current treatment of hepatitis c in hiv co infected patients l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Current treatment of hepatitis C in HIV co-infected patients PowerPoint Presentation
Download Presentation
Current treatment of hepatitis C in HIV co-infected patients

Loading in 2 Seconds...

play fullscreen
1 / 40

Current treatment of hepatitis C in HIV co-infected patients - PowerPoint PPT Presentation


  • 277 Views
  • Uploaded on

Current treatment of hepatitis C in HIV co-infected patients. Dominique SALMON. Internal Medicine Department, COCHIN Hospital Paris, FRANCE. 12th ISVHLD - ANRS Co-infection day, July 5, 2006. Main points. Chronic HCV infection Candidates Pre therapeutic assessement

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Current treatment of hepatitis C in HIV co-infected patients' - Sophia


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
current treatment of hepatitis c in hiv co infected patients

Current treatment of hepatitis C in HIV co-infected patients

Dominique SALMON

Internal Medicine Department, COCHIN Hospital

Paris, FRANCE

12th ISVHLD - ANRS Co-infection day, July 5, 2006

main points
Main points

Chronic HCV infection

Candidates

Pre therapeutic assessement

Peg IFN and RBV doses

Treatment duration

Management of adverse events

Acute HCV infection

slide3
Candidates and

Pretherapeutic assessement

candidates to therapy
Candidates to therapy
  • All HCV chronically infected patients should be offered treatment if the benefits outweigh the risks
  • CD4 < 200/mm3 : treat HIV first
  • Alcoholics : - same efficacy of PegIFN + RBV

- Pb of adherence to treatment

  • Active drug users: - opiate substitution priority

- case by case evaluation

Alberti et al, 1st ECC, J Hepatol 2005

pretherapeutic liver evaluation
Pretherapeutic liver evaluation
  • HCV genotype
  • HCV viral load
  • Liver biopsy: useful, but not mandatory when a decision to treat has been taken
  • New markers of fibrosis
impact of genotype and hcv rna on svr
Impact of genotype and HCV-RNA on SVR

% pts with SVR in APRICOT

70

> 5,9 log

60

UI/ml

< 5,9 log

50

UI/ml

40

30

20

10

0

geno 1

geno 2-3

Torriani et al NEJM 2004,

liver biopsy in hiv hcv co infected patients
Liver biopsy in HIV/HCV co-infected patients

Not required for treatment decision

Required for treatment decision

  • Genotype 2 and 3
  • Genotype 1 and 4 , and

low HCV load (≤800,000

IU/ml)

  • Genotype 1 and 4, and high

HCV load (>800,000 IU/ml)

  • Presence of co-morbidities :

- Excessive alcohol

consumption

- HBV and/or delta co-infection

- Medication hepatotoxicity

Alberti et al, 1st ECC, J Hepatol 2005

new tests of fibrosis

Concordance

Discordance

Minimal fibrosis < F2

Moderate or severe fibrosis F >2

Liver biopsy

Treatment or

follow-up

Follow-up

Treatment

New tests of fibrosis

FibroScan

+ seric markers

Castera et al. Gastroenterology 2005; 128: 343-50.

slide10

Doses of Peg-IFNa

  • Peg-IFNa 2a 180 mg/w
  • Peg-IFNa 2b 1.5 mg/kg/w

100

80

60

44

SVR (%)

40

40

27

27

20

0

APRICOT

ACTG 5071

RIBAVIC

LAGUNO

Peg-IFN 2a

Peg-IFN 2b

svr with pegifn rbv in hiv hcv patients
SVR with PegIFN + RBV in HIV/HCV patients

APRICOT

ACTG5071

RIBAVIC

LAGUNO

Gobal

40%

27%

27%

44%

Genotype 2-3

62%

44%

27%

53%

Genotype 1

29%

17%

(1 and 4)

14%

38%

(1 and 4)

dose of ribavirin is critical
Dose of ribavirin is critical

Genotype 1 or 4

Genotype 2 or 3

Low ARN HCV

< 800 000 UI/ml

High ARN HCV

> 800 000 UI/ml

Ribavirin 800 mg

Ribavirin 1000-1200 mg

Alberti et al, 1st ECC, J Hepatol 2005

dose of ribavirinin 2006
Dose of ribavirinin 2006

Genotype 1 or 4

Genotype 2 or 3

Whatever

HIV-RNA

Ribavirin 800 mg

Ribavirin 1000-1200 mg

Alberti et al, 1st ECC, J Hepatol 2005

slide14

Increased ribavirine dose useful in genotype 1 with high viral load (WIN-R)

Group A: PEG-IFNα-2b + ribavirin 800 mg/d

vs.

Group B: PEG-IFNα-2b. + ribavirin 13 + 2 mg/kg

G1: 48 week G2-3 : 24 sem. vs. 48 week

Genotype 1

Genotype 2, 3

p = 0.173

p = 0.047

39

68

40

65

34

60

32

58

27

70

30

SVR (%)

20

SVR (%)

n=

10

n=

725

776

446

391

322

316

588

602

0

0

Viral load> 600 000 Ul/ml

Viral load < 600 000 Ul/ml

24 weeks

48 weeks

Jacobson et al. LB3, AASLD 2005

presco trial
PRESCO trial

G1,4

Follow-up

G1,4

Follow-up

Peg-IFN + RBV 1000-1200 mg/day

n=389

G2,3

Follow-up

G2,3

Follow-up

84

72

60

48

96

24

36

12

0

Study weeks

Only patients who achieved EVR (>2 log drop in HCV-RNA at week 12) continued treatment.

apricot 800mg d vs presco and fried 1000 1200 mg d genotype 1 response
APRICOT (800mg/d) vs PRESCO and FRIED (1000-1200 mg/d) : genotype 1 response

100

%

90

%

80

%

70

%

46%

60

%

Percentage of patients

Apricot

34%

36%

50

%

Presco

31%

29%

40

%

Fried

30

%

13%

20

%

10

%

0

%

<

50

UI

/

ml W

4

SVR

On-treatment analysis

Soriano, ICAAC 2006, accepted

relation between rbv concentration and sustained virologic response in co infected patients
Relation between RBV concentration and sustained virologic response in Co-infected patients

3,5

D4

W2

W3

3

Virologic failure

Virologic succes

2,5

2

RBV Concentration (mg/L)

1,5

1

0,5

0

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Time (hours)

Breilh D., Abstract 928, CROI 2005

positive predictive value of early virological response evr on svr
Positive predictive value of early virological response (EVR) on SVR

All genotypes

Genotype 1

Genotype 2/3

EVR at W12

> 2 log drop HCV RNA

56 %

45 %

70 %

EVR at W4

> 2 log drop HCV RNA

undetectable

HCV-RNA

66 %

83%

58 %

82%

74 %

94%

Torriani, NEJM, 2004, 292;

probability of success is evaluable as early as w4
Probability of success is evaluable as early as W4

SVR probability

83%

HCV-RNA

undetectable

geno 1

58%

  >2 log HCV-RNA

decrease

SVR probability

60%

geno 2/3

74%

negative predictive value of early virological response evr
Negative predictive value of early virological response (EVR)

All genotypes

Genotype 1

Genotype 2/3

No EVR at W12

< 2 log drop HCV RNA

-

98 %

100 %

No EVR at W4

< 2 log drop HCV RNA

88 %

90 %

84 %

Torriani, NEJM, 2004, 292;

slide22

Early viral Kinetics in RIBAVIC trial

VPP

VPN

99

100

94

82

80

71

60

40

20

0

W4

W12

Carrat et al. JAMA 2004

duration of treatment
Duration of treatment

Evaluate at week 12

early virological response

HCV-RNA

 > 2 log

HCV-RNA 

< 2 log

TTT should be

stopped

Treatment

for 48 weeks

If HCV-RNA neg at W24

Alberti et al, 1st ECC, J Hepatol 2005

keep patients on the optimal dose of peg ifn and ribavirin
Keep patients on the optimal dose of peg-IFN and ribavirin

Apricot

Ribavic

ACTG

5071

Laguno

  • dose

AE

Lab abnormality

25%

18%

16%

20%

pegIFN RBV

10% 25%

34% 18%

31%

Tx interruption

25%

39%

31%

23%

Proactive management of adverse events and antiretroviral treatment

Torriani NEJM 2004;Carrat Jama 2004; Chung,NEJM 2004; Laguno AIDS 2004

slide27

Impact of adherence on SVR with

PegIFNa 2a/ribavirinbitherapy

SVR depends on RBV doses within the 12 first weeks

70

60

66

p=0.01

50

57

40

45

30

20

10

0

0

>

97

%

80

-

97

%

60

-

80

%

<

60

%

Reddy et al. EASL 2005

prevention and proactive management of adverse events
Prevention and proactive management of adverse events

Influenza-like syndrome

paracetamol

+/- NSAID

Depression

Manage depressive mood changes

Anemia

Hb < 8 g/dl : 3.8%

Neutropenia

avoid AZT

Use EPO

Use G-CSF

Mitochondrial toxicity (1-3%) Liver decompensation

No ddI (d4t) : RR X 2.3

Hyper or hyothyroidism

betablockers

levothyroxin

keep > 95% of the dose mainly for the first 3 months

ribavic mitochondrial toxicity pancreatitis hyperlactatemia
RIBAVIC – Mitochondrial toxicity (pancreatitis –hyperlactatemia)
  • Incidence
    • 27,5 / 1000 pat./year (all)
    • 34,1 / 1000 pat./year (with ARV)
    • 0 / 1000 pat./year (without ARV)

ddI

d4T

% with mitochondrial toxicity

Yes

Yes

24 %

Yes

No

7 %

No

Yes

0 %

Non

No

2 %

Multivariate analysis : odds-ratio for ddI = 23 [95 % CI : 5-105]

Carrat et al. JAMA 2004; 292: 2839-2848

azt impact on anemia and rbv doses
AZT: impact on anemia and RBV doses

Hb decrease at W4

RBV dose decrease at W4

3,14

60 %

52 %

3

1,96

40 %

2

Patients with RBV dose decrease

Hb (g/dl)

20 %

1

20 %

0

0 %

AZT

No AZT

AZT

No AZT

Alvarez D et al. 12th Conference on Retroviruses and Opportunistic Infections (Abstract #: P-192). Boston, MA USA, February 22–25, 2005

impact of epoetin alfa
Impact of Epoetin alfa

40

Epoetin alfa

/

Epoetin alfa

35

Placebo

§

/

Epoetin alfa

30

25

%

25

23

%

22

%

20

*

% Change from Study Entry

14

%

15

12

%

11

%

9

%

9

%

10

8

%

6

%

5

%

5

0

-

1

%

-

5

Week

9

Week

17

Week

9

Week

17

Week

9

Week

17

Physical

Mental

Vitality

*p = 0,009 ; †p < 0,001 ; ‡p < 0,03 ; §p = 0,003 ; Epoetin alfa vs. Placebo.

Afdhal et al. Gastroenterology 2004

management of non responders
Management of non responders

Was the treatment adequate ?

No

Adherence Pb,

side effects,

low doses

Yes

100% of the dose

during the first 12 W

Partial response

or relapse

No response

= true

non responder

Retreatment

approach dependent on histology
Approach dependent on histology :
  • Minimal disease => wait new drugs
  • Significant disease (F3-F4) =>
    • Monitor ESLD and HCC
    • Consider alternative strategies

Maintenance

therapy

Retreatment

High dose peg-IFN?

New drugs ?

HAART

treatment of acute hcv hepatitis
Treatment of acute HCV hepatitis
  • 168 HCV monoinfected: ALT (5-10x), PCR and/or sero-conversion
  • Egypt, USA, Germany
  • Geno 1, 4: 60%
  • 1.5mg/kg/wk PEG 2b for 12 weeks
  • Initiation from 1st positive RNA result either at :

SVR (%)

Time of Rx onset Intent to Rx Treated

8 weeks (n=43) 95% 95%

12 weeks (n=43) 93% 91%

20 weeks (n=82) 77% 70%

  • Kamal et al Gastroenterology 2006;130:632-8
slide36

Treatment of acute HCV

Geno 1 Geno 2+3 Geno 4

  • Kamal et al Gastroenterology 2006;130:632-8
comparison of the 2 largest studies of acute hcv infection
Comparison of the 2 largest studies of acute HCV infection

Kamal et alWiegard et al

N° patients 168 89

Rx duration 12 weeks 24 weeks

SVR 95% (early Rx) 89%

Main group Occ exposure: 56% IDU, sex: 44%

+ve factors Geno non-1 ALT >500

  • PEG alone 12 weeks as good as 24 weeks
  • Delay up to 12 weeks max from diagnosis
  • Max chance of SVR for geno 2 or 3
  • Kamal et al Gastroenterology 2006;130:632-8; Wiegand et al Hepatology 2006; 43: 250-6
treatment of acute hcv hepatitis in hiv infection
Treatment of acute HCV hepatitis in HIV infection

Initiation from PCR/seroconversion at 12 weeks

Vogel et al, J Viral Hepatitis, 2005; Gilleece et al, J AIDS 2005;Dominguez S et al, submitted

conclusion 1
Conclusion (1)
  • As eradication is possible, hepatitis C treatment discussed for all patients, except if minimal liver disease
  • Histological evaluation crucial: liver biopsy should not be an obstacle new tools available.
  • Improved success rates with HCV therapy due to:
    • proactive management side effects
    • increased ribavirine dose (1000-1200mg genotype 1)
conclusion 2
Conclusion (2)
  • Duration of treatment (48 weeks) depends on EVR:
    • at 12 weeks : stop if no significant response
    • at 24 weeks : stop if viral load remains positive.
  • Fields of research :
    • Geno1, high VL : higher doses RBV and/or Peg IFNa ?
    • Slow responders : longer duration of therapy ?
    • True non responders: maintenance therapy ?
    • New molecules.