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