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HV & HIV
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
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.
HBV IN HIV
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
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
unct
ion
Age in years
Progression to cirrhosis
Acute hepatitis C
Treatment of 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
DAAs
Phase 3 PHOTON-1 Study DesignAll-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 TNn=68
GT 1 TNn=114
SOF 400mg + RBV 1000-1200 mg SVR12GT 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
76
0102030405060708090
100
SVR12
HCV
RNA
< 25
IU/m
L (%
)
88
0102030405060708090
100
SVR12
67
0102030405060708090
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 SVR12All-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
Sulkowski MS, et al. AASLD 2014;
Drug-drug interactions
SOF/LDV VIEKIRA