavir (ETV)
Telbivudine (LDT)
Adefovir dipivoxil (ADV)
Tenofovir disoproxil fumarate
(TDF)
HBV















32. Tenofovir Disoproxil Fumarate
TDF vs. TDF+LAM (48 weeks)
TDF
100
TDF + LAM (48 weeks)
TDF+LAM
LAM
Naive
(n=9)
42/50
Patients (%)
80
19 / 2 5
LAM
Experienced
(n=47)
29/50
14 / 2 5
60
40
HBV DNA <15
UI/mL
9/25
9
41
Mean time to
DNA < LOD
(weeks)
49
67
12 / 5 0
20
3 / 5 0 1/ 2 5
0
DNA<3
log
AST<45 HBeAg
U/L
loss
Schmutz G, et al. AIDS. 2006.
HBsAg
loss
Tuma R, et al. AASLD 2008, Abstract 967.

33. 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
W48 outcomes
LAM
N=12
TDF
N=12
TDF+LAM
N=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
Matthews G et al. Hepatology 2008

34. Treatment Algorithm
Patients with Compensated Liver Disease and
No Indication for HIV Therapy (CD4 count >350/µL)
HBV DNA
HBV DNA
<2000 IU/mL
HBV DNA
2000 IU/mL
ALT Normal
• No treatment
• Monitor every
6–12 months
• Monitor ALT every
3-12 months
• Consider biopsy
and treat if disease
present
ALT Elevated
• 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.

35. Treatment Algorithm
Patients with Compensated Liver Disease and
Indication for HIV Therapy (CD4 count <350/µL)
HBV DNA
HBV DNA
≥2000 IU/ml
Patients without
HBV-associated
LAM resistance
HAART including
TDF+3T/FTC
Patients with
cirrhosis
HBV DNA
<2000 IU/ml
Patients with
HBV-associated
LAM resistance
Substitute one NRTI by
TDF or add TDF*
HAART including
TDF+LAM/FTC
HAART regimen
of choice
Refer patient for liver
transplantation
evaluation if
decompensation
*If feasible and appropriate from the perspective
of maintaining HIV suppression.
ECC Statement. J Hepatol. 2005.
Rockstroh et al. HIV Medicine 2008.

36. 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