Hépatites Virales C et
B et Infection par le
VIH
Benhamou Yves
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 ...
HCV in HIV
Fibrosis progression
Progression to cirrhosis
1.00

Hazard function

4,682 patients

180 HIV-HCV
701 Alcohol
812 HBV
382 Hemochromatosis
2,313 ...
Treatment for HCV IN HIV
Fibrosis stage (Metavir fibrosis units)

SVR = regression, NR = progression ?

4
3

NR/R (n=63)
Untreated (n=29)

2
1

SVR...
TELAPREVIR
BOCEPREVIR
Faldaprevir
Acute hepatitis C
Acute HCV among HIV+ MSM

USA1,2: 54 cases
Prevalence chronic HCV/HIV12-14
15 – 30%: 180.000 – 360.000

Europe: 951 cases
...
HBV IN HIV
Prevalence of HBsAg+ in HIV Infected
Patients
EuroSIDA Cohort (n= 9802) :
 Patients screened for HBsAg: 5883 (60%)
 HBsA...
Influence of HIV on CHB
In the Pre HAART era, HIV in HBsAg positive patients (compared to
HBV mono-infected):
Increased th...
Treatment of HBV in HIV Co-infected Patients
Licensed for
HIV
Interferon (IFN)
Lamivudine (LAM)

Emtricitabine (FTC)
Entec...
Tenofovir Disoproxil Fumarate
TDF vs. TDF+LAM (48 weeks)
TDF

100

TDF + LAM (48 weeks)

TDF+LAM

LAM
Naive
(n=9)

42/50

...
Tenofovir Disoproxil Fumarate
TDF- vs LAM- containing HAART in ARV-naïve HIV/HBeAg+ Co-infected Patients (TICO Study):
Ran...
Treatment Algorithm
Patients with Compensated Liver Disease and
No Indication for HIV Therapy (CD4 count >350/µL)
HBV DNA
...
Treatment Algorithm
Patients with Compensated Liver Disease and
Indication for HIV Therapy (CD4 count <350/µL)
HBV DNA

HB...
Conclusions
Viral hepatitis coinfections are major factors of
mortality and morbidity in the HIV infected population

It i...
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
Benhamou y  hiv  et hep vir 2014
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Benhamou y hiv et hep vir 2014

  1. 1. Hépatites Virales C et B et Infection par le VIH Benhamou Yves
  2. 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. 3. HCV in HIV
  4. 4. Fibrosis progression
  5. 5. 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
  6. 6. Treatment for HCV IN HIV
  7. 7. 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
  8. 8. TELAPREVIR
  9. 9. BOCEPREVIR
  10. 10. Faldaprevir
  11. 11. Acute hepatitis C
  12. 12. 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.
  13. 13. HBV IN HIV
  14. 14. 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.
  15. 15. 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
  16. 16. 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              
  17. 17. 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.
  18. 18. 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
  19. 19. 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.
  20. 20. 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.
  21. 21. 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

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