hcv in the hiv infected patient
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Slide 1
HCV in the HIV infected Patient
David L. Thomas, MD
Advisory Board – Merck & Co.
Slide 2
HCV Treatment Future is Bright
Slide 3
HCV Treatment Present is Challenging for HIV/HCV Coinfected Patients
Slide 4
2008 Management of HIV/HCV Coinfected Patients
• Whom to treat• How to treat• When to stop
Slide 5
56 year old Caucasian male with HIV and HCV infection
• HIV and HCV diagnoses early 1990s; exposures late 1970s
• No ART: CD4+ lymphocyte 782/mm3, HIV RNA <400c/ml
• HCV genotype 1a; HCV RNA 6.4 log IU/ml• ALT 77; INR 1, TB 1.9; creat 1; plts 219K • Liver biopsy 2001: mild fat; no fibrosis
Slide 6
Which would you do next?
A. Repeat liver biopsy B. Check FibroSure C. Peg IFN and RBV, check HCV RNA 4 and
12 wksD. Compliment him on his DNA and followE. Check CD4+ lymphocyte percent
Slide 7
Which would you do next?
Repeat liver biopsy A. Could be progressionB. Could be an error
Slide 8
Three Year Predictive Value of Liver Biopsy Represents Error and Natural History
• 175 HIV/HCV coinfected persons biopsied twice, median 2.9 yrs
• 41 (24%) had ≥ 2pt increase
• Must repeat test 1
8 2 1
45 20 11 8
20 12 2 3
12 7 5 2
2 2 2
2 1
3 2
1
-3
-2
-1
0
1
2
3
4
5
6
-1 0 1 2 3 4
Ishak Fibrosis Stage at Initial BiopsyC
hang
e in
Isha
k Fi
bros
is S
tage
Sulkowski et al AIDS 2007
Slide 9
Sampling error of liver biopsyFibrosis area: 65%
Fibrosis area: 15%Courtesy of M. Pinzani, Florence
Slide 10
Liver Biopsy Readings Have Limited Validity
Sampling error (metavir 2-4 fibrosis)• 161 > 3cm biopsies ‘reduced’ 1.5cm and
1cm and re-scored1
• % “mild”: 3cm 59%; 1.5 cm 68%; 1cm 80%• Specimen diameter reduced:
• 63% mild increased to 87%• sampling error underestimates
fibrosis
1 Colloredo J Hepatol 2003
Slide 11
Which would you do next?
Check FibroSure Reasonable validity in HIV/HCV coinfected persons, especially considering lack of sensitivity and specificity of biopsy
Slide 13
Which would you do next?
Peg IFN and RBV, check HCV RNA 4 and 12 wks
A. Liver disease staging is inaccurate B. Therapeutic trial provides information on
adverse events and response for this patient
Slide 14
FibroSure=0.9; repeat liver biopsy (>2 cm) shows metavir 3 (of 4) fibrosis; mild macro-vesicular fat, moderate activity. Now what?
A. Peg IFN and RBV B. Wait for new HCV drugs
C. AZT-based ARTD. ABC-based ARTE. TDF-based ART
Peg IFN and RBV after
Slide 15
HAART and Treatment of HCV
• ART should be given if indicated by HIV stage
• Insufficient evidence that PegIFN/RBV response is improved
By ART By higher CD4
• Many recommend it anyway, especially with high HIV RNA or CD4 350-500/mm3
Slide 16
NRTI Choice and RBV
• Don’t use ddI and RBV• Avoid AZT and RBV• ? ABC and RBV
1493 HIV/HCV coinfected getting PegRBV 62% No SVR: associated with GT 1/4; viral load;
low RBV trough; ABC (OR 2.22, 0.91-5.40) 2No difference in SVR in 238 TDF versus 52
ABC2
Effect: Bani Sadr J AIDS 2007; 1Vispo Antivir Ther 2008; Mira et al CROI 2008 ABST 1074; No effect: 2Gonzales-Garcia CROI 2008 ABST 1076
Slide 17
Peg and RBV 1.2 g/d was started without ART. Treatment is well tolerated. HCV RNA drops 6.4 to 4.99 log IU at 30 days. Which is best?
A. Stop, no chance of SVRB. Increase Peg dose C. Continue current therapyD. Start pioglitazoneE. Start ART
Slide 18
Baseline HCV RNA was retested with assay with high upper range=7.5 log IU/ml (vs 6.2). Treatment continued. HCV RNA drops to 3.7 log IU at 12 weeks. Which is best?
A. StopB. Reduce Peg IFN dose, stop RBV C. Continue current therapy
Slide 19
Treatment continued. HCV RNA drops to 3.42 log IU at 24 weeks. ALT 58. Which is best?
A. StopB. Reduce Peg IFN dose, stop RBV C. Continue current therapy for 18 monthsD. Stop, start pioglitazone and ART and
restart ART in 6 months
Slide 20
Forms of Virologic Response
1.00E+00
1.00E+01
1.00E+02
1.00E+03
1.00E+04
1.00E+05
1.00E+06
0 4 8 12 24 48 72
NonRapidEarlyIncomplete
Weeks of HCV Treatment
Log
IU H
CV
RN
A
PEG/RBV ~44%
Slide 21
HCV Therapy Generally Should be Stopped Unless >2 logs at 12 wks and undetectable at 24 wks
• No cure• No control
Slide 22
Rare SVR Without Early Virologic Response in HIV/HCV Coinfected Patients
Study Peg RBV Rx No EVR SVR
ACTG 5071 106 63 0
APRICOT 289 85 2
RIBAVIC 205 68 1
Chung NEJM 2004; Torriani NEJM 2004; Carrat JAMA 2004
Slide 23
No Control of HCV Infection in ACTG 5178 (SLAM C)
PegIFN 2a
RBV 1-1.2g/d
PegIFN 2a
OBSERVECONTINUE
RANDOMIZEEVR
_
+
72 Weeks
Bx1 Bx2 Bx3
Sherman and 5178 team CROI 2008
Slide 24
ACTG 5178 SLAM C EVR Was Common
PegIFN 2a
RBV 1-1.2g/d
PegIFN 2a
OBSERVECONTINUE
RANDOMIZEEVR
_
+
72 Weeks
Bx2 Bx3
329 295
112
44.4%
183
55.6%
Bx1
Sherman and 5178 team CROI 2008
Slide 25
ACTG 5178 SLAM C Maintenance Versus Observation
PegIFN 2a
RBV 1-1.2g/d
PegIFN 2a
OBSERVECONTINUE
RANDOMIZEEVR
_
+
72 Weeks
Bx2 Bx3
329 295
112
44.4%
183
55.6%
Bx1
44
42
Sherman and 5178 team CROI 2008
Slide 26
-6-5-4-3-2-10123456
Cha
nge
in m
etav
ir fib
rosi
s
PEG-IFN
N=24
Observe
N=21
• No benefit of 18 months of maintenance
• DSMB stopped study
• Cirrhosis 18% and 21% of maintenance and observation arms
Sherman and 5178 team CROI 2008
ACTG 5178 No Benefit of Maintenance
Slide 29
Treatment stopped. Creat 1.0; ALT 74 IU; INR 1.0; which is best?A. Refer to Dr. Sulkowski for investigational HCV
drug B. Refer to Dr. Fierer for counseling to prevent
secondary transmissionC. Refer to Dr. Afdhal for management of
cirrhosis and transplant evaluationD. All of the above
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