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Jürgen Rockstroh
Medizinische Klinik I
Universitätsklinikum Bonn
3rd. Paris Hepatitis Conference, Paris, 19. January 2009
Management of HIV-HCV coinfected patients
Stanislas Pol, MD, PhDUnité d’Hépatologie &
Inserm U-567Hôpital Cochin, Paris, France
Prevalence of Hepatitis C (1960/5957 patients = 33%)
Regions:southcentralnortheast
South: 695 = 41,4 %
North: 359 = 23,2 %
Central: 293 = 19,6 %
East: 613 = 46,9 %
Rockstroh J et al.,
J Inf Dis 2005
Prevalence of Hepatitis Coinfection in Germany
Patients from the German Competence Network HIV/AIDS with complete hepatitis serology, HAART treatment information and still under observation and accesible in the cohort after the 1.01.2007 were included
Overall 2692 patients were evaluated• a chronic hepatitis B infection (persistent HBs-
Ag+) was present in 157 patients (5.8%)• a chronic hepatitis C infection was determined
in 351 Patienten (13.0%)
Rockstroh J et al. DÖAK 2007;C19
Acute Hepatitis C cases reported in Germany
Berlin 110 Hamburg 25 NRW 12 Hessen 6 Bayern / BW 3
Risk factors in the transmission of acute HCV in HIV+
Schmidt et al. IAS 2007 MOPEB037
Question
If an HIV patient gets infected with hepatitis C how high is his probability of spontaneously clearing HCV?
1. > 50% (yellow)
2. 40% (green)
3. < 25% (red)
Hepatitis coinfection in EuroSIDA
• HCV genotype distribution and percentage of naturally cleared HCV infection within EuroSIDA
• Studied relationship between HCV genotype and/or HCV RNA level and risk for developing liver disease related death, or all cause mortality
Results
• Of 2263 HCVAb+ patients, 1677 (74.1%) were serum HCV RNA+ (95% CI: 71–78%)
Soriano V, et al. 11th EACS, Madrid 2007; PS8/1, Soriano V et al. Clin Infect Dis 2008
Northern Europe
0%
20%
40%
60%
1 2 3 4
Southern Europe Central Europe Eastern Europe
1 2 3 4 1 2 3 4 1 2 3 4
Distribution of HCV by genotype (1–4) in European regions
55
1a1a
33
22
44 66
1 (other)1 (other)
1b1b
GGeenotypes VHCnotypes VHC,, France, 2003 France, 2003
4aY116044aY116044aFrSSD254aFrSSD25
4d FRSSD504d FRSSD504d FRSSD1714d FRSSD171
4d FRSSD654d FRSSD654d MRS954d MRS95
4d P9 RCP4d P9 RCP4d FRSSD584d FRSSD58
4d FRSSD374d FRSSD37PAT 9- PAT 9- 20032003
PAT 5- PAT 5- 20012001PAT 10-PAT 10-20022002PAT 12- PAT 12- 20042004
PAT 4- PAT 4- 20022002PAT 8- PAT 8- 20022002
PAT 2- PAT 2- 20022002PAT 7- PAT 7- 20032003PAT 11- PAT 11- 20032003PAT 1- PAT 1- 20022002
900900
10001000
10001000
999999
PhylogPhylogéénnie ie NS5b : 10/12 patients NS5b : 10/12 patients avec gavec génotype 4d au CHU Neckerénotype 4d au CHU Necker
La comparaison des La comparaison des ssééquences NS5b confirme quences NS5b confirme l’homogl’homogééneitneité des souchesé des souches (variabilit(variabilité é moyenne : 0moyenne : 0,,01 %)01 %)
J Serpaggi, AIDS 2006J Serpaggi, AIDS 2006
Clusters of sexual transmission
Treatment of acute hepatitis C
Acute hepatitisC
Jaundice
HCV RNA at W12PEG-IFN and ribavirin 24 weeks
No Yes
+
No treatment
-
HIV +Yes
Natural history of acute HCV in HIV-infected patients
Week 12127 HCV PCR +
25 declined treatment
Week 485 PCR –
20 PCR +
14 remained untreated
Week 486 PCR –8 PCR +
Week 1223 HCV PCR-
150 patients
S 12127 PCR +
25 refused treatment
S 485 PCR –
20 PCR +
Spontaneous HCV Clearance at W48=11/150 overall (7%)=11/39 untreated (28%)
14 not treated
S 486 PCR –8 PCR +
S 1223 PCR -
150 patients
Azwa et al, EACS Madrid 2007Azwa et al, EACS Madrid 2007
PegIFN + ribavirin combination in acute hepatitis
All patientsn=44
Male 43 (98%)
Mean age (Years) 38.5 (33.5 – 43.5)
Transmission-risk• IVDU• IVDU and UPSI• UPSI• unknown
1 (2%)2 (5%)
34 (77%)7 (16%)
Reason for HCV-Testing• abnormal LFT• Symptoms hepatitis• History of transmission risk (IVDU, positive partner)• routine screen
30 (68%)4 (9%)
8 (18%)2 (5%)
Other STD at diagnosis of HCV 6 (14%)
Use of HAART 26 (59%)
HCV-RNA (IU/ml, log10) 6.3 (5.4 – 6.9)
ALT (IU/ml) 326 (154 – 565)
CD4 cell-count (/µl) 400 (350 – 614)
HIV-RNA (copies/ml, log10) 1.7 (1.7 – 4.5)
Time between diagnosis and treatment (weeks) 11 (4 – 25)
Duration of treatment (weeks) 24 (20 – 43)
All patientsn=44
Male 43 (98%)
Mean age (Years) 38.5 (33.5 – 43.5)
Transmission-risk• IVDU• IVDU and UPSI• UPSI• unknown
1 (2%)2 (5%)
34 (77%)7 (16%)
Reason for HCV-Testing• abnormal LFT• Symptoms hepatitis• History of transmission risk (IVDU, positive partner)• routine screen
30 (68%)4 (9%)
8 (18%)2 (5%)
Other STD at diagnosis of HCV 6 (14%)
Use of HAART 26 (59%)
HCV-RNA (IU/ml, log10) 6.3 (5.4 – 6.9)
ALT (IU/ml) 326 (154 – 565)
CD4 cell-count (/µl) 400 (350 – 614)
HIV-RNA (copies/ml, log10) 1.7 (1.7 – 4.5)
Time between diagnosis and treatment (weeks) 11 (4 – 25)
Duration of treatment (weeks) 24 (20 – 43)
SVR
n=25
no SVR
n=19
p-value
Characteristic acute HCV• patient age (years)• symptomatic hepatitis• Max ALT elevation (IU/ml)•HCV-RNA (IU/ml, log10)
38 (33 – 45)4/25 (16%)
362 (141–592)6.33 (5.24-6.89)
39 (34 – 43)1/19 (5%)
250 (157–555)6.26(5.36-6.86)
0.7410.3700.6550.790
Characteristic HIV• Use of HAART• HIV-RNA < LOD• HIV-RNA (cop/ml, log10)• CD4 cell-count (/µl)
14/25 (56%)14/24 (58%)
1.70(1.70 – 4.75)389 (335–612)
12/19 (63%)8/14 (57%)
2.29(1.70-4.53)452 (362–618)
0.7601.0000.8080.636
HCV-Treatment • delay treatment (weeks)• start within 12 weeks• start within 6 months• HCV-RNA neg. week 4• duration treatment (weeks)
19 (7 – 26)11/25 (44%)20/25 (80%)18/20 (90%)27 (23 – 47)
8 (3 – 18)13/19 (68%)18/19 (95%)7/24 (29%)
24 (14 – 33)
0.0810.1350.213
<0.0010.237
SVR
n=25
no SVR
n=19
p-value
Characteristic acute HCV• patient age (years)• symptomatic hepatitis• Max ALT elevation (IU/ml)•HCV-RNA (IU/ml, log10)
38 (33 – 45)4/25 (16%)
362 (141–592)6.33 (5.24-6.89)
39 (34 – 43)1/19 (5%)
250 (157–555)6.26(5.36-6.86)
0.7410.3700.6550.790
Characteristic HIV• Use of HAART• HIV-RNA < LOD• HIV-RNA (cop/ml, log10)• CD4 cell-count (/µl)
14/25 (56%)14/24 (58%)
1.70(1.70 – 4.75)389 (335–612)
12/19 (63%)8/14 (57%)
2.29(1.70-4.53)452 (362–618)
0.7601.0000.8080.636
HCV-Treatment • delay treatment (weeks)• start within 12 weeks• start within 6 months• HCV-RNA neg. week 4• duration treatment (weeks)
19 (7 – 26)11/25 (44%)20/25 (80%)18/20 (90%)27 (23 – 47)
8 (3 – 18)13/19 (68%)18/19 (95%)7/24 (29%)
24 (14 – 33)
0.0810.1350.213
<0.0010.237
Vogel et al, EACS Madrid 2007Vogel et al, EACS Madrid 2007
Collaborative european study: 44 treated patients Collaborative european study: 44 treated patients
with SVR in 25/44 with SVR in 25/44 (57%)(57%)
Liver-related mortality in HIV: Mortavic 2005
24 000 patients in 2004, 19.4 % HCV co-infected, 313 deaths
AASLD 2007 – Rosenthal E, France, Abstract 135
HAART
8
91,6
1,56,9
2
84,5
6,68,8
1
48,7
36,7
1
4740,5
48,5
34,8
1,2
Overall Mortality
AIDS-relatedMortality
Liver-relatedMortality
Other
0
20
40
60
80
100
1995 1997 2001 2003 2005
12,616,714,3
• To diagnose
• To evaluate liver disease
• Adaptation of ARV
• HCV antiviral treatement
• To improve efficacy
Optimization of HCV treatment
HIV/HCV co-infection Evaluation of liver fibrosis
LB
Fibrotest
Liver stiffness
H. Fontaine et al (HAS). GCB 2007
FIB-4/Shasta/Fibrometre/Hepascore …
AST
ALTPlaquette xFIB-4 = AGE x
Années
UI / L
UI / L109 / L
Dynamics of liver fibrosis Unfair evaluation in F1+-F3-
0
5
10
15
20
25
30
Uni
tés
Colonne 2
F4
F3
F2
F1
F0
Graphe en boîtesEclaté par : Colonne 1
Aire de fibrose (%)
F0 F1 F2 F3 F4
A2-A3F2-F4
A0-A1F0-F1
Biopsy /3 yNIM/y
Antiviraltreatment
Biopsy and/or non invasive markers (NIM)
Evaluation
180 HIV-HCV
701 Alcohol
812 HBV
382 Hemochromatosis
2313 HCV
93 Steatosis BMI>25
200 PBC0.00
0.17
0.33
0.50
0.67
0.83
1.00
0 20 40 60 80
Haz
ard
func
tion
4682 patients
Poynard et al J Hepatol 2003;38: 257-65Age in years
Progression to cirrhosis
Main reasons to treat chronic HCV in HIV-infected patients
HIV patients live longer
Faster progression to liver cirrhosis
Increased mortality due to ESLD (end stage liver disease)
Higher risk of hepatotoxicity following treatment with ART drugs
19
SVR to IFN-RBV reduces liver-related complications in HIV/HCV coinfection GESIDA 3603 study cohort
• Determine effect of achieving SVR on mortality, liver-related morbidity, HIV progression
• 711 HIV/HCV+ pts from Spain, started IFN-RBV between Jan 2000 and Dec 2005
• SVR defined as undetectable serum HCV-RNA level 24 wks after discontinuation of therapy (achieved by 31% of pts)
• Analyses were adjusted for baseline liver fibrosis and benefit was highest in that group
Kaplan-Meier estimate of liver-related events stratified according to response to
IFN-RBV
Berenguer J, et al. 15th CROI, Boston 2008, #60
p<0.001 by log-rank test
100
80
60
40
20
0
4842363024181260Follow-up (months)
SVRNo SVR
Per
cen
tag
e
Case # 1
49-y-old patient with HIV/HCV coinfection• IVDU transmission risk factor for HIV and HCV, no
drug abuse more for >15 years• HAART since 2002 (lopinavir/r/[AZT/3TC])• HIV-RNA < 50 copies/ml for > 3 years• CD4-count 535 /µl, 26%• ALT 2-3 x ULN• HCV-RNA 4.600.000 IU, HCV GT 1a• Liver Fibroscan 60 KPa (F4-Fibrosis)• No clinical signs of advanced liver disease, but
decreased platelets of 70.000/µl
QuestionHow would you manage hepatitis C in this patient?
1. Cirrhosis and low platelets are contraindications for interferon therapy; therefore no HCV therapy (yellow)
2. Start with PEG-IFN/RBV (green)3. First optimize HAART and switch [AZT/3TC]
to different NUC-backbone (blue)4. Prepare patient for liver transplantation (red)
Zidovudine: impact on HCV treatment
HB decrease by week 4
3,14
1,96
0
1
2
3
ZDV No ZDV
HB
loss
(g/d
l)
RBV dose reduction by week 4
52%
20%
0%
20%
40%
60%
ZDV No ZDVPat
ient
s w
ith R
BV
dec
reas
e
Alvarez D et al. 12th Conference on Retroviruses and Opportunistic Infections (Abstract #: P-192). Boston, MA USA, February 22–25, 2005
PRESCO trial: design
Wochen
0 96724824 60 84
PE
GA
SY
S® 1
80 µ
g p
lus
CO
PE
GU
S®
1000
–120
0 m
g
12 36
Follow-up
G2,3
G1,4
G1,4
G2,3
Follow-up
Follow-up
Follow-up
Patients achieving an EVR (>2 log10 decrease in HCV RNA at week 12) continue their treatment
n=398
n=192
n=45
n=96
n=56
Ribavirin-Dosis in Genotype 1 - EVR:APRICOT (800 mg) vs PRESCO (1000 –1200 mg)
Ramos B, et al. J Viral Hepatitis 2007
HC
V R
NA
Ab
fall
(%
Pat
ien
ten
)
PRESCO (n=94)
APRICOT (n=176)
>2 log>1 log
Week 12On-treatment Analysis
Negative (<50 IU/mL)
34%
63%
84%
60%
78%83%
0
10
20
30
40
50
60
70
80
90
EOT and SVR Rate in PRESCO
010203040506070
8090
100
Total GT 1 GT 2/3 GT 4
EOT
SVR
90 %
50 %
67 %
41 %
72 %
33 %
55 %
36 %
262 193n=389
106 68n=191
137 110n=152
19 15n=46
Nunez M et al., AIDS Res Hum Retroviruses 2007
Case # 1 Patient is switched from [AZT/3TC] +
lopinavir/r to tenofovir/FTC + lopinavir/r; after 3 months of therapy and continued successful therapy with HIV-RNA < 50 copies/ml,HCV-therapy is initiated with PEG-IFN and ribavirin 1200mg weight adapted
After 12 weeks of HCV-therapy HCV viral load has dropped to 2000 IU; In parallel CD4-count has decreased to 160/µl (27%)
Question
How would you continue to manage this patient?
1. Stop HCV therapy (yellow)
2. Continue therapy (red)
3. Consider PEG-IFN dose reduction (blue)
04/18/23
Median Change from Baselinein CD4+ Counts*
-160-140-120-100-80-60-40-20
0204060
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76
IFN alfa-2a 3 MIU + RBV 800 mg (n = 174)PEG-IFN alfa-2a (40 kDa) 180 ug + Placebo (n = 196)PEG-IFN alfa-2a (40 kDa) 180 ug + RBV 800 mg (n = 217)
Med
ian
Ch
ang
e fr
om
Bas
elin
eM
edia
n C
han
ge
fro
m B
asel
ine
in C
D4
in C
D4++
Co
un
t (c
ells
/ C
ou
nt
(cel
ls/
L)
L)
Time (Weeks)Time (Weeks)* Patients receiving 48 weeks of treatment* Patients receiving 48 weeks of treatment
BL
Torriani F et al., N Eng J Med 2004
Mean Change from Baseline in HIV RNA: Patients with Detectable HIV
RNA at Baseline*
-2,0
-1,5
-1,0
-0,5
0,0
0,5
1,0
1,5
2,0
4 8 12 24 36 48 52 60 72
IFN alfa-2a 3 MIU + RBV 800 mg (n = 64)PEG-IFN alfa-2a (40 kDa) 180 ug + Placebo (n = 78)PEG-IFN alfa-2a (40 kDa) 180 ug + RBV 800 mg (n = 89)
Ch
ang
e in
Lo
gC
han
ge
in L
og
1010 H
IV R
NA
HIV
RN
A
Time (Weeks)Time (Weeks)
BL
* Patients receiving 48 weeks of treatment* Patients receiving 48 weeks of treatmentTorriani F et al., N Eng J Med 2004
SVR-Raten in the PRESCO-trial
0
10
20
30
40
50
60
70
80
90
48 weeks 72 weeks 24 weeks 48 weeks
31%
53%
67%
82%
59/192 24/45 64/96 46/56
HCV GT 1/4 (n=237) HCV GT 2/3 (n=152)
% S
VR
Nunez M et al., ICAAC 2006
Discontinuations due to
Patient wish: 15 (8%) 36 (80%) 4 (4%) 9 (16%)
APRICOT Study: SVR Rates in relation to virological response
Genotype 1
RVR 13 %
completeEVR 22 %
partialEVR 26 %
no EVR40 %
Genotype 2/3
RVR 37 %
completeEVR 35 %
partialEVR 12 %
no EVR 17 %
Rodriguez-Torres M et al., CROI (2008), Poster 1073
SVR = 1 %
SVR = 17 %
SVR = 63 %
SVR = 82 % SVR = 6 %
SVR = 18 %
SVR = 70 %
SVR = 94 %
HIV Medicine 2008
Proposed optimal duration of HCV therapy in HCV/HIV-coinfected patients.
W4 W12 W24 W48 W72
HCV-RNAneg
HCV-RNApos
> 2 log dropin HCV-RNA
< 2 log dropin HCV-RNA
HCV-RNAneg
HCV-RNApos
G2/3
G1/4
Stop
Stop
G2/3
G1/4
24 weekstherapy *
48 weekstherapy
72 weekstherapy
* In patients with baseline low viral load and minimal liver fibrosis.
HIV Medicine 2008
Case 2 42-y-old hemophiliac with HIV/HCV coinfection
– HIV first diagnosed 01/95, CDC C3– CMV-Retinitis 2003– 08/07 HAART for 4 years with Abacavir/3TC/lopinavir/r– HIV-RNA <50 copies/ml– CD4 430/µl (27%)
Patient is referred to our HIV-Hepatitis Clinic for further workup HCV-RNA 1.093.527 IU/ml; GT 3 infection Fibroscan 10.2 KPa F2-F3 Fibrosis
Question
How would you manage this patient?
1. Start PEG-IFN/RBV therapy for 48 weeks (yellow)
2. Switch Abacavir/3TC to Tenofovir/FTC and then start HCV-therapy (green)
3. Start PEG-IFN/RBV therapy for 24 weeks (blue)
4. Would not treat this patient for HCV at all (red)
Ribavirin in HIV/HCV Co-infection
Dose-dependent hemolytic anemia: mean 2.5 - 3 g/dL Hb < 4 wks
Drug-drug interactions• Anti-HIV antagonism with pyrimidine nucleoside analogs - AZT, D4T, DDC (in
vitro)1
• Inhibits intracellular phosphorylation
• Increased intracellular levels of DDI metabolites (in vitro); increased risk for lactic acidosis
• Recent data suggests decreased SVR under abacavir treatment; caveat abacavir treated patients had more fibrosis upon baseline and were more HAART experienced2,3,4
1) Vogt MW. Science 1987;235:1376, Baba AAC 1987;31:16132) Margt NA and Miller MD, 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris 2003; P9803) RIBAVIC Subanalyses CROI 2007; 4) CROI 2008
37
Effect of ABC on SVR rates in HCV patients treated with RBV• Proposed intracellular competition
between ABC and RBC (guanosine analogs)
• Retrospective study of 256 HIV/HCV pts on HAART starting peg-IFN + RBV1
– Differences between NRTI combinations mainly observed in subjects receiving lower RBV doses and in those needing higher RBV doses (GT 1 pts)
– Use of TDF/3TC was associated with improved SVR
• No difference in SVR with regard to NRTI choice (TDF vs ABC)2
1 Mira J, et al. 15th CROI, Boston 2008, #1074; 2 Moreno A, et al. ibid, #1075
p=0.02
p=0.01
0
10
20
30
40
50
60
ITT analysis Per-protocol analysis
ABC+ 3TC
TDF+ 3TC or FTC
n = 70 186 n = 57 160
SV
R (
%)
Response by NRTI group1
29
45
33
52
38
• Negative impact of abacavir at W4, W12, W48 & W72 is significant only when ribavirine levels are < 2.2 μg/ml, suggesting a putative interaction between ribavirin and abacavir
Rel
apse
rs (
%)
0
20
40
60
80
100
RBV > 2.2 μg/ml
p = 0.44 p = 0.08
RBV < 2.2 μg/ml
Relapse rate according to abacavir and ribavirin levelsRelapse rate according to abacavir and ribavirin levels
AASLD 2007 – Barreiro P et al.Abstract 342
Number of patients
55 27
with ABC
without ABC
Negative impact of abacavir on SVR (2)
Ribavirin monitoring (1)
• 22 HIV/HCV co-infected patients treated by PEG-IFN 2a 180 ug/sem + ribavirin 800-1 200 mg/d
– Genotype 1 : n = 10 ; 3 : n = 8
– 50 % with F > 2
– HCV RNA = 6 log10 copies/ml
• Measure of plasmatic (Cp) and erythrocyte (Ce) ribavirin levels (= 12 h after) at W4 and W12 :
– Significant correlation between Cp and Ce
– Correlation between Cp, Ce and hemoglobin decline
CROI 2007, Dominguez S et al. abst 893
Correlation between Cp, Ce at W4 and EVR
– Cut off Cp = 1,6 mg/l (génotypes 1,4)
– Cut off Ce = 140 mg/l
Non responders Responders1
1,4
1,2
1,6
1,8
2
2,2
2,4
RBV-P Cmin (mg.l-1)
20
60
100
140
180
220
Non responders Responders
RBV-E Cmin (mg.l-1)
CROI 2007, Dominguez S et al. abst 893
Ribavirin monitoring (2)
41
Case 3• 35-y-old female patient with HIV/HCV coinfection
– HIV first diagnosed 01/08, CDC B2– HIV-RNA 11.763 copies/ml– CD4 311/µl (23%)– No HAART
• Patient is referred to our HIV-Hepatitis Clinic for further workup
• Liver enzymes are slightly elevated (Grade 1)
• HCV-RNA 943.527 IU/ml; GT 3 infection
• Fibroscan 8.2 KPa F2 Fibrosis
42
Question• How would you manage this patient?
1. Start PEG-IFN/RBV therapy for 48 weeks (yellow)
2. Start HAART first and then treat HCV-infection (green)
3. Would not treat this patient for HCV at all (blue)
4. Something different (red)
Rate of SVR increases with higher CD4 %: APRICOT
Opravil et al. J AIDS 2008
3336
41
47
33
16
29
34
27
62
47
73
69
All patients(n=242)
HCV genotype 1(n=150)
HCV genotypes 2-3(n=78)
CD4%Min – Q1
Q1 – Med
Med – Q3
Q3 – Max
SV
R r
ates
Use of ARV in co-infected patients treated for HCV (1)
• Use of ARV :– Cautious use of nevirapine (AII)
– Same recommendations for initiation of ARV in co-infected patients than in HIV mono-infected (BII)
– If CD4 count at the limit of the recommended level ARV are prioritary (BIII)
– Avoid severe immune status (CD4 < 200/mm3) in co-infected patients (BII)
Alberti et al. ECC. J Hepatol 2006
Use of ARV in co-infected patients treated for HCV (2)
• ddI – Contra-indicated if cirrhosis (EI)– To avoid in patients with less severe liver disease (EII)
Alberti et al. ECC. J Hepatol 2006
A) Overall-Mortality
Observation time[days]500040003000200010000
Cu
mu
lati
ve s
urv
ival 1,1
,9
,7
,5
,3
P<0.0001
Patients with HAART
Patients with ART untreated Patients
6000
Patients under observation:HAART-group:93 79 33 - - - ART-group: 55 46 30 15 9 1Untreated-group: 137 94 49 37 32 27
6000500040003000200010000
1,1
,9
,7
,5
,3
A) Liver-related-Mortality
P<0.018
Patients with HAART
Patients with ART untreated Patients
Kaplan Meier Analysis of Overall and Liver-related Mortality
Qurishi N et al., Lancet 2003:362:1708-1713
Cu
mu
lati
ve s
urv
ival
Observation time[days]
Patients under observation:HAART-group:93 79 33 - - - ART-group: 55 46 30 15 9 1Untreated-group: 137 94 49 37 32 27
Pineda JA et al., Hepatology 2007;46:622-630
Probability of remaining free of developing a hepatic decompensation
Interventions for HCV/HIV-coinfected non-responders/relapsers to prior interferon-based therapies
• Wait until new antivirals come to the market in the rest
Virological failure
Optimal support (psychiatric, pharmacists, use of hematopoietic growth factors)
Limiting toxicities & poor adherence
Re-treatment using combination therapy with peginterferon plus weight-based ribavirin doses
Suboptimal prior treatment schedules:• Interferon (monotherapy or with ribavirin)• Low ribavirin doses• Short length of therapy
Recommended interventionCategory
Soriano V, Puoti M, Sulkowski M, Cargnel, Benhamou Y, Peters M, Mauss S, Brau N, Hatzakis A, Pol S, Rockstroh J. AIDS 2007
49
Sustained long-term antiviral maintenance with peg-IFN in HCV/HIV coinfected patients (SLAM-C)
Sherman K, et al. 15th CROI, Boston 2008, #59
Study design: ACTG 5178
• Lack of fibrotic progression in observation arm precludes ability to find efficacy in maintenance therapy
*NR, non-response
peg-IFN +Wt-based
RBV
peg-IFNmaintenance
Untreatedcontrols12 wks 6 wks
Liverbiopsy
72 wks
NR*
Liverbiopsy
Liverbiopsy
6543210-1-2-3-4-5-6
peg-IFN ObservationA
bso
lute
ch
ang
e in
Met
avir
Fib
rosi
s S
co
re
Treatment arm
n=24 n=21
Fibrosis change: Paired sample analysis
Liver transplantation
Duclos-Vallée J.C , EASL 2007, A 154
• Suivi de 99 patients VIH-VHC et VIH-VHB après leur première consultation dans un centre de transplantation entre décembre 1999 et septembre 2006
– VIH-VHC (n = 75), VIH-VHB (n = 8), VIH-VHB-VHC (n = 8), hépatite fulminante (n = 3), HNR (n = 3), autre cirrhose (n = 2)
Survie après la première consultation (n = 72)Survie après la première consultation (n = 72)
00
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
Années
Sur
vie
(%)
73 %
61 % 61 %
34 %
00
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
Années
Sur
vie
(%)
87 %79 % 79 %
44 %
25 %Transplantation hépatique
(n = 56)
Décès avant TH (n = 16)
Survival of co-infected after liver transplantation
• 51 patients co-infectés VIH-VHC suivis dans 14 centres et transplantés en 2002-2005 (75 % d’hommes, 14 % AgHBs+, 16 % avec HCC)
• Comparés à 1 177 patients mono-infectés VHC greffés dans la même période
• Critères sélection pour transplantation :– Pas d’antécédent d’affection classante SIDA– CD4 >100/mm3
– ARN VIH indétectable ou possibilité d’indétectabilité
• Résultats/commentaires– Survie à 3 ans comparable entre patients VIH+
et VIH- (mais suivi médian 1,4 an)– Résultats meilleurs que dans les autres séries
européennes (France, Royaume Uni)
VIH+ VIH-
1 an 82 % 78 %
2 ans 72 % 71 %
3 ans 61 % 65 %
Miro JM et al., ICAAC 2007, A H1732
Survie greffons
Survie patients
VIH+ VIH-
1 an 88 % 81%
2 ans 75 % 74 %
3 ans 64 % 69 %
Summary Chronic hepatitis C can be found in 30% of all HIV-
patients HCV/HIV coinfected patients show a faster progression
to cirrhosis and increased liver-related mortality With availability of pegylated interferon Hepatitis C
specific treatment options should be considered before onset of immunodeficiency in HIV-coinfected patients
HAART should not be withheld in coinfected patients
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