Benhamou hiv hcv 07 03 15 final

1. HV & HIV

2. 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

4. 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.

5. HBV IN HIV

6. 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

7. 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)
 

8. 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<3
log
AST<45
U/L
HBeAg
loss
HBsAg
loss
Patients(%)
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)

9. Matthews G et al. Hepatology 2008
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
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

10. 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 DNA
2000 IU/mL
HBV DNA
HBV DNA
<2000 IU/mL
ALT Elevated
ALT 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.

11. 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 including
TDF+3T/FTC
Substitute one NRTI by
TDF 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 including
TDF+LAM/FTC
*If feasible and appropriate from the perspective
of maintaining HIV suppression.
Refer patient for liver
transplantation
evaluation if
decompensation
HBV DNA

12. 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

13. HCV in HIV

14. Fibrosis progression

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

17. Acute hepatitis C

18. Treatment of HCV IN
HIV

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

21. DAAs

22. Phase 3 PHOTON-1 Study Design
All-Oral Therapy of SOF + RBV in HCV/HIV Co-infection
Sulkowski MS, et al. AASLD 2013. Washington, DC. Oral #212
0 12 24 36
SOF 400mg + RBV 1000-1200mg SVR12
SOF 400mg + RBV 1000-1200 mg SVR12
Study Week
GT 2,3 TN
n=68
GT 1 TN
n=114
SOF 400mg + RBV 1000-1200 mg SVR12
GT 2,3 TE
n=41
 Broad inclusion criteria
– Cirrhosis permitted with no platelet cutoff
– Hemoglobin: ≥12 mg/dL (males); ≥11 mg/dL (females)
 Wide range of ART regimens allowed
– Undetectable HIV RNA for >8 weeks on stable ART regimen
 Baseline CD4 count
– ART treated: CD4 T-cell count >200 cells/mm3 and HIV RNA < 50 c/mL
– ART untreated: CD4 T-cell count >500 cells/mm3
No response guided therapy

23. 76
0
10
20
30
40
50
60
70
80
90
100
SVR12
HCVRNA<25IU/mL(%)
88
0
10
20
30
40
50
60
70
80
90
100
SVR12
67
0
10
20
30
40
50
60
70
80
90
100
SVR12
GT1 TN1
SOF + RBV
x24 weeks
GT2 TN1
SOF + RBV
x12 weeks
GT3 TN1
SOF + RBV
x12 weeks
GT3 TE2
SOF + RBV
x24 weeks
92
0
20
40
60
80
100
SVR12
1. Sulkowski MS, et al. AASLD 2013. Washington, DC. Oral #212;
2. SOVALDI™ [PI]. Gilead Sciences, Inc. Foster City, CA December 2013
87/114 23/26 28/42 12/13
PHOTON-1 SVR12
All-Oral Therapy of SOF + RBV in GT1, 2, 3 HCV Treatment-Naive
and GT 3 Treatment-Experienced/HIV Co-infection
 An all-oral regimen of SOF + RBV for 12–24 weeks resulted in high SVR12 rates in TN GT 1, 2 and 3 and TE
GT 3 CHC with HIV coinfection – with SVR12 rates similar to mono-infection
 No HCV resistance was observed
– No S282T mutations were observed in virologic failures via deep sequencing
 Two patients had HCV breakthrough; both had documented non-adherence to SOF
 Two other patients had transient HIV breakthrough; both had documented non-adherence to ART

24. Sulkowski MS, et al. AASLD 2014;

29. Drug-drug interactions
Traitement anti-VHC
Simeprevir Daclatasvir Sofosbuvir
Traitementanti-VIH
INTI
zidovudine
abacavir
Lamivudine/
emtricitabine
tenofovir
INNTI
Efavirenz ↑ DCV de 50%
Nevirapine ? ? ?
Etravirine ? ? ?
Rilpivirine
IP
Darunavir/r
Atazanavir/r ? ↓ DCV de 50%
Lopinavir/r ? ? ?
AI
Raltegravir
Dolutegravir ? ? ?
Elvitegravir ? ?
CCR5
Maraviroc ? ?
Ne pas utiliser en raison d’interactions importantes
Ne pas utiliser car pas de données d’interactions disponibles
Utiliser avec précaution (effectuer si besoin des dosages pharmacologiques)
Pas d’interaction rapportée, utilisation sans risque
?

31. SOF/LDV VIEKIRA