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Understanding Optimal Use and Interpretation of Assays in HCV
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Understanding the Optimal Use and Interpretation of Assays in HCV

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Faculty Affiliation and Disclosure

Paul Y. Kwo, MD
Professor of Medicine Medical Director of Transplantation Division of Medicine/Gastroenterology/Hepatology Indiana University School of Medicine Indianapolis, Indiana
Paul Y. Kwo, MD, has disclosed that he has received consulting

fees from Abbott, Anadys, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Johnson & Johnson, Merck, Novartis, and Vertex; has received fees for non-CME services from BristolMyers Squibb, Gilead Sciences, Merck, and Roche; and has contracted research with Abbott, Anadys, Bayer, Bristol-Myers Squibb, Conatus, GlaxoSmithKline, Merck, Novartis, Roche, and Vertex.
New Standard of Care for Patients With HCV

Patterns of Virologic Response

7 HCV RNA (log10 IU/mL)[1] 6 5 4 Partial response Relapse
40% chance of SVR with pegIFN/RBV[2] Undetectable
Null response
3
2 1 0 -8 -4 -2 0
RVR 4 8
EVR 12 16 20 24 32 40
EOT 48 52 60
SVR 72
Wks After Start of Therapy

1. Ghany MG, et al. Hepatology. 2009;49:1335-1374. 2. McHutchison JG, et al. N Engl J Med. 2009;361:580-593.

Addition of TVR or BOC to PegIFN/RBV Improves SVR in Genotype 1 Patients

HCV NS3/4A protease inhibitors BOC and TVR approved by FDA, May 2011[1,2]
Indicated in combination with pegIFN/RBV for treatment of genotype 1 HCVinfected patients who are previously untreated or who have failed previous therapy
100
69-83
80 SVR (%) 60 40 20 0 Treatment Naive[3,4] Relapsers[5,6] 38-44 24-29
63-75
PegIFN + RBV BOC/TVR + pegIFN + RBV 40-59 29-38
7-15
5 Partial Responders[5,6] Null Responders[6,7]
1. Boceprevir [package insert]. May 2011. 2. Telaprevir [package insert]. May 2011. 3. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 4. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 5. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 6. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 7. Vierling J, et al. AASLD 2011. Abstract 931.

Proper Use of HCV Assays Essential For Successful Management With HCV PIs
HCV RNA level important throughout treatment to determine
Eligibility for shortened therapy (response-guided therapy) Discontinuation of therapy due to futility
Minimizes risk of resistance and unnecessary adverse events
Assessment of EOT response Assessment of SVR
Additional genetic testing may help predict response to treatment
HCV RNA Assays in the Protease Inhibitor Era

Key Challenges Regarding Use of HCV RNA Assays in Protease Inhibitor Era
Package inserts for BOC and TVR specify different time points for monitoring HCV RNA
Available HCV RNA assays in practice have different quantifiable ranges
Different HCV RNA thresholds used for RGT determination vs SVR

Different HCV RNA thresholds used for defining treatment futility with BOC vs TVR

HCV RNA Assays: LLOD Is Distinct From LLOQ

LLOQ
Lowest HCV RNA concentration within linear range of assay
ie, smallest amount of HCV RNA that can be not only detected but also accurately quantified
LLOD
Lowest amount of HCV RNA concentration that can be detected with 95% probability to determine presence or absence

HCV RNA Levels and Relationship to LLOD and LLOQ

HCV Treatment
8
Log10 Viral Titer 6 4 2 1 0
Detectable/ quantifiable
Detectable/not quantifiable Not quantifiable/ not detectable
LLOQ LLOD
Time SVR
Adapted from Naeger LK, et al. Intl Workshop on Clinical Pharmacology of Hepatitis Therapy 2011. Abstract R-8.

FDA-Approved Qualitative HCV RNA Assays

Assay (Manufacturer ) Amplicor HCV v2.0 (Roche Molecular Systems) Cobas Amplicor HCV v2.0 (Roche Molecular Systems) Ampliscreen (Roche Molecular Systems) Versant HCV RNA Qualitative Assay (Siemens Healthcare Diagnostics) Procleix HIV-1/HCV Assay (Chiron Corporation) Method Manual RT-PCR Semiautomated RT-PCR Semiautomated RT-PCR LLOD, IU/mL 50 50 < 50 Setting Diagnosis and monitoring Diagnosis and monitoring Blood screening Diagnosis and monitoring Blood screening
Semiautomated TMA
10
Manual TMA
< 50
All assays report HCV RNA as detected/not detected

Ghany MG, et al. Hepatology. 2009;49:1355-1374.

Quantitative HCV RNA Assays

Assay (Manufacturer)[1] Amplicor HCV Monitor (Roche Molecular Systems) Cobas Amplicor HCV Monitor V2.0 (Roche Molecular Systems) Versant HCV RNA 3.0 Assay (bDNA) (Siemens Health Care Diagnostics) LCx HCV RNA-Quantitative Assay (Abbott Diagnostics) SuperQuant (National Genetics Institute) Cobas TaqMan HCV Test (Roche Molecular Systems) COBAS TaqMan HCV Test v2.0 for use with High Pure System (Roche Molecular Systems) Abbott RealTime HCV Assay (Abbott Diagnostics) Method Dynamic Range, IU/mL (LLOQ-ULOQ) 600-500,000 600-500,000 615-7,700,000 25-2,630,000 30-1,470,000 43-69,000,000 LLOD, IU/mL FDA Approved Manual RT-PCR Semiautomated RT-PCR Semiautomated bDNA signal amplification Semiautomated RT-PCR Semiautomated RT-PCR Semiautomated RT-PCR N/A 600 615 23 30 18 Yes Yes Yes No No Yes
Semiautomated RT-PCR
Semiautomated RT-PCR
25-300,000,000
15
Yes
12-100,000,000
12
Yes
Phase III registration trials for both BOC and TVR used COBAS TaqMan HCV Test v2.0 for use with High Pure System
1.3% false-positive rate[2]
1. Ghany MG, et al. Hepatology. 2009;49:1355-1374. 2. Naeger LK, et al. Intl Workshop on Clinical Pharmacology of Hepatitis Therapy 2011. Abstract R-8.

SVR Rate by HCV RNA Status (LLOQ vs LLOD) for BOC and TVR
SVR rate lower when HCV RNA not undetectable at key time points during therapy
BOC/PR RGT
100
80 SVR (%)
T12/PR
100
80 SVR (%)
Undetectable (Below LLOD) Detectable/Below LLOQ Above LLOQ (> 25 IU/mL)
60
40 20 0 4 6 8 10 12 16 20
60
40 20 0
10
12
16
20
Treatment Wk
Treatment Wk
Naeger LK, et al. Intl Workshop on Clinical Pharmacology of Hepatitis Therapy 2011. Abstract R-8.
Using HCV RNA Assays in Clinical Practice

Predictive Value of Baseline HCV RNA for Achieving SVR

100 78 75 SVR (%)
< 800,000 IU/mL 800,000 IU/mL

74 SVR (%)
100 85 75 63
800,000 IU/mL > 800,000 IU/mL

76
61
50
50
25 n/N = 0 64/ 82 207/ 281
25 n/N = 0 45/ 197/ 53 313 41/ 192/ 54 314
T12PR arm ADVANCE (TVR)[1]
BOC/PR48 BOC/PR RGT SPRINT-2 (BOC)[2]
1. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 2. Poordad F, et al. N Engl J Med. 2011;364:1195-1206.

Patients Responding Early Can Achieve High SVR Rates With Shortened Therapy
Response-guided therapy: patients who achieve optimal virologic response at early time points can receive abbreviated therapy without reducing their chance of SVR Patients eligible for RGT
Boceprevir: noncirrhotic treatment-naive patients, previous relapsers, and previous partial responders[1,2]
RGT criterion: Must achieve undetectable HCV RNA at Wk 8 (ie, Wk 4 of triple therapy) and maintain it at Wk 24
Telaprevir: noncirrhotic treatment-naive patients and previous relapsers*[2,3]

RGT criterion: Must achieve undetectable HCV RNA at Wk 4 of triple therapy and maintain it at Wk 12
*AASLD guidelines state that RGT may be considered with TVR in previous partial responders. 1. Boceprevir [package insert]. May 2011. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 3. Telaprevir [package insert]. May 2011.

Response-Guided Therapy Paradigm With BOC + PegIFN/RBV in Tx-Naive Patients

Indicated for all noncirrhotic treatment-naive patients
HCV RNA
Undetectable < 100 IU/mL PegIFN + RBV 0 4 8 Undetectable
BOC + PegIFN + RBV 12 24
Early response stop at Wk 28; f/u 24 wks 28 36 48
HCV RNA
Detectable < 100 IU/mL PegIFN + RBV 0 4 8 Undetectable Slow response extend triple therapy to Wk 36; PR to Wk 48; f/u 24 wks PegIFN + RBV 28 36 48
Boceprevir [package insert]. May 2011. Ghany MG, et al. Hepatology. 2011;54:1433-1444.

Response-Guided Therapy Paradigm With BOC + PegIFN/RBV in Tx-Exp Patients

Indicated for noncirrhotic previous relapsers or partial responders
HCV RNA
Undetectable < 100 IU/mL PegIFN + RBV 0 4 8 Undetectable Early response stop at Wk 36; f/u 24 wks 28 36 48
HCV RNA
Detectable < 100 IU/mL PegIFN + RBV 0 4 8 Undetectable Slow response PR to Wk 48; f/u 24 wks PegIFN + RBV 28 36 48
Boceprevir [package insert]. May 2011. Ghany MG, et al. Hepatology. 2011;54:1433-1444.

Response-Guided Therapy Paradigm With TVR + PegIFN/RBV in Tx-Naive Patients

Indicated for all noncirrhotic treatment-naive patients
HCV RNA
Undetectable Undetectable Undetectable
TVR + PegIFN + RBV 0 4 12
PegIFN + RBV
eRVR stop at Wk 24, f/u 24 wks 24 48
HCV RNA
Undetectable or Detectable detectable ( 1000 IU/mL) Undetectable ( 1000 IU/mL) No eRVR extend pegIFN + RBV to Wk 48; f/u 24 wks
TVR + PegIFN + RBV 0 4 12 24
PegIFN + RBV 48
Telaprevir [package insert]. May 2011. Ghany MG, et al. Hepatology. 2011;54:1433-1444.

Response-Guided Therapy Paradigm With TVR + PegIFN/RBV in Tx-Exp Patients

Same as naives; indicated for noncirrhotic previous relapsers[1]*
HCV RNA
Undetectable Undetectable Undetectable
TVR + PegIFN + RBV 0 4 12
PegIFN + RBV
eRVR stop at Wk 24, f/u 24 wks 24 48
HCV RNA
Detectable Undetectable/detectable ( 1000 IU/mL) ( 1000 IU/mL) Undetectable No eRVR extend pegIFN + RBV to Week 48; f/u 24 wks
TVR + PegIFN + RBV
PegIFN + RBV
0 4 12 24 48 [2] but package insert *AASLD guidelines say RGT may be considered for prior partial responders recommends 48 weeks of therapy[1] 1. Telaprevir [package insert]. May 2011. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.

HCV RNA Assay Characteristics for RGT With BOC or TVR

A quantitative assay with an LLOQ of 25 IU/mL and an LLOD of approximately 10-15 IU/mL must be used Confirmed detectable but below limit of quantification HCV RNA result should not be considered equivalent to an undetectable HCV RNA result
8
Log10 Viral Titer
6
4 2
Detectable/ quantifiable
Detectable/not quantifiable
LLOQ LLOD
1
Undetectable/not quantifiable
0 0
Time
Boceprevir [package insert]. May 2011. Telaprevir [package insert]. May 2011.

Predictive Value of Response to 4-Wk Lead-in Phase

1 log10 vs < 1 log10 decline in HCV RNA following 4-wk lead-in phase with pegIFN/RBV strongly predicts SVR in patients receiving BOC-based therapy
Treatment-naive patients[1]
OR: 9.0; P < .001
Treatment-experienced patients[2]
OR: 5.2; P < .001
1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Zeuzem S, et al. EASL 2011. Abstract 484.

Boceprevir Futility Rules: Wks 12 and 24 Key Time Points

Treatment-naive and treatment-experienced patients
PegIFN + RBV BOC + PegIFN + RBV BOC + PegIFN + RBV 8 Early response*; stop at Wk 28 or 36; f/u 24 wks F/u PegIFN + RBV 24 wks Wks
12
24
28
36
48
Stop all treatment if HCV RNA 100 IU/mL
Stop all treatment if HCV RNA detectable (> LLOD)
Use quantitative assay to determine if HCV RNA < or 100 IU/mL at Wk 12
Use assay with LLOD of 10-15 IU/mL to determine if HCV RNA detectable at Wk 24
*Undetectable HCV RNA at Wks 8 and 24 of therapy (Wk 4 of triple therapy). Boceprevir [package insert]. May 2011.

Telaprevir Futility Rules: Wks 4, 12, and 24 Key Time Points

Treatment-naive and treatment-experienced patients
TVR + PegIFN + RBV PegIFN + RBV
eRVR*; stop at Wk 24; f/u 24 wks No eRVR; PegIFN + RBV F/u 24 wks
24 48
12 Stop all treatment if HCV RNA > 1000 IU/mL
Wks
Stop all treatment if HCV RNA > 1000 IU/mL
Stop all treatment if HCV RNA detectable (> LLOD)
Use quantitative assay to determine if HCV RNA or > 1000 IU/mL at Wks 4 and 12
Use assay with LLOD of 10-15 IU/mL to determine if HCV RNA detectable at Wk 24
*Undetectable HCV RNA at Wks 4 and 12 of triple therapy. Telaprevir [package insert]. May 2011.

HCV RNA Thresholds for EOT Response With BOC or TVR

EOT response defined as[1,2]
HCV RNA < LLOD at EOT
Using an assay with a sensitivity of 10-15 IU/mL[1,2]
Detectable but < LLOQ values while on treatment predict lower SVR rates[3]
1. Boceprevir [package insert]. May 2011. 2. Telaprevir [package insert]. May 2011. 3. Naeger LK, et al. Intl Workshop on Clinical Pharmacology of Hepatitis Therapy 2011. Abstract R-8.

Use of HCV RNA Assays to Assess SVR With BOC or TVR-Based Therapy
SVR to pegIFN/RBV previously defined as
Absence of detectable HCV RNA in serum using assay with sensitivity of at least 50 IU/mL 6 mos after EOT[1]
SVR defined by FDA in BOC and TVR package inserts as

HCV RNA < 25 IU/mL (LLOQ) 6 mos after EOT[2-3]
1. Lindsay KL, et al. Hepatology. 2002;36:S114-S120. 2. Boceprevir [package insert]. May 2011. 3. Telaprevir [package insert]. May 2011.

Summary: Use of HCV RNA Assays in Managing Patients Receiving BOC or TVR
A quantitative assay with an LLOQ of 25 IU/mL and an LLOD of approximately 10-15 IU/mL must be used HCV RNA < LLOQ not identical to HCV RNA < LLOD
HCV RNA < LLOD required to qualify for RGT
HCV RNA < LLOQ appropriate for assessing SVR

Qualification/Endpoint RGT Futility BOC HCV RNA < LLOD at Wks 8 and 24 HCV RNA 100 IU/mL at Wk 12 HCV RNA > LLOD at Wk 24 TVR HCV RNA < LLOD at Wks 4 and 12 HCV RNA > 1000 IU/mL at Wk 4 or 12 HCV RNA > LLOD at Wk 24
EOT response SVR
HCV RNA < LLOD at EOT HCV RNA < LLOQ 24 wks after EOT
Other Assays

IL28B Genotype the Strongest Baseline Predictor of SVR With PegIFN/RBV

Odds Ratio (95% CI)
Fasting Serum Glucose < 5.6 mmol/L Hispanic vs Black Metavir F0-2 White vs Black HCV RNA 600,000 IU/mL CC vs Non-CC 0 1 2 3 4 5 6
P < .0001
P = .004
P < .0001
P < .0001
P < .0001
P < .0001
Thompson AJ, et al. Gastroenterol. 2010;139:120-129.

IL28B Genotype Also Predicts Likelihood of Achieving SVR With BOC or TVR
SPRINT-2: BOC + PR48[1] 100 80 SVR (%) 60 40 20 0 80 71 SVR (%) 59 100 80 ADVANCE*: T12PR[2] 90 71 73
60
40
n/ 44/ N = 55
CC
82/ 115 CT
26/ 44 TT
20 n/ 45/ N = 50 0 CC
48/ 68 CT
16/ 22 TT
*IL28B testing in ADVANCE was in white pts only. 1. Poordad F, et al. EASL 2011. Abstract 12. 2. Jacobson IM, et al. EASL 2011. Abstract 1369.

IL28B Genotype Predicts Likelihood of Shortened Therapy With BOC or TVR

SPRINT-2: BOC + PR[1] Eligibility for Shortened Therapy (%) Eligibility for Shortened Therapy (%) 100 80 60 40 20 0 52 89 100 80 78 57 45 40 ADVANCE*: T12PR[2]
60
n/ 118/ N = 132
CC
158/ 304 CT/TT
20 n/ 39/ N = 50 0 CC
39/ 68 CT
10/ 22 TT
*IL28B testing in ADVANCE was in white pts only. 1. Poordad F, et al. EASL 2011. Abstract 12. 2. Jacobson IM, et al. EASL 2011. Abstract 1369.

When to Consider IL28B Genotype Testing

IL28B genotype testing may be considered prior to therapy if more information about probability of response or treatment duration desired[1]
Commercially available tests
If patients have favorable CC genotype

Likelihood of SVR is high with pegIFN/RBV alone, but triple therapy may allow shorter therapy and, in one TVR study, higher SVR rates[2]
If patients have unfavorable CT/TT genotype

Likelihood of SVR is higher with triple therapy than with pegIFN/RBV[2,3]
Limited value of IL28B genotyping in treatment-experienced patients

Most have unfavorable TT or CT genotype
1. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 2. Jacobson IM, et al. EASL 2011. Abstract 1369. 3. Poordad F, et al. EASL 2011. Abstract 12.

HCV Genotype and Subtype

HCV classified into 6 major genotypes (1-6)[1]
Genotype 1 (subtypes a and b) most common in United States (~ 75%)[2]
Subtype 1a more common than subtype 1b
Determining major genotype recommended for proper clinical management and predicting likelihood of response[3]
No current recommendations regarding HCV subtype testing

1. Simmonds P, et al. Hepatology. 2005;42:962-973. 2. Zein N. Clin Microbiol Rev. 2000;13:223-235. 3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.

Higher SVR Rates With TVR in Patients With HCV Genotype 1b vs 1a

100 84 80 SVR (%) 60 40 27 20 0 79 71 47 68 88
Genotype 1a Genotype 1b
37
Tx Naive[1] T12/PR48
Relapsers*[2]
Partial Null Responders*[2] Responders*[2]
*Pooled TVR arms. 1. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 2. Zeuzem S, et al. EASL 2011. Abstract 5.

Higher SVR Rates With BOC in Patients With HCV Genotype 1b vs 1a

100 80 66 SVR (%) 60 40 20 0 59 63 50 70 65 61 73
Genotype 1a Genotype 1b
BOC RGT
BOC/PR48
Treatment Naive[1]
BOC/PR48 Treatment Experienced[2]
BOC RGT
1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.

Commercially Available HCV Genotype Assays

Genotype assay Trugene 5'NC HCV Genotyping kit INNO-LiPa HCV II Manufacturer Siemens Innogenetics Method Direct sequence analysis of the 5' noncoding region Reverse hybridization analysis using genotype-specific oligonucleotide probes located in the 5' noncoding region Reverse hybridization analysis using genotype-specific oligonucleotide probes located in the 5' noncoding region Genotype-specific real-time PCR of the 5' noncoding region and NS5b
Versant HCV Genotyping Assay 2.0 Abbott RealTime HCV Genotype II
Siemens
Abbott
Incorrect typing among major genotypes rare (< 3%)

Ghany MG, et al. Hepatology. 2009;49:1335-1374.

HCV Resistance With TVR/BOC

Resistance-associated variants occur naturally[1]
Present in 5% to 7% of subject samples prior to treatment[2,3] No apparent impact on likelihood of SVR Selected for/enriched in patients failing PI-based therapy
Following treatment failure, resistance-associated variants decline over time after withdrawal of PI but may remain detectable for up to 2.5 yrs[4,5]
Lower genetic barrier to resistance (number of mutations required to overcome virologic activity of the regimen) with genotype 1a vs 1b with BOC/TVRbased regimens Strict adherence to futility rules, ensuring patient adherence and tolerability of regimen essential to avoid resistance
1. Pawlotsky JM. Clin Liver Dis. 2003;7:45-66. 2. Telaprevir [package insert]. May 2011. 3. Boceprevir [package insert]. May 2011. 4. Vierling JM, et al. EASL 2010. Abstract 2016. 5. Sullivan JC, et al. EASL 2011. Abstract 8.

HCV Resistance Testing

Commercial resistance test for HCV NS3/4 mutations now available
Provides genetic sequence for the nonstructural proteins NS3 and NS4A of HCV genotypes 1a and 1b
Role of resistance testing prior to treatment remains to be defined

No current recommendation to perform resistance testing for patients failing therapy

Summary: Use of Genotype and Resistance Assays With BOC/TVR

IL28B genotype testing
May be considered prior to therapy if more information about probability of response or treatment duration desired[1]
HCV subtype testing No current recommendation to test prior to treatment Patients with genotype 1b may be counseled that their chance of SVR is slightly higher than 1a patients HCV resistance testing
No current recommendation regarding testing at baseline or upon treatment failure
1. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
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Understanding Optimal Use and Interpretation of Assays in HCV

This program is supported by educational grants from

Understanding the Optimal Use and Interpretation of Assays in HCV

About These Slides

Understanding the Optimal Use and Interpretation of Assays in HCV

Faculty Affiliation and Disclosure

Paul Y. Kwo, MD, has disclosed that he has received consulting

New Standard of Care for Patients With HCV

Understanding the Optimal Use and Interpretation of Assays in HCV

Patterns of Virologic Response

Wks After Start of Therapy

Understanding the Optimal Use and Interpretation of Assays in HCV

Addition of TVR or BOC to PegIFN/RBV Improves SVR in Genotype 1 Patients

PegIFN + RBV BOC/TVR + pegIFN + RBV 40-59 29-38

Understanding the Optimal Use and Interpretation of Assays in HCV

Assessment of EOT response Assessment of SVR

Additional genetic testing may help predict response to treatment

HCV RNA Assays in the Protease Inhibitor Era

Understanding the Optimal Use and Interpretation of Assays in HCV

Different HCV RNA thresholds used for RGT determination vs SVR

Understanding the Optimal Use and Interpretation of Assays in HCV

HCV RNA Assays: LLOD Is Distinct From LLOQ

Understanding the Optimal Use and Interpretation of Assays in HCV

HCV RNA Levels and Relationship to LLOD and LLOQ

Detectable/not quantifiable Not quantifiable/ not detectable

Understanding the Optimal Use and Interpretation of Assays in HCV

FDA-Approved Qualitative HCV RNA Assays

All assays report HCV RNA as detected/not detected

Understanding the Optimal Use and Interpretation of Assays in HCV

Quantitative HCV RNA Assays

Understanding the Optimal Use and Interpretation of Assays in HCV

Undetectable (Below LLOD) Detectable/Below LLOQ Above LLOQ (> 25 IU/mL)

Using HCV RNA Assays in Clinical Practice

Understanding the Optimal Use and Interpretation of Assays in HCV

Predictive Value of Baseline HCV RNA for Achieving SVR

< 800,000 IU/mL 800,000 IU/mL

800,000 IU/mL > 800,000 IU/mL

25 n/N = 0 64/ 82 207/ 281

25 n/N = 0 45/ 197/ 53 313 41/ 192/ 54 314

T12PR arm ADVANCE (TVR)[1]

BOC/PR48 BOC/PR RGT SPRINT-2 (BOC)[2]

Understanding the Optimal Use and Interpretation of Assays in HCV

Telaprevir: noncirrhotic treatment-naive patients and previous relapsers*[2,3]

Understanding the Optimal Use and Interpretation of Assays in HCV

Response-Guided Therapy Paradigm With BOC + PegIFN/RBV in Tx-Naive Patients

BOC + PegIFN + RBV 12 24

Early response stop at Wk 28; f/u 24 wks 28 36 48

BOC + PegIFN + RBV 12 24

Understanding the Optimal Use and Interpretation of Assays in HCV

Response-Guided Therapy Paradigm With BOC + PegIFN/RBV in Tx-Exp Patients

BOC + PegIFN + RBV 12 24

BOC + PegIFN + RBV 12 24

Understanding the Optimal Use and Interpretation of Assays in HCV

Response-Guided Therapy Paradigm With TVR + PegIFN/RBV in Tx-Naive Patients

TVR + PegIFN + RBV 0 4 12

eRVR stop at Wk 24, f/u 24 wks 24 48

TVR + PegIFN + RBV 0 4 12 24

Understanding the Optimal Use and Interpretation of Assays in HCV

Response-Guided Therapy Paradigm With TVR + PegIFN/RBV in Tx-Exp Patients

TVR + PegIFN + RBV 0 4 12

eRVR stop at Wk 24, f/u 24 wks 24 48

TVR + PegIFN + RBV

Understanding the Optimal Use and Interpretation of Assays in HCV

Partial Null Responders[2] Responders[2]