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