Future HCV Treatment Paradigms Mark Sulkowski, MD Professor of Medicine Medical Director, Viral Hepatitis Center Divisions of Infectious Diseases and Gastroenterology

Future HCV Treatment Paradigms

Mark Sulkowski, MDProfessor of Medicine

Medical Director, Viral Hepatitis CenterDivisions of Infectious Diseases and Gastroenterology/ Hepatology

Johns Hopkins Medical InstitutionsBaltimore Maryland USA

Investigational Agents for HCV

Interferons Antiviral agents

Therapeuticvaccines

Hosttarget

Replication, polyprotein processing and/or assembly

Entry

NS5Bpolymerase Inhibitors

NS3protease inhibitors

NS5Areplication complex inhibitors

2

miRNA-122 Cyclophilin

CYP inhibitors

Preclinical

Phase I

Phase II

Phase III

Filed

Boceprevir(MSD)

Telaprevir(Vertex/JJ)

TMC-435(Tibotec/JJ)

MK7009(MSD)

ITMN191/R7227 (Roche/Intermune)

BI201335(BI)

BMS650032(BMS)

GS9256(Gilead)MK5172

(MSD)

ABT450(ABT)

ACH2684(Achillion)

BMS 790052(BMS)

AZD-7295(AZN)

BMS 824393(BMS)PPI-1301

EDP-239(Enanta)

GSK

Vertex

Idenix719MSD

IFN λDebio 025/ NIM811

(Novartis)

Nitazoxamide(Romark)

Silibinine

Vitamine D

BMS

BI

ROCHE

Gilead

R7128(Roche)

GS- 7977Gilead)

BIJapan Tobacco

R0622 (Roche)Medivir (Tibotec)

GLS9393 (GSK)

BiocrystINX 189

(Inhibitrex)

BMS791325 (BMS)Filibuvir

(PFE)GS9190 (Gilead)

ANA598 (Anadys)BI201127

(BI)

Vx222 (Vertex)

ABT333ABT072 (ABT)

IDX 375 (Idenix)

IDX 184 (Idenix)

SCY-835

PPI-461

VBY-376

VX-985(Vertex)

VX-813(Vertex)

GS9451(Gilead)

RG7348(Roche)

TMC 647055 (Tibotec)

A837093(Abbott)

VX-916VX-759

CelgosivirBavituximab

Direct Acting Antivirals in Development

AVL-181(Avila)

AVL-192(Avila)

ACH-2928(Achillion)

GS-5885

Vertex

Abbott

Nucleoside NS5B

Polymerase Inhibitors

Nucleotide NS5B Polymerase Inhibitors

Non Nuc NS5BPolymerase inhibitors

NS3/4A Protease inhibitors

NS5A inhibitors

DAA combinations

Others

Cyclophilin. I

IDX 077 (Idenix)

IDX 079 (Idenix)

ABT267(ABT)

Adapted from Bourliere M, et al. Clin Res HepatolGastroenterol. 2011;35(suppl 2):S84-S95.

Edward King

Change to BMS?

Edward King

delete ". I" ?

Edward King

Change to daclatasvir?

jschulz

Is this asunaprevir?

Regimens with one DAA + pegIFN alfa/RBV

Regimens with two DAAs (± pegIFN alfa and/or RBV) IFN-free Regimens

BI 201335 (PI) Daclatasvir (NS5A) Asunaprevir (PI) GS-7977 (NI) Simeprevir (TMC-435) (PI) Alisporivir (CYP) Vaniprevir (MK-7009, PI)

Daclatasvir + asunaprevir Sofosbuvir (GS-7977) + RBV Daclatasvir + asunaprevir Alisporivir ± RBV

Investigational HCV Regimens in Phase 3

New Interferons

Peginterferon-lambda-1a

NNI = non-nucleoside NS5B inhibitor, NI = nucleoside NS5B inhibitor, PI = protease inhibitor, RBV = ribavirin, NS5A = replication complex inhibitor Cyp= cyclophilin inhibitor

Multiple Combinations Will Emerge

• Different drugs can contribute variably to each goal. Not all components must be direct-acting antivirals (DAAs).

B

C

Prevention of emergent resistance (pre-existing or de novo)

+

+

AProfound suppression of broad range of viral variants, including pre-existing variants

5

INTERFERONS +/- DAA

EMERGE: PegIFN lambda-1a vs PegIFN alfa-2a in GT 2/3 HCV Treatment-Naive Pts

• Interim analysis of randomized, blinded, active-controlled phase IIb trial

Zeuzem S, et al. EASL 2012. Abstract 10.

Treatment-naive patients infected with

genotype 2/3 HCV

(N = 118)

PegIFN lambda-1a 120 µg/wk + RBV†

(n = 29)


(n = 29)


(n = 30)

Wk 24Genotyping at baseline

†RBV dosed at 800 mg/day for genotype 2/3 patients.

PegIFN alfa-2a 180 µg/wk + RBV†

(n = 30)

• PegIFN lambda-1a 180 μg dosage chosen for phase III trials

EMERGE: Efficacy and Safety Outcomes


SVR2

4 (%

)

0

40

60

80

100

65.5

20

75.9

60.053.3

N = 29 29 30 30Lambda120 µg

Lambda180 µg

Lambda240 µg

Alfa180 µg

Adverse Event, %Lambda180 µg(n = 29)

Alfa180 µg(n = 30)

Hemoglobin low<10g/dL or ∆ > 3.4 g/dL 6.9 44.8

RBV dose reduction(Hemoglobin associated) 0 23.3

Neutrophils low< 750/mm3 0 27.6

Platelets low< 100,000/mm3 0 24.1

PegIFN dose reduction(hematologic abnormality) 0 23.3

ATOMIC: Sofosbuvir (GS-7977 (NI) + PegIFN/RBV

Kowdley KV, et al. EASL 2012. Abstract 1

GS-7977 + PR

n=125

n=155

GS-7977 + PR

GS-7977 + PR

n=52

weeks0 24

GS-7977 ± RBV

RVR

98

97

94

SVR4

92

92

94

SVR12

NA

NA

90

EOT

99

99

98

Treatment naïve, mainly Gen1 (few G4/6), non-cirrhotic

No S282T mutation seen in 4 relapse pts

12

Viral Response Rates (%)

ASPIRE: Simeprevir (PI) + PegIFN/RBV in Treatment Experienced Patients

Zeuzem S, et al. EASL 2012. Abstract 2

Simeprevir

+ P/R

weeks0 48

Treatment experienced, G1, includes cirrhotics

PegIFN + RBV

12

n=66

Simeprevir +

PegIFN/RBVPegIFN + RBV

Simeprevir + PegIFN + RBV

24

n=68

n=66

PegIFN + RBV

n=65

100

80

60

40

20

0

85*

SVR2

4 (%

)

75*

19

51*

9

37

Relapsers PartialResponders

Null Responders

* Represents pooled simeprevir duration at 150mg dose

Quad Therapy: SVR12 with 16 Weeks of Tegobuvir and GS-9256 plus Peginterferon-alfa 2a and Ribavirin in

Treatment-Naïve Genotype 1 HCV Patients

Patients with vRVR → 16 or 24 wks

Group 1N = 163

Very rapid virologic response (vRVR) = HCV RNA <LLOQ at Week 2RVR = HCV RNA <LLOQ at Week 4

PEG + RBV

GS-9256 150 mg BID +TGV 20 mg BID + PEG + RBV

Day 1 Wk 48Wk 16 Wk 24 Response-Guided Therapy

SVR12

98% 95%

0%

20%

40%

60%

80%

100%

SVR 4 SVR 12

Nelson DR. EASL 2010. Abstract 12

Per protocol/ completer analysis

CYCLOPHILIN INHIBITOR + RBV

VITAL-1: Alisporivir-Based Therapy for Trt-Naive GT2/3 Pts

Pawlotsky JM, et al. EASL 2012. Abstract 1405.

Treatment-naive patients

with chronic GT 2/3 HCV infection

(N = 340)

Alisporivir 1000 mg QD

(n = 83)

Alisporivir 600 mg QD + RBV

(n = 84)


(n = 94)

Wk 24Stratified by HCV RNA and HCV genotype

Alisporivir 600 mg QD + PegIFN

(n = 39)

PegIFN alfa-2a/RBV (n = 40)

All pts received alisporivir loading dose of 600 mg BID during first wk. PegIFN alfa-2a dosed 180 µg/wk. RBV dosed 800 mg/day.

Wk 4: RVR assessed Wk 6

24-wkF/U

Alisporivir 600 mg QD + PegIFN/RBV

Alisporivir 1000 mg QD




Alisporivir 800 mg QD + RBV 800 mg/day


Alisporivir 600 mg QD + PegIFN

RVR:

No RVR:

RVR:

No RVR:

RVR:

No RVR:

RVR:

No RVR:

VITAL-1: SVR12 by Per-Protocol Analysis

• High SVR rates with alisporivir-based therapy, including IFN-free regimens– However, development of alisporivir currently on hold due to 3 cases of pancreatitis

(with 1 death) in > 1800 patients treated to date

Pawlotsky JM, et al. EASL 2012. Abstract 1405..

Overall SVR12 SVR12 in Pts Receiving IFN-free Therapy

SVR1

2 (%

)

0

40

60

80

100

20

ALV1000

81 83 81 77

58

ALV600RBV

ALV800RBV

ALV600Peg

P/R0

40

60

80

100

20

ALV1000

8293 91

ALV600RBV

ALV800RBV

82 84 93 39 40n = 17 29 32n =

PI +/- NON-NUCLEOSIDE POLYMERASE INHIBITOR +/- NS5A INHIBITOR +/- RBV

Co-Pilot (M12-746) Study: ABT-450/r + ABT-333 Treatment

ABT-450/r 250/100 mg QD + ABT-333 400 mg BID + RBV

Arm 1Treatment-naïve (N=19)


Arm 2Treatment-naïve (N=14)


Arm 3Prior P/R non-responders (N=17)

12 Weeks (On Treatment) Follow UpPeriod

Poordad F, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1399.

Co-Pilot Study: Demographics and Baseline Characteristics

Arm 1N=19

Arm 2N=14

Arm 3N=17

Male, n (%) 10 (52.6) 14 (100) 11 (64.7)White, n (%) 15 (78.9) 12 (85.7) 13 (76.5)Hispanic/Latino, n (%) 3 (15.8) 0 4 (23.5)Mean Age ± SD (years) 53.6 ± 9.78 50.9 ± 10.45 52.3 ± 9.03Mean BMI ± SD (kg/m2) 27.3 ± 3.84 24.6 ± 3.08 27.6 ± 4.65

IL28 genotype , n (%) CC CT TT

10 (52.6)7 (36.8)2 (10.5)

5 (35.7)7 (50.0)2 (14.3)

012 (70.6)5 (26.3)

HCV genotype, n (%) 1a 1b

17 (89.5)2 (10.5)

11 (78.6)3 (21.4)

16 (94.1)1 (5.9)

HCV RNA Mean ± SD (log10 IU/mL) >800,000 IU/mL, n (%)

6.25 ± 0.8014 (73.7)

6.44 ± 1.1511 (78.6)

6.93 ± 0.4717 (100)

Non-responder status Partial responder Null responder

- - 11 (64.7)6 (35.3)


Co-Pilot Study: Virologic Results


ABT-267 + PegIFN/RBV in treatment-naïve subjects Results

cEVR, complete early virological response; LLOD, lower limit of detection (15 IU/mL); LLOQ, lower limit of quantitation (25 IU/mL); P/R, PegIFN/RBV;SE, standard error; QD, once daily

• Safety:− ABT-267 had an adverse event profile similar to placebo− No serious adverse events

EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1210

Placebo ABT-267 5 mg QD

ABT-267 50 mg QD

ABT-267 200 mg QD

0

10

20

30

40

50

60

70

80

90

100

33

87.5 8675

33

12.5

<LLOQ, <LLOD

Pati

en

ts a

ch

ievin

g W

eek 1

2 c

EV

R

(%)

66%

100%

86%

75%

Week 12 cEVR rates

A Randomized, Open Label, Multi-center Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450

With Ritonavir (ABT-450/r) in Combination With ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) in

Treatment-Naïve and Null Responder Subjects With Genotype 1 Chronic Hepatitis C Virus Infection

• N = 560 • 14 active treatment arms testing combinations of DAAs and

RBV– No interferon

• This study is ongoing, but not recruiting participants

ClinicalTrials.gov Identifier: NCT01464827

http://clinicaltrials.gov/ct2/show/NCT01464827

SOUND-C2: BI 201335 + BI 207127 ± RBV in

Trt-Naive GT1 Pts


Treatment-naive pts with GT1 HCV

[7% to 17% in each group had

cirrhosis]

(N = 362)

BI 201335 120 mg QD + BI 207127 600 mg TID + RBV

(n = 81)


(n = 80)


(n = 77)

Wk 16

BI 201335 120 mg QD + BI 207127 600 mg BID + RBV

(n = 78)

BI 201335 120 mg QD + BI 207127 600 mg TID, no RBV

(n = 46)*

Stratified by HCV subtype and IL28B genotype

*Randomization to this arm stopped early due to US FDA concerns regarding lack of RBV.

12-wk follow-up

for SVR12

Wk 28 Wk 40

Weight-based RBV dosing (1000-1200 mg/day).

SOUND-C2: Higher SVR12 in Pts With GT 1b HCV, IL28B CC, BID Dosing


SVR1

2 (%

)

SVR1

2 (%

)

0

40

60

80

100

20n/N =

32

7584 82

1anon-CC

1aCC

1bnon-CC

1bCC

BID28wkRBV

TID28wk

TID40wkRBV

TID28wkRBV

TID16wkRBV

32

71

38

71

42

62

32

82

53

0

1a non-CC All 1b and 1a-CC

SVR according to IL28B and HCV subtype:BID28wk + RBV (ITT)

SVR according to IL28B and HCV subtype(ITT)

0

40

60

80

100

20

7/22 6/8 31/37 9/11

HCV Subtype and IL28B Genotype

4-Drug Therapy With GS-5885, GS-9451, Tegobuvir, and RBV in Tx-Naive GT1 HCV

• Interim analysis of randomized phase II study

Sulkowski M, et al. EASL 2012. Abstract 1421.

Tx-naive patients with chronic GT1

HCV infection(N = 140)

GS-5885 30 mg QD +GS-9451 200 mg QD + Tegobuvir 30 mg BID +

Ribavirin (n = 46)

Randomized 1:2; stratified by HCV RNA

(≤ vs > 800,000 IU/mL) and HCV 1 subtype (1a vs 1b)

*Patients with HCV RNA ≥ 25 IU/mL at Wk 2 offered rescue therapy including pegIFN or study discontinuation.†Patients rerandomized if HCV RNA < 25 IU/mL at Wks 2-10.


Ribavirin (n = 94)

Wk 2* Wk 12 Wk 24


Ribavirin

Follow-up

Rerandomized†

Follow-upfor SVR24

SVR-4 rates among patients with HCV RNA < 25 IU/mL at week 2

Effect of IL28B genotype, subtype and NS5A dose on week 2 response and breakthrough

Viral breakthrough was associated with resistance to PI, NS5A and NNI

Daclatasvir (NS5A) + Asunaprevir (PI)

Suzuki F, et al. EASL 2012. Abstract 14

100

80

60

40

20

0

91

SVR2

4 (%

)

9/10

n=21Weeks

0 24

Gen1b, non-cirrhotic

Daclatasvir + Asunaprevir

Daclatasvir + Asunaprevir

n=22

64Nullresponder

IFNintolerant

Nullresponder

IFN ineligible and intolerant

Among pts with breakthrough (7%) or relapse (9%), low plasma concentrations of DAC and ASU

NUCLEOS(T)IDE ANALOGUE POLYMERASE INHIBITOR +/- PI +/- NS5A INHIBITOR +/- RBV

INFORM-SVR: Mericitabine + danoprevir/ritonavir ± RBVin treatment-naïve GT-1: Study design

• Randomised Phase 2b study of response-guided mericitabine + ritonavir-boosted danoprevir ± RBV in treatment-naive GT-1 HCV patients– n=169: 67% HCV GT-1a; 69% IL28B non-CC

Week 24Week 12

Mericitabine 1000 mg BD + danoprevir/ritonavir

100/100 mg BD + RBV 1000/1200 mg QD

Mericitabine + danoprevir/ritonavir + RBV

Mericitabine + danoprevir/ritonavir + RBV

A

B

apatients with eRVR were re-randomised at Week 12 to maintain or stop treatmentbDue to unacceptable relapse rates, re-randomisation was halted and patients in Arm B on active treatment were offered PegIFN/RBV BID, twice daily; eRVR, early rapid virological response; GT, genotype; PegIFN, pegylated interferon; RBV, ribavirin

No treatment

No eRVR

Mericitabine 1000 mg BD + danoprevir/ritonavir

100/100 mg BD + placebo

Mericitabine + danoprevir/ritonavir + placebob

Mericitabine + danoprevir/ritonavir + placebob

No treatmenta

No eRVR

Week 4

EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1412

eRVRa

eRVRa

INFORM-SVR: Mericitabine + danoprevir/ritonavir ± RBVin treatment-naïve GT-1 (Abstract 1412): Results

Mericitabine + danoprevir/ritonavir

+ RBV

Mericitabine + danoprevir/ritonavir

+ placebo

HCV RNA ≤15 IU/mL at Week 4 (%) 91 93

Mericitabine 1000 mg + danoprevir/ritonavir + RBV scheduled for 24 weeks

(n=63)

SVR8: Overall, % (n) 41 (26/63)

GT-1a 26 (11/42)

GT-1b 71 (15/21)

AEs, adverse events; SVR8: sustained virological response at Week 8 EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1412

• Four serious AEs and two discontinuations due to AEs in overall population

G S - 7 9 7 7 + R B V

GS-7977 + RBV

G S - 7 9 7 7 + P E G + R B V

GS-7977 + PEG + RBVG S - 7 9 7 7 + R B V

GS-7977 + RBVG S - 7 9 7 7 + P E G + R B V

GS-7977 + PEG + RBVG S - 7 9 7 7 + P E G + R B V

GS-7977 + PEG + RBV

n= 9

n= 10

n= 10

G S - 7 9 7 7

GS-7977

G T 2 / 3 T r e a t m e n t- N a ïv e ( G S - 7 9 7 7 + R B V + P E G )

GT 2/3 Treatment-Naïve (GS-7977 + RBV +PEG) G S - 7 9 7 7 + R B V ( G T 1 N u l l R e s p o n d e r s )

GS-7977 + RBV (GT 1 Null Responders) G S - 7 9 7 7 + R B V ( G T 1 T r e a t m e n t- N a iv e )

GS-7977 + RBV (GT 1 Treatment-Naive) G S - 7 9 7 7 + R B V ( G T 2 / 3 T r e a t m e n t- E x p e r ie n c e d )

GS-7977 + RBV (GT 2/3 Treatment-Experienced)

n= 11

n= 10

n= 10

n= 10

n= 25

n= 25

Wk 4 Wk 8 Wk1 2Wk 0

GT 2/3 Tx-naive

Gane E, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1113.

Electron Study: Treatment of GS-7977

Electron Study:Virologic Response

GT 2/3Treatment-naïve

8 wks(N=10)

GT 1 Null Responders

12 wks(N=10)

GT 1Treatment-naïve

12 wks(N=25)

GT 2/3 Treatment- experienced

12 wks(N=25)

Week 1 6/10 (60) 1/10 (10) 7/25 (29) 8/25 (32)

Week 2 10/10 (100) 7/10 (70) 17/24 (71) 21/25 (84)

Week 4 10/10 (100) 10/10 (100) 25/25 (100) 25/25 (100)

EOT 10/10 (100) 9/9 (100) 25/25 (100) 21/21 (100)

SVR 4 10/10 (100) 1/9 (11) 22/25 (88) 12/15 (80)

SVR 8 10/10 (100) 1/9 (11) -

SVR 12 10/10 (100) - - -

Patients with HCV RNA <LOD Over Time, n/N (%)

Gane E, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1113.

Study AI444-040: Treatment with GS-7977 + BMS-790052

RBV: 1000-1200 mg daily according to body weight for GT1 patients ; 800 mg daily for GT2/3 patients

N = 15

N = 16

N = 14Chronic HCV GT1a/1b or GT2/3

infection, treatment-naive

SVR12Week 24 SVR4 SVR48Week 1 Week 4 Week 12

Group C: (GT1a/1b) DCV 60 mg QD + GS-7977 400 mg QD

Group D: (GT2/3) DCV 60 mg QD + GS-7977 400 mg QD Follow-up

Group E: (GT1a/1b) DCV 60 mg QD + GS-7977 400 mg QD + RBV Follow-up

N = 14

Group F: (GT2/3) DCV 60 mg QD +GS-7977 400 mg QD + RBV Follow-up

N = 15

N = 14

Group A: (GT1a/1b) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Follow-up

Group B: (GT2/3) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Follow-up

Follow-up

Sulkowski M, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1422.

Study AI444-040: Key Results

mITT analysis, bars not reaching 100% after Week 4 reflect missing values.PT, post treatment


Week 2 Week 4 Week 12 Week 24(EOT) PT Week 4

N=

% < LOD

% < LLOQ67 79 67 100 100 100 100 93 100 87 86 93 100 100 100SVR4

Study AI444-040: SVR-4 according to genotype 1A/B and IL28B

• Overall SVR4 – 95.5% across GT 1,2 & 3• GT1: 100% of patients (44/44) achieved SVR4 • No difference in SVR4 by HCV GT1 subtype or IL28B genotype• Ribavirin did not increase the magnitude of HCV RNA decline or influence SVR


IL28B Genotype(rs12979860)

Study AI444-040: GT2/3 Naïve


N=44

GT2/3SVR4=40/44

GT2Total n=26

SVR4=24/26

GT3Total n=18

SVR4=16/18

GT2/3 – No RBVSVR4=28/30

2 viral failures

GT2/3 + RBVSVR4=12/14

2 LTFU

1 breakthrough (3a)1 relapse (3a)

2 LTFU (2a, last RNA UND)

2012 - 201X: Multiple DAA Combinations in Developmen

• Clinical trials to determine “best” combinations and minimum duration needed to achieve cure – Multiple regimens may lead to reduced cost per

cure• Role of Interferon alfa (lambda?) will evolve

but not become extinct

TYPICAL DAY IN THE CLINIC, JUNE 201X

Patient 1• 47 year old woman presents after being declined for

life insurance – Infection likely due to blood shortly after birth – PMH: None– Social history: Married with 3 children; Recent change to

new job with more responsibility– HCV genotype 1B; IL28B CC; Biopsy shows no fibrosis

• Treatment: – Oral therapy --- combination of 2 DAAs with no IFN and no

RBV for 12 weeks ($$)– PegIFN/RBV ($)

Patient 2• 66 year old man infected at age 20 via IDU

– PMH: type 2 DM, hypertension, obesity, mild renal insufficiency; anemia; heroin use off/on (methadone); depression (incompletely controlled)

– HCV genotype 1A; IL28B TT; Biopsy shows cirrhosis • Treatment:

– Multiple DAAs with nucleos(t)ide analogue ($$$) – No IFN due to contraindications

Patient 3• 59 year old man otherwise healthy

– HCV genotype 1A; IL28B TT; Biopsy shows Ishak 3/6 fibrosis

• Prior therapy – 1997: IFN alfa/RBV – stop at wk 24 with HCV RNA 5,500

copies/mL– 2011: PegIFN/RBV/Telaprevir – stop at wk 5

• Week 0: 11,389,000 IU/mL (7.06 log10)• Week 2: 17,710 IU/mL (4.25 log10)• Week 4: 153, 060 IU/mL (5.18 log10)

• Treat: Multiple DAAs +/- IFN +/- RBV ($$$$)

Patient 4• 59 year old man with decompensated liver

disease – MELD = 25 – Ascites – HCC less than 2 CM on MRI

• Treatment:– :Multiple DAAs – pre or post-transplant ($$$$)– 5 year survival for HCV expected to be similar to

similar to HBV

Patient 5• 22 year old man tested positive for HCV EIA using

finger stick test while attending needle exchange – Actively injecting heroin (~30 USD/day) uses new

needles when he can– Staying with “friends”– HIV seronegative

• Lost to follow-up • Treatment:

– Contingent Incentive Care x oral DAAs for 12 weeks ($$)– Cost-effective with individual and public health benefit?

Future Treatment Paradigms

• Personalized medicine– Cost– Virus – 1A or 1B or other genotype; Resistance to

DAAs– Patient – cirrhosis, ESLD, HCC, willing and able to

take IFN alfa; substance abuse? • Effectiveness may be limited by failure to

translate to the infected populations

Documents

Future HCV Treatment Paradigms Mark Sulkowski, MD Professor of Medicine Medical Director, Viral Hepatitis Center Divisions of Infectious Diseases and Gastroenterology