Escenarios futuros sin IFN

¿y sin RBV?

III Curso Hepatitis

Sociedad Chilena de Infectología Agosto 2014

Dr. Carlos Beltrán

Hospital Barros Luco Trudeau

Universidad de Santiago

Grupo SidaChile

¿Cuál es la magnitud del problema

en Chile?

ENS 2003: 0,12% RIBA

Donantes 0,3%

Ref.: 1,15% (RIBA 0,83%)

Soza A, et al. Rev Med Chile 2006; 134: 777 - 788

¿Cuál es la prevalencia en Chile?

Prevalencia VHB – VHC en VIH

91,3%

8,7%

Negativo Positivo

97,7%

2,3%

Negativo Positivo

HBsAg VHC

N = 4.904 N = 3.191

72 casos 426 casos

Evolución serología basal VHC

1,9%1,6%1,7%2,0%1,7%3,6%4,8%2,3%0,0%7,7%

0%

20%

40%

60%

80%

100%

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

VHC (-) VHC (+)VHB: 8,7%

VHC: 2,3%

VHC crónico en USA:

Subdiagnosticado y no tratado

Hepatitis C Monitor. Ipsos Healthcare.

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Nu

mb

er

(in

‘000s)

Prevalence Diagnosed Treated

4.1 M

1.6 M

89,000

38% Diagnosed

5.5% Treated

Unaware of Infection

2.7-3.9 million

infected

50% HCV

detected

32% to 38%

referred for care

7% to 11%

treated

Asrani S, et al. Curr Gastroenterol Rep. 2014;16:381

*Mortality rates = HBV, HCV, HIV listed as cause of death

Because decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for

each type of infection

Tasas de mortalidad en USA,

1999-2007

Ly KN, et al. Ann Intern Med. 2012;156:271-278

7

6

5

4

3

2

1

0

Rate

per

100,0

00 P

Y*

Yr

Hepatitis B

Hepatitis C

HIV

Replicación VHC asociada con mayor

mortalidad general

Lee MH, et al. J Infect Dis. 2012;206:469-477

All Causes

Cu

mu

lati

ve M

ort

ality

(%

)

30.1%

12.8%

12.4%

P < .001 for comparison among 3 groups

P < .001 for HCV RNA detectable vs

undetectable

Anti-HCV seropositives, HCV RNA detectable

Anti-HCV seropositives, HCV RNA undetectable

Anti-HCV seronegatives

Follow-up (Yrs)

0 2 4 6 8 10 12 14 16 18 20

35

30

25

20

15

10

5

0

SVR y complicaciones de VHC

7.7%

15.6%

HC

C In

cid

en

ce (

%)

0

50

40

30

20

10

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (Yrs)

No SVR

SVR

P = .0009

Purevsambuu T, et al. EASL 2014. Abstract O125.

P = .007 P = .1

P = .04 25

20

15

10

5

0

Rate

s o

f d

e N

ovo

IR

(%

)

Overall HCV GT

1/4

HCV GT

2/3

17%

7%

16%

8% 7%

20%

17/

230

21/

124

6/

78

15/

94

11/

152

6/

30

Non-SVR SVR

Aghemo A, et al. Hepatology. 2012;58:1681-1687.

Distribución mundial por genotipo

Aumento de la SVR de VHC G1 S

VR

(%

)

6%

16%

6 Months

34%

55%

>70%

Jacobson IM. Clin Gastroenterol Hepatol. 2009;7:921-930.

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

Ghany MG, et al. Hepatology. 2011;54:1433-1444.

42% 39%

IFN

12 Months 6 Months

IFN + RBV

12 Months 12 Months

PegIFN

12 Months DAA PegIFN + RBV

PegIFN + RBV

1991

1998

2001

2011

Standard Interferon

Ribavirin

Peginterferon

Direct Acting Antivirals

Aumento de eficacia en falla previa,

especialmente “relapsers” y “partial”

Antivirales de acción directa

NS3/4A NS5A NS5B

Function Serine Protease Component of HCV

Replication Complex

RNA-dependent RNA

polymerase

Drugs Covalent

Boceprevir

Telaprevir

Non-covalent

Faldaprevir

Simeprevir

ABT-450

Asunaprevir

MK-5172

Ledipasvir

Daclatasvir

Ombitasvir

MK-8742

PPI-668

Nucleoside analogs

Sofosbuvir

Non-nucleoside

BMS-791325

Dasabuvir

Deleobuvir

C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B

Core Envelope Glycoproteins Protease Serine

Protease

Helicase Serine

Protease

Cofactor

RNA-dependent

RNA polymerase Component of

HCV Replicase

Preferred Treatment

Recommendations: Initial Therapy

or Relapsed after Prior PR

AASLD-IDSA

Genotype 1 IFN eligible

IFN ineligible†

Sofosbuvir + PR 12 weeks

Sofosbuvir + simeprevir* ± RBV 12 weeks

Genotype 2 Sofosbuvir + RBV 12 weeks

Genotype 3 Sofosbuvir + RBV 24 weeks

Genotype 4 IFN eligible

IFN ineligible

Sofosbuvir + PR 12 weeks

Sofosbuvir + RBV 24 weeks

Genotype 5 or 6 Sofosbuvir + PR 12 weeks

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version March 21, 2014

PR: Pegylated interferon + Ribavirin.

† Currently recommended only for patients who require immediate treatment.

*For genotype 1a, baseline resistance testing for the Q80K polymorphism should be performed and alternative treatments considered if this mutation is present.

Do not treat decompensated cirrhosis with PegIFN or simeprevir

Preferred Treatment

Recommendations: Partial or Null

Response to Prior PR†

AASLD-IDSA

Genotype 1

Prior PR Sofosbuvir + simeprevir ± RBV 12 weeks

Prior PR-based

triple therapy

Sofosbuvir 12 weeks + PR 12-24 weeks

Genotype 2 Sofosbuvir + RBV 12 weeks

Genotype 3 Sofosbuvir + RBV 24 weeks

Genotype 4 Sofosbuvir + PR 12 weeks

Genotype 5 or 6 Sofosbuvir + PR 12 weeks

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version March 21, 2014

PR: Pegylated interferon + Ribavirin. †Consideration should be given to postponing treatment, pending release of new drugs for patients with limited hepatic fibrosis (F 0-2)

Do not treat decompensated cirrhosis with PegIFN or simeprevir

EASL HCV Guidelines 2014: Genotype 1

Genotype Options for Therapy

Genotype 1*

PegIFN/ribavirin + sofosbuvir: 12 wks (A1)

PegIFN/ribavirin + simeprevir†: 12 wks, followed by 12 wks of pegIFN/

ribavirin in previously untreated pts and prior relapsers (A1), or 36 wks of

pegIFN/ribavirin in previous partial responders and null responders (B1)

PegIFN/ribavirin + daclatasvir (genotype 1b only; B1): 12 wks followed by 12

wks of pegIFN/ribavirin alone or a further 12 wks of pegIFN/ribavirin +

daclatasvir (response-guided therapy) (B2)

Sofosbuvir + ribavirin: 24 wks for interferon-intolerant pts only, where no

other interferon-free option available (B2)

Sofosbuvir + simeprevir: 12 wks (ribavirin may be added for previous

nonresponders & cirrhotics) (B1)

Sofosbuvir + daclatasvir: 12 wks in previously untreated pts; 24 wks in

treatment-experienced patients (including TVR/BOC-experienced patients)

(ribavirin may be added in previous nonresponders and cirrhotics) (B1)

EASL. J Hepatology. 2014;60:392-420.

*In settings where recommended options are not available, treatment with pegIFN/ribavirin + TVR or BOC remains acceptable. †Not recommended in pts with genotype 1a and detectable Q80K polymorphism.

Argumentos para el tratamiento IFN-

Free de VHC

Inconvenientes de las terapias basadas en IFN

Tolerabilidad

Alto porcentaje de pacientes no elegibles para IFN

Larga duración del tratamiento

Bajas tasas de SVR comparado con los antivirales

PR: ~40-50% en pacientes naïve

Terapia triple PR + Boceprevir o Telaprevir: ~70%

Muchos factores del paciente y el virus que afectan la

elegibilidad o la tasa de respuesta (Raza, IL28B,

cirrosis, tratamiento previo, etc)

Desarrollo de resistencia

Uso inyectable

GT1 HCV Tx Naive: SVR Rates With

12 Wks of IFN-Free Tx in Phase II Studies

Few or no cirrhotic patients included in above studies

Usually monoinfected patients

1. Lalezari LP, et al. EASL 2013. Abstract 845. 2. Gane E, et al. EASL 2013. Abstract 14.

3. Lawitz E, et al. AASLD 2013. Abstract 215. 4. Sulkowski MS, et al. AASLD 2012. Abstract LB-2.

5. Kowdley K, et al. EASL 2013. Abstract 3. 6. Everson G, et al. AASLD 2013. Abstract LB-1.

7. Lawitz E, et al. AASLD 2013. Abstract 76. 8. Sulkowski M, et al. EASL 2013. Abstract 1423.

Regimen N Study SVR 4/12, %

SOF (NS5B) + RBV 25 QUANTUM[1] 56

SOF (NS5B) + RBV 25 ELECTRON[2] 84

SOF (NS5B) + LDV (NS5A) 19 LONESTAR[3] 95

SOF (NS5B) + DCV (NS5A) ± RBV 82 AI-444040[4] 98-100

ABT-450 (PI) + ABT-267 (NS5A) + ABT-333 (NS5B) ± RBV 158 AVIATOR[5] 94

DCV (NS5A) + ASV (PI) + BMS-791325 (NS5B) 161 A1443-014[6] 92

MK-5172 (PI) + MK-8742 (NS5A) ± RBV 65 C-WORTHY[7] 96-100

ION 1: SOF/LDV FDC

RBV for 12 or 24

Wks in Treatment-Naive GT1 Patients

Open-label phase III trial[1,2]

15% to 17% of participants had cirrhosis

Mangia A, et al. EASL 2014. Abstract O164

Afdhal N, et al. N Engl J Med. 2014;370:1889-1898

Sofosbuvir/ledipasvir 400/90 mg FDC tablet once daily; weight-based RBV 1000-1200 mg/day.

SOF/LDV + RBV (n = 217)

SOF/LDV (n = 214)

Wk 24

Treatment-naive pts with HCV GT1

(N = 865)

SOF/LDV + RBV (n = 217)

SOF/LDV (n = 217)

Wk 12

ION 2: over 100 previous null responders

The same 4 arms

ION 1: SVR12 With 12 or 24 Wks SOF/LDV

RBV in Tx-Naive Pts by Cirrhosis Status

SVR12 rates did not differ by

GT1a vs GT1b in any treatment

arm

Virologic failure: 1 breakthrough;

2 relapses

Higher incidence of AE and lab.

abnormalities in the RBV-

containing arms

Fatigue, insomnia, asthenia,

irritability, rash, cough,

pruritus, and anemia

AE rates were generally higher in

the 24-week arm

Mangia A, et al. EASL 2014. Abstract O164

Afdhal N, et al. N Engl J Med. 2014;370:1889-1898

No cirrhosis Cirrhosis

179/180

32/34

178/184

33/33

181/184

31/33

179/181

36/36

12 Wks 24 Wks

SOF/LDV + RBV SOF/LDV + RBV SOF/LDV SOF/LDV

SV

R1

2 (

%)

100

80

60

40

20

0

99 94 97 100 100 99 94 98

ION-2: SOF/LDV FDC

RBV for 12 or 24

Wks in Treatment-Experienced, Cirrhotic

Patients 95,4

100 98,9 98,9

86,481,8

100 100

0

20

40

60

80

100

LDV/SOF

SV

R12, %

Pati

en

ts

LDV/SOF + RBV

LDV/SOF LDV/SOF + RBV

12 Wks 24 Wks

n=87 n=22 n=89 n=22 n=87 n=22 n=89 n=22

Afdahl N, et al. NEJM 2014. DOI 10/1056

Afdhal N, et al. NEJM 2014 DOI: 10.1056

Cir

rhosis

Cir

rhosis

Cir

rhosis

ION 2: Efficacy rate 99% in 24 Wks

Between 96 AND 100% with 12 Wks

In cirrhotic – null responders 24 Wks better

ION-3: Sofosbuvir/Ledipasvir + RBV in

Treatment-Naïve, HCV Genotype 1

Kowdley KV, et al. N Engl J Med. 2014;April 10. [Epub ahead of print].

Sofosbuvir/Ledipasvir QD (n=215)

Sofosbuvir/Ledipasvir QD (n=216)

Phase 3

Open-label, non-inferiority

Genotype 1, Treatment-naïve

Non-cirrhotic

8 vs 12 weeks

Wk 0 8 12 24

ELECTRON Study arm

Sofosbuvir + Ledipasvir + RBV for 6 weeks

Treatment naïve, non – cirrhotics

SVR 68%

Sofosbuvir/Ledipasvir QD + RBV (n=216)

SV

R12 (

%)

94% 95%

No RBV (n=215)

8 wks 8 wks, with RBV 12 wks

RBV (n=216)

8 Weeks

No RBV (n=216)

93%

*Met non-inferiority criteria (12% margin) for all between group comparisons.

12 Weeks

Overall SVR12* Sofosbuvir/Ledipasvir QD

SV

R1

2 (

%)

93% 95%

Genotype 1a (n=171/172/172)

Genotype 1b (n=43/44/44)

92% 98% 98% 96%

SVR12 by HCV Subtype

Kowdley KV, et al. N Engl J Med. 2014;April 10. [Epub ahead of print].

ION-3: Sofosbuvir/Ledipasvir + RBV in

Treatment-Naïve, HCV Genotype 1

COSMOS: Simeprevir + Sofosbuvir

RBV in Genotype 1 HCV Patients

Randomized phase IIa study

Simeprevir 150 mg QD; sofosbuvir 400 mg QD; weight-based RBV 1000-1200 mg/day.

Patients With GT1 HCV

Cohort 1: Previous null responders,

F0-F2[1]

(N = 80)

Cohort 2: Naives and previous null

responders, F3-F4[2] (N = 87)

Simeprevir + Sofosbuvir + RBV (n = 30)

Simeprevir + Sofosbuvir (n = 16)

Wk 12 Wk 24

Simeprevir + Sofosbuvir (n = 14)

Simeprevir + Sofosbuvir + RBV (n = 27)

1. Sulkowski M, et al. EASL 2014. Abstract O7. 2. Lawitz E, et al. EASL 2014. Abstract O165.

0

20

40

60

80

100

SV

R12 (

%)

Simeprevir + Sofosbuvir

PR Null responders F0 – F2

93%

24 Weeks (n=15/24)

12 Weeks (n=14/27)

No RBV With RBV

96% 93%

79%

Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O7.

Jacobson IM, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.

COSMOS: Simeprevir + Sofosbuvir ±

RBV in Genotype 1 HCV Patients

SAPPHIRE I & II: ABT- 450/RTV/Ombitasvir +

Dasabuvir + RBV in Noncirrhotic GT1 Pts

Double-blind, placebo-controlled phase III trials in treatment-naive

(SAPPHIRE I) and treatment-experienced (SAPPHIRE II) GT1 HCV pts

Placebo (n = 158)*

ABT-450/RTV/Ombitasvir + Dasabuvir + RBV (n = 473)

Wk 12

1. Feld JJ, et al. EASL 2014. Abstract O60. 2. Feld JJ, et al. N Engl J Med. 2014;370:1594-1603.

3. Zeuzem S, et al. EASL 2014. Abstract O1. 4. Zeuzem S, et al. N Engl J Med. 2014;370:1604-1614.

ABT-450/RTV/ombitasvir 150/100/25 mg once daily; dasabuvir 250 mg twice daily; RBV 1000-1200 mg/day.

*Placebo recipients crossed over to active treatment regimen at Wk 12.

Treatment-naive noncirrhotic pts with HCV GT1[1,2]

(N = 631)

Treatment-experienced noncirrhotic pts with HCV GT1[3,4]

(N = 394) Placebo (n = 97)

ABT-450/RTV/Ombitasvir + Dasabuvir + RBV (n = 297)

SAPPHIRE I & II: SVR12 by HCV Subtype and

Previous Treatment

Zeuzem S, et al. EASL 2014. Abstract O1. Zeuzem S, et al. N Engl J Med. 2014;370:1604-1614.

Previous Response

Relapse Partial response Null response

SV

R12 (

%)

100

80

60

40

20

0 All Patients GT1a GT1b

95.3 100

95.2 94.0 100 100

95.4 97.2 94.9

SAPPHIRE-1:

GT1 Tx-Naive Noncirrhotic Pts:

ABT-450/r 267 FDC

+ ABT-333 + RBV for 12 Wks

n/N = 455/

473

307/

322

148/

151

100

80

60

40

20

0

SV

R12 (

%)

96 95 98

Overall GT1a GT1b

TURQUOISE-II: ABT-450/r/ABT-267 +

ABT-333 + RBV in Compensated Cirrhotics

Poordad F, et al. N Engl J Med 2014; 370: 1973-1982.

3D + RBV (n=208)

Wk 0 12 24

3D + RBV (n=172)

Phase 3

Open-label Genotype 1

Treatment-naïve and

PR experienced

Child-Pugh A

SV

R12 (

%)

92% 96%

12-Week 24-Week

SV

R1

2 (

%)

89% 98% 94% 100%

12-Week 24-Week

1a

1b

PEARL-III: ABT-450/r/Ombitasvir + Dasabuvir

+ RBV in Treatment-Naïve, HCV Genotype 1b

Ferenci P, et al. N Engl J Med 2014; 370: 1983-1992

Phase 3

Double-blind

Genotype 1b; Treatment-naïve

Non-cirrhotic

3D + RBV (n=210)

Wk 0 12 24

3D + Placebo (n=209)

0

20

40

60

80

10099% 99%

3D 3D + RBV

SV

R1

2 (

%)

Non-inferiority criteria (10.5% margin)

met for 3D + RBV versus 3D without RBV

SVR12 rates in both arms were similar

across patient subgroups

Baseline HCV RNA, IL28B, fibrosis

stage, gender, race

HALLMARK-DUAL: Daclatasvir +

Asunaprevir in Patients With GT1b HCV

Better results in Genotype 1b

AI447-028: double-blinded, placebo-controlled phase III trial

Manns M, et al. EASL 2014. Abstract O166

Daclatasvir 60 mg once daily; asunaprevir 100 mg twice daily.

*Patients allocated placebo crossed over into a separate study after 12 wks.

Placebo* (n = 102)

Daclatasvir + Asunaprevir (n = 203)

Daclatasvir + Asunaprevir (n = 235)

Daclatasvir + Asunaprevir (n = 205)

Wk 24

Treatment-naive (N = 305)

Previous null or partial responders (N = 205)

Interferon ineligible/intolerant

(N = 235)

Wk 12

GT1b HCV

HALLMARK-DUAL Study: Daclatasvir +

Asunaprevir in HCV Genotype 1b

SVR12 rates were similar

Non-cirrhotic (85%) and cirrhotic (84%)

Age, gender, race, IL28B genotype

SVR12 rates were lower with baseline

thrombocytopenia (<90 versus >90 x 109

cells/L)

Overall: 71% versus 86%

Advanced fibrosis/cirrhosis: 69% versus 78%

Non-SVR12 achievers (3 treatment arms)

Breakthroughs (4%, 13%, 9%)

Relapse (3%, 4%, 6%)

All had detectable RAVs at time of virologic

failure

Discontinuations due to adverse events: 1.5%

Most common adverse events

Headache, fatigue, diarrhea, nausea, asthenia

Manns M, et al. J Hepatol. 2014;60(suppl 1):S524-S525. Abstract O166.

Kao J-H, et al. J Hepatol. 2014;60(suppl 1):S527-S528. Abstract P1300.

0

20

40

60

80

100

SV

R12 (

%)

90%

82%

Treatment- Naïve

Prior PR Partial/Null Responder

PR Ineligible/ Intolerant

82%

Treatment-naive pts with GT1 HCV and

cirrhosis (N = 123)

MK-5172 + MK-8742 + RBV (n = 31)

MK-5172 + MK-8742 (n = 29)

MK-5172 + MK-8742 + RBV (n = 32)

Wk 12

MK-5172 100 mg once daily; MK-8742 50 mg once daily, RBV 1000-1200 mg divided twice daily.

C-WORTHY: MK-5172 + MK-8742

RBV

in GT1 Cirrhotics and Null Responders

Interim results from a randomized phase IIb trial

Primary endpoint: SVR12

Lawitz E, et al. EASL 2014. Abstract O61

Pts with GT1 HCV and null response

to pegIFN/RBV (N = 130)

MK-5172 + MK-8742 + RBV (n = 31)

MK-5172 + MK-8742 (n = 33)

Wk 18

MK-5172 + MK-8742 (n = 31)

MK-5172 + MK-8742 + RBV (n = 33)

MK-5172 + MK-8742 (n = 32)

C-WORTHY: Interim Results in Ttment -

Naive Cirrhotic Pts and Null Responders

Lawitz E, et al. EASL 2014. Abstract O61

28/ 31

28/ 29

30/ 31*

29/ 30*

*Excludes patients who have not yet reached SVR4 time point.

30/ 32

30/ 33

32/ 32*

29/ 30*

SV

R4

-8 (

%)

100

80

60

40

20

0 Treatment-Naive Pts

With Cirrhosis Null Responders

± Cirrhosis

12 wks + RBV 12 wks no RBV 18 wks + RBV 18 wks no RBV

90

97 97 91 94

100 97 97

HIV-ERADICATE: SOF/LDV en

coinfectados

Osinusi A, et al. EASL International Liver Congress, 2014. Abstract O14.

HIV/HCV Co-infected

HCV Genotype 1

Treatment-Naïve; F0-3

SOF: Sofosbuvir 400 mg daily

LDV: Ledipasvir 90 mg daily

ARV Untreated CD4 count stable and HIV RNA <500 copies OR CD4 count >500 cells/mm3

SVR12

ARV Treated CD4 count >100 cells/mm3 HIV RNA <40 copies Current ARVs ≥8 weeks

Currently SVR4

Regimen N(%)

Tenofovir/Emtricitabine plus

Efavirenz (EFV) 15 (41)

Raltegravir (RAL) 10 (27)

Rilpivirine (RPV) 8 (21)

RPV/RAL 3 ( 8)

EFV/RAL 1 ( 3)

HIV-ERADICATE: SVR

100 100 100 100 100100 100 100

0

20

40

60

80

100

HC

V R

NA

< L

LQ

, %

pa

tie

nts

Wk 8 EOT

13 37

SVR4 SVR12 SVR8

ARV Treated

ARV Untreated

13 30 12 22 10 10

Interim Results

Osinusi A, et al. EASL International Liver Congress, 2014. Abstract O14.

No clinically significant

changes in HIV RNA during

HCV treatment

One patient with transient HIV

viral breakthrough

Missed ARV for 4 days

Re-suppressed on the

same regimen

ARV Untreated (n=13)

ARV Treated (n=37)

C-WORTHY: MK-5172/ MK-8742

RBV

Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O63.

MK-5172 MK-8742 + RBV

0 12 24

HIV/HCV Co-infected

HCV Genotype 1

Non-cirrhotic

SVR12

SVR12 MK-5172 MK-8742 No RBV

Stable on raltegravir + two NRTIs for 8 weeks prior to enrollment

ART dose modification not permitted during 8 weeks preceding

enrollment unless dose modification due to tolerability failure

CD4 >300 cells/mm3

Undetectable HIV RNA for 24 weeks

C-WORTHY: MK-5172/ MK-8742

RBV

Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O63.

HC

V R

NA

< L

LQ

, %

pati

en

ts

Week 4 Week 8 Week 12 SVR4

No RBV + RBV Interim Results

100 100 10097

100

90 90 90

0

20

40

60

80

100

29 30 29 30 30 29 29 29

Cost per SVR with TVR or BOC[1,2]

~ $173,000-$189,000

Increased to ~ $257,000-$332,000 in cirrhotics

Estimates

(GT 1 IFN ineligible/intolerant)

SOF/RBV (24 Wks)

SOF/SIM (12 Wks)

Cost per regimen, $ 169,000 150,000

SVR rate, % 52-84 89-100

Base case cost per SVR, $ 244,000 165,000

Costo comparativo de una SVR

Hagan LM, et al. Hepatology. 2014;60:37-45.

El camino del tratamiento del VHC

Terapia triple

PI actuales

P/R

No acceso

• Baja eficacia en G1 (40 – 45%)

• Más baja en VHC/VIH (15-30%)

• Mínima con CV alta, IL28 TT

• Mínima en retratamiento

• Eficacia en G1 (+/-70%)

• Similar VHC/VIH (+/-65%)

• Eficaz con CV alta, IL28 TT

• Similar en relapsers

• Eficacia en G1 (+/-100%)

• Similar VHC/VIH (+/-100%)

• Eficaz con CV alta, IL28 TT

• Similar en relapsers, partial y null

• Simplicidad y tratamiento corto

• Mínimas RAM e interacciones

• Uso en F4 y transplante

DAA (STR)

IFN/RBV free,

short duration,

pangenotypic,

very tolerable,

few DDIs

1-2 DAA + RBV

IFN free,

more tolerable,

fewer DDIs

Resistencia

Costos

El futuro del tratamiento de VHC

Eficacia superior al 90 – 95%

Similar eficacia en cirrosis, fracaso previo, IL28, coinfección VIH

Mínimos efectos colaterales y DDI

Tratamientos coformulados sin IFN y sin RBV

Tratamientos acortados a 8 – 12 semanas ¿excepto en cirrosis - null?

Costos: > US$ 150.000 ¿con acceso en países de menores recursos?

Tratamiento universal si se logra acceso