Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Pablo Barreiro, Fernanda Rick, Pablo Labarga, Eugenia Vispo,

José Vicente Fernández, Luz Martín-Carbonero and Vincent Soriano

Department of Infectious Diseases. Hospital Carlos III, Madrid

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Non Progression of LF after SVR

160 120 80 40 0

1,2

1,0

,8

,6

,4

,2

0,0

- ,2

Time (months)

OR 3.94 (95% CI, 1.39 - 11.11) [p=0.01]

SVR

non-SVR

Risk for developing

METAVIR F3-F4 scores

n=69

n=34

Barreiro et al. AVT 2006

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Regression of LF after SVR?

160 120 80 40 0

50

40

30

20

10

0

Time (months)

rho : 0.25 (95% CI, 0.04 – 0.96) [p=0.03]

rho : - 0.39 ( - 0.64 – - 0.06) [p=0.02]

160 120 80 40 0

50

40

30

20

10

0

Time (months)

rho : 0.25 (95% CI, 0.04 – 0.96) [p=0.03]

rho : - 0.39 ( - 0.64 – - 0.06) [p=0.02]

non-SVR

SVR

Median liver stiffness (Kpa)

n=69

n=34

Barreiro et al. AVT 2006

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Material and Methods HIV-HCV coinfected patients

Completed first-line pegIFN-RBV therapy

Two FibroScan exams:

First: <6 months prior to hepatitis C therapy

Second: >12 months after EOT

No alcohol abuse

HBsAg negative

CD4 counts >200 cells/uL

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Main Baseline Characteristics All SVR Non SVR p-value

N of patients (%) 113 57 (50) 56 (50)

Males (%) 85 (75) 42 (74) 42 (75) 0.9

Mean age (years) 42±5 42±5 43±4 0.9

Alcohol abuse (%) 4 (3.5) 2 (3.5) 2 (3.6) 0.9

Mean CD4 count (cells/uL) 562±303 537±247 589±354 0.4

HIV-RNA <50 copies/mL (%) 93 (81) 51 (89) 43 (77) 0.07

Under HAART (%) 101 (88) 54 (95) 46 (84) 0.06

Mean ALT (IU/L) 88±62 96±62 81±61 0.3

HCV-RNA >600,000 IU/mL (%) 95 (83) 41 (72) 52 (93) 0.004

HCV genotype 1-4 (%) 84 (73) 33 (58) 50 (89) <0.001

IL28B CC (%) 51 (44) 35 (61) 15 (27) <0.001

Mean liver stiffness (kPa) 10.5±6.7 10.7±8.3 10.2±4.6 0.7

Mean follow-up (years) 4.03±1.33 3.77±1.39 4.29±1.21 0.03

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Baseline Extent of Liver Fibrosis

0

10

20

30

40

50

60

70

F02 F3 F4

All

SVR

no SVR% o

f patients

57 59

55

26 25 27

17 16 18

<9.5 kPa 9.5-14.5 kPa >14.5 kPa

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Evolution of Liver Fibrosis in Non-SVR Patients

Baseline

End of follow-up

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Evolution of Liver Fibrosis in SVR Patients

Baseline

End of follow-up

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Qualitative Outcome of Liver Fibrosis by Treatment Response

35

14

6366

2

20

0

10

20

30

40

50

60

70

Better Similar Worse

SVR

Non-SVR

p=0.01

p=0.002

Evolution of LF at the end of follow-up

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

-4.0

-2.0

0.0

Δ o

f kP

a p

er

year

after

pegIF

N-R

BV

+0.93

-1.14

p<0.001

SVR Non SVR

Fibrosis Progression Rate (mean ΔkPa per year after hepatitis C treatment)

2.0

4.0

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

F02 F3 F4

Δ o

f kP

a p

er

year

after

pegIF

N-R

BV

Metavir at Baseline

p=0.05 p=0.01

-1.40

+1.57

+2.27

-3.68

-0.35

+0.18

p=0.02

Non-SVR

SVR

-8.0

-6.0

-4.0

-2.0

0.0

2.0

4.0

6.0

8.0

Fibrosis Progression Rate (mean ΔkPa per year after hepatitis C treatment)

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Fibrosis Progression Rate Δ

of

kP

a p

er

yea

r afte

r pe

gIF

N-R

BV

-10

0

10

20

0 5 10 15 20 25 30

Liver Stiffness at Baseline (kPa)

Non-SVR

SVR

Spearman´s Rho: 0.009 (p=0.97)

Spearman´s Rho: -0.79 (p<0.001)

o

x

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Multivariable Analysis

β (95% CI) p-value

Age (per year) 0.134 (-0.003 — 0.016) 0.15

Male gender -0.101 (-0.167 — 0.049) 0.28

HCV-RNA level (per log IU/mL) 0.028 (-0.045 — 0.061) 0.77

HCV genotype 1-4 -0.050 (-0.146 — 0.89) 0.63

HIV-RNA <50 copies/mL 0.032 (-0.125 — 0.166) 0.78

Under HAART 0.039 (-0.147 — 0.210) 0.73

IL28B CC vs non-CC -0.002 (-0.102 — 0.100) 0.98

F4 at baseline -0.112 (-0.201 — 0.049) 0.23

SVR -0.387 (-0.306 — -0.083) 0.001

Linear Regression for FPR

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Conclusions In HIV-HCV coinfected patients treated with pegIFN-

RBV

Liver fibrosis progresses if SVR is not attained

Liver fibrosis regresses if SVR is attained

The degree of liver improvement after SVR is greater in

patients with more advanced liver damage as assessed

by FibroScan:

True regression of more advanced fibrosis?

Early reduction of more intense liver inflammation?

Presented at the 7th International Workshop on HIV & Hepatitis Co-infection, Milan, Italy, 1 - 3 June 2011

Acknowledgements