1. No category

Tratamiento en los fracasos a antivirales de segunda
generación
Jose Luis Calleja
Profesor Titular de Medicina
Hospital Universitario Puerta de Hierro
Madrid
2012
Agenda
• Fracaso de los diferentes regímenes
– Impacto y persistencias de las resistencias
• Evidencia cientifica de eficacia en
retratamiento
• Recomendaciones de las Guias
• Conclusiones
EVIDENCIAS FRACASOS SOF+SMV
Estudio Fase 2: COSMOS
Lawitz AASLD 2013
EVIDENCIAS FRACASOS SOF+SMV
Estudio Fase 2: COSMOS
Lawitz EASL 2014
EVIDENCIAS FRACASOS SOF+SMV
Estudio vida real: TARGET
44/357 (12,3%)
Jensen AASLD 2014
Cohort of patients with treatment start on or before 4/15/14 ; BLOQ=Below Level of Quantitation;
SOF Containing Regimens
G3
G3
G3
G3
SOF + DCV: ALLY-3
•PEG + RBV
•PEG + RBV + SOF
•SOF + RBV
•SOF + DCV
GT 3; n=150
Study Week
⸗
SOF 400 mg + DCV 60mg QD 24w
0
12
24
36
9/13
32/34
11/19
73/75
DCV, daclatasvir; SOF, sofusbuvir; LLOQ, TD or TND, lower limit of assay quantitation, target detected or target not detected.
Nelson DR, et al. AASLD 2014. Oral LB-3
ATU Genotype 3
■ Most GT 3-infected patients were:
̶
̶
̶
̶
male (75%)
HCV mono-infected (83%)
cirrhotic (77%)
and treatment experienced (73%)
■ Median baseline platelet count: 118.5 x 109/L (range: 31–387)
■ Median baseline albumin: 39.0 g/L (range: 13–56)
Hezode C, et al. EASL 2015; Poster LP05
7
SVR4 Rates With DCV + SOF ± RBV By
Treatment Duration
12 Weeks
24 weeks
22/29
52/59
Cirrhotic
patients
11/12
5/6
Non-cirrhotic
patients
■ Treatment discontinuations were related to adverse events (1 patient),
death (2 patients), or patient decision (1 patient)
Hezode C, et al. EASL 2015; Poster LP05.
8
ALLY-1: Multicenter, Open-Label Phase 3 Study
Advanced cirrhosis
N = 60
DCV 60 mg QD +
SOF 400 mg QD + RBV
Follow-up
Post-liver transplant
N = 53
DCV 60 mg QD +
SOF 400 mg QD + RBV
Week 0
Week 12
Week 24
SVR12a
Week 36
■ Primary endpoint: SVR12 in GT1 in each cohort
■ 12 weeks of treatment: DCV 60 mg + SOF 400 mg + RBV
– RBV initially 600 mg/day, adjusted to 1000 mg/day based on Hgb levels and CrCl
■ Advanced cirrhosis patients with treatment interrupted by liver transplantation
could receive an additional 12 weeks of treatment immediately post-transplant
a
HCV RNA < lower limit of assay quantitation (LLOQ) at posttreatment Week 12 by Roche HCV COBAS TaqMan Test v2.0 (LLOQ 25 IU/mL).
9
Baseline Disease Characteristics by Child-Pugh Class
Advanced cirrhosis cohort
Parameter
Ascites present, n (%)
Encephalopathy present, n (%)
Native MELD score, n (%)a
< 10
10–15
16–20
21–25
> 25
Albumin, median (range) g/dL
INR, median (range)
T bilirubin, median (range) mg/dL
Platelets, median (range) × 109
cells/L
α-fetoprotein, median (range) ng/mLb
a Entry
criteria: MELD scores 8–40.
b Included 6 HCC patients: 1 CP A, 2 CP B, 3 CP C
Class A
N = 12
Class B
N = 32
Class C
N = 16
0
2 (17)
21 (66)
19 (59)
16 (100)
16 (100)
7 (58)
5 (42)
0
0
0
3.7 (3.0–4.3)
1.2 (1.1–1.4)
0.9 (0.4–1.7)
7 (22)
20 (63)
5 (16)
0
0
0
3 (19)
9 (56)
3 (19)
1 (6)
3.2 (2.6–4.4)
1.4 (1.0–1.9)
1.6 (0.6–4.4)
2.5 ( 2.0–3.4)
1.7 (1.2–3.9)
3.0 (1.1–6.4)
94 (41–179)
86 (35–182)
72 (35–147)
13.0 (3.4–49.6)
13.3 (1.8–86.2)
7.7 (1.8–149)
10
SVR12 by CohortSVR12 by Cohort
GT 1 (Primary Endpoint)
SVR12, %a
All Patients
Advanced
cirrhosis
Post-transplant
Advanced
cirrhosis
Post-transplant
■ In a regression analysis, no difference by gender, age, IL28B, or HCV RNA
in the advanced cirrhosis cohort with GT 1
a
HCV RNA < LLOQ (25 IU/mL); error bars reflect 95% confidence intervals.
11
SVR12 by Cohort
Patients Without SVR12
SVR12, %a
All Patients
9 relapses
1 HCV RNA
detectable at
end of treatment
3 relapses
Advanced
cirrhosis
Post-transplant
■ Patients with relapse are being retreated with DCV + SOF + RBV for 24 weeks
a
HCV RNA < LLOQ (25 IU/mL); error bars reflect 95% confidence intervals.
12
Resistance Analyses
Baseline resistance polymorphisms
■ NS5A-28, -30, -31, or -93 polymorphisms detected in 22 of 112 patients
– 82% (18/22) achieved SVR12
■ 10/14 in cirrhosis cohort; 8/8 in post-transplant cohort
– 90% (81/90) without NS5A polymorphisms achieved SVR12
■ 39/45 in cirrhosis cohort; 42/45 in post-transplant cohort
■ No NS5B-S282 variants detected at baseline or failure
NS5A resistance-associated variants in patients with virologic failure
Advanced cirrhosis
Post-transplant
10
3
NS5A RAVs at baseline, n/Na
4/10
0/3
NS5A RAVs at failure, n/Na
10/10
3/3
Virologic failures, N
a Assessed by
population-based sequencing.
13
Long-Term Persistence of HCV NS5A
Variants After Treatment With
NS5A Inhibitor Ledipasvir
David Wyles1, Alessandra Mangia2, Wendy Cheng3, Stephen Shafran4,
Christian Schwabe5, Wen Ouyang6, Krishna Chodavarapu6,
John McNally6, Brian Doehle6 , Evguenia Svarovskaia6, Michael D.
Miller6, Hongmei Mo6, Hadas Dvory-Sobol6
1University
of California San Diego, California, USA; 2Casa Sollievo della Sofferenza Hospital, San
Giovanni Rotondo, Italy; 3Royal Perth Hospital, Western Australia, Australia; 4University of Alberta,
Edmonton, Canada; 5Auckland Clinical Studies Ltd, Auckland, New Zealand;
6Gilead Sciences, Inc., Foster City, California, USA
EASL 2015, Vienna
Objectives
♦ To characterize NS5A RAVs in patients who failed
HCV treatment with ledipasvir (LDV) in the absence SOF
Quantify
– Proportion of patients with any NS5A RAV over time
Characterize
– Change in number and type of NS5A RAVs detected in any
given patient over time
15
Study Design
Sequence Registry Study
LDV + VDV + TGV
+ RBV (n=50)
LDV ±VDV ±TGV
+ PEG + RBV (n=26)
BL
FU-12
FU-24
FU-36
FU-48
FU-96
Plasma samples for sequence analysis
♦ Patients who did not achieve SVR in Gilead studies evaluating
direct-acting antiviral (DAA) regimens including LDV but not SOF
were enrolled in a 3-year registry study
♦ Plasma samples for sequence analysis were collected at baseline
and follow-up Weeks 12, 24, 36, 48, and 96
TGV, tegobuvir (GS-9190); VDV, vedroprevir (GS-9451).
16
Methods
♦ Sequencing analysis
– Population sequencing performed on sample from the parent study
– Deep sequencing using the MiSeq platform was used for all
samples
– 1% detection threshold was used for identification of variants
♦ NS5A RAVs at positions 24, 28, 30, 31, 32, 58, 93 that confer
>2.5-fold reduced susceptibility to LDV in vitro were included in
the analysis
17
Patients With NS5A RAVs (%)
Proportion of Patients With Any NS5A RAVs
at More Than 1%
62/63
Parent
Study
58/58
42/43
45/45
52/55
50/58
Registry Study
♦ NS5A RAVs persisted in majority of patients for 96 weeks
18
Efficacy of the 3D Regimen
In phase 3 trials, the recommended regimen* of 3D ± RBV achieved an
SVR rate of 97% across a broad range of HCV GT1a and GT1b patients
•
GT1a
Virologic Failure Rate %
(n/N)
GT1b
No Cirrhosis
3D + RBV
Cirrhosis
3D + RBV
No Cirrhosis
3D
Cirrhosis
3D + RBV
2.4 (14/593)
3.3 (4/121)
0 (0/301)
1.5 (1/68)
– 19 (18 GT1a, 1 GT1b) of 1083 patients (1.8%) receiving 3D
recommended regimens experienced virologic failure; breakthrough or
relapse
– Pooled resistance analysis included 2510 patients in Phase 2 and 3 trials
that received the 3D regimen irrespective of dose or duration of treatment
•
67 GT1a and 7 GT1b failures (2.9% of total population)
*3D without RBV for GT1b noncirrhotic patients, 3D+ RBV for GT1a and all cirrhotic patients, 12 week treatment
duration for all except GT1a cirrhotic patients who receive 24 weeks
Krishnan P., et al. EASL 2015
Pooled Analysis: Resistance-Associated Variants that Emerged
in the 3D ± RBV Regimens in Phase 2 and 3
Target
Resistance-Associated Variants
NS3
At any NS3 amino acid position:
36, 43, 55, 56, 132, 155, 156, 168
R155K
D168 any (A/F/H/I/L/N/T/V/Y)
D168V
NS5A
NS5B
3D (All Pooled)
N = 2510
Number of Virologic
Failures N (%)
GT 1a
GT 1b
N = 67
N=7
52(78%)
4 (57%)
9 (13%)
43 (64%)
35 (52%)
4 (57%)
3 (43%)
At any NS5A amino acid position:
28, 30, 58, 93
48 (72%)
2 (29%)
M28A/T/V
Q30E/K/R
Y93H
20 (30%)
29 (43%)
-
2 (29%)
At any NS5B amino acid position:
316, 414, 446, 553, 554, 556, 558, 559, 561
39 (59%)
2 (29%)
C316Y
M414I/T
S556G/R
2 (3%)
3 (5%)
23 (35%)
1 (14%)
1 (14%)
1 (14%)
Krishnan P., et al. EASL 2015
Persistence of TEVs in NS3 in PTV/r-Containing
Regimens (GT1a)
Non-Cirrhotics
n/N (%)
2D ± RBV
Time
window
Cirrhotics
n/N (%)
3D ± RBV
3D + RBV
All PTV/rContaining
Regimens
n/N (%)
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
TEVs
(any)
6/19
(32)
1/17
(6)
19/37
(51)
3/32
(9)
8/11
(73)
1/8
(13)
31/67
(46)
5/57
(9)
D168
(any)
4/16
(25)
0/16
(0)
11/30
(37)
1/30
(3)
6/9
(67)
1/7
(14)
21/55
(38)
2/53
(4)
R155K
2/5
(40)
1/5
(20)
6/6
(100)
1/2
(50)
2/2
(100)
LTFU
10/13
(77)
2/7
(29)
2D = PTV/r + (DSV or OBV); PTW = post-treatment Week; LTFU = lost to follow-up
•
•
•
•
Treatment duration or regimen did not affect rate of decline of TEVs in NS3
TEVs in NS3 declined to a prevalence of 9% at PTW48
The most common TEV selected by PTV was D168V, which was less persistent than
the R155K variant that was infrequently detected with PTV regimens (more common
with simeprevir)
Among patients experiencing virologic failure with the recommended regimen, 60% had
TEVs at PTW24 and none had TEVs at PTW48 in NS3
Krishnan P., et al. EASL 2015
Persistence of TEVs in NS5A in OBVContaining Regimens (GT1a)
Non-Cirrhotics
n/N (%)
2D ± RBV
Time
window
Cirrhotics
n/N (%)
3D ± RBV
3D + RBV
All OBV-Containing
Regimens
n/N (%)
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
TEVs
(any)
13/13
(100)
10/10
(100)
42/42
(100)
31/32
(97)
13/15
(87)
8/9
(89)
68/70
(97)
49/51
(96)
M28V/T
6/6
(100)
5/5
(100)
20/21
(95)
14/14
(100)
6/6
(100)
2/2
(100)
32/33
(97)
21/21
(100)
Q30E/K/
R
7/8
(88)
5/6
(83)
23/24
(96)
15/16
(94)
8/9
(89)
5/6
(83)
38/41
(93)
25/28
(89)
2D = PTV/r + OBV; PTW = post-treatment Week
• Treatment duration or regimen did not affect rate of
decline of TEVs in NS5A
• Predominant TEVs at NS5A amino acid positions M28
and Q30 remained detectable at similar levels at PTW24
and 48
Krishnan P., et al. EASL 2015
Persistence of TEVs in NS5B in DSV-Containing
Regimens (GT1a)
Non-Cirrhotics
n/N (%)
2D ± RBV
Time
window
Cirrhotics
n/N (%)
3D ± RBV
3D + RBV
All DSV-Containing
Regimens
n/N (%)
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
PTW24
PTW48
TEVs
(any)
3/6
(50)
4/6
(67)
21/28
(75)
15/23
(65)
9/10
(90)
3/7
(43)
33/44
(75)
20/35
(57)
S556G
2/2
(100)
1/2
(50)
20/22
(91)
14/17
(82)
5/6
(83)
2/3
(67)
27/30
(90)
17/22
(77)
Other
1/4
(25)
1/4
(25)
1/12
(8)
1/9
(11)
5/5
(100)
0/4
(0)
7/21
(33)
3/18
(17)
2D = PTV/r + DSV; PTW = post-treatment Week; Other = M414T, A553D/T/V, G554S, G558R, D559G/N
•
Treatment duration or regimen did not affect rate of decline of TEVs in
NS5B
•
Predominant TEV S556G remained detectable at PTW24 and 48
•
Minor NS5B TEVs A553D/T/V, G554S, G558R, D559G/N declined through
PTW24 and 48
Krishnan P., et al. EASL 2015
Importancia de las resistencias
♦ La mayor parte de los pacientes con fracaso virológico
desarrollan resistencias
♦ Las resistencias en NS3 desaparecen en poco tiempo, pero las
resistencias al NS5a y b persisten en el tiempo
♦ La aparicion del polimorfismo S262T que confiere resistencia a
sofosbuvir es excepcional
♦ El impacto de las resistencias NS5a en la RVS es variable:
– Basales o desarrolladas durante el tratamiento
– Tipo de resistencias
– Número de resistencias
Agenda
• Fracaso de los diferentes regímenes
– Impacto y persistencias de las resistencias
• Evidencia cientifica de eficacia en
retratamiento
• Recomendaciones de las Guias
• Conclusiones
Successful Retreatment With
Sofosbuvir-containing Regimens for
HCV Genotype 2 or 3 Infected Patients who
Failed Prior Sofosbuvir Plus Ribavirin Therapy
Rafael Esteban1, Lisa Nyberg2, Jay Lalezari3, Liyun Ni4, Brian Doehle4, Bittoo
Kanwar4, Diana Brainard4, GM Subramanian4, William T. Symonds4, John G.
McHutchison4, Maribel Rodriquez-Torres5, Stefan Zeuzem6
1Vall
d’Hebron Hospital, Barcelona, Spain; 2Kaiser Permanente, San Diego, CA, USA;
3Quest Clinical Research, San Francisco, CA, USA; 4Gilead Sciences, Inc., Foster City, CA, USA;
5Fundacion de Investigacion, San Juan, Puerto Rico; 6JW Goethe University Hospital, Frankfurt, Germany
International Liver Congress 2014, London, UK
Results: On Treatment Viral Response and
SVR 12
28/28 50/50
28/28 50/50
24/26
25/40
♦ Relapse accounted for all virologic failures
Error bars represent 95% confidence intervals.
27
Results: GT 3 SVR12 by Cirrhosis Status
13/14
7/8
17/23
7/15
28
EVIDENCIAS EN RESCATE
ELECTRON-2
LONESTAR
EVIDENCIAS EN RESCATE
ELECTRON-2 Results, Prior Sofosbuvir-Treated GT 1 Patients
Re-treatment
SOF+RBV 12 wk
Prior Null
Responders
SOF+RBV 12 wk
Treatment Naïve
n=4
SVR12 (%)
n=6
n=1
GS-9669 + SOF
+RBV 12 wk
Treatment Naïve
•
n=8
LDV/SOF +RBV
6 wk
Treatment Naïve
All 19 previous SOF-regimen failures had relapsed
Gane EASL 2014
19/19
19/19
EVIDENCIAS EN RESCATE
98%
98% SVR
100% SVR
88%
No NS5A RAVs
at baseline
12%
NS5A RAVs
n=44/50*
n=6/50
n=43/44
*1 patient’s baseline results were not available.
Wyles D et al. AASLD 2014 Abstract #
•
No patients had SOF-associated variant, S282T, detected at baseline
–
2 patients had NS5B treatment-emergent variant# L159F at baseline and
achieved SVR
31
EVIDENCIAS EN RESCATE
LONESTAR
Lawitz aasld 2013
Retreatment of Patients Who Failed 8 or
12 Weeks of Ledipasvir/Sofosbuvir-Based
Regimens With Ledipasvir/Sofosbuvir for
24 Weeks
Eric Lawitz1, Steven Flamm2, Jenny C. Yang3, Phillip S. Pang3, Yanni Zhu3,
Evguenia Svarovskaia3, John G. McHutchison3, David Wyles4,
Paul Pockros5
1Texas
Liver Institute, University of Texas Health Science Center, San Antonio, Texas,
USA; 2Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA;
3Gilead Sciences, Inc., Foster City, California, USA;
4University of California, San Diego, California, USA;
5Scripps Clinic, La Jolla, California, USA
EASL 2015, Vienna
Study Design
GT 1 Retreatment
Wk 0
Wk 12
Wk 24
Wk 36
SOF failures (n=51)
LDV/SOF + RBV
LDV/SOF failures
(n=41)
LDV/SOF
SVR12
SOF failures (advanced
LDV/SOF + RBV
SVR12
liver disease)
1. Wyles D, et al. AASLD 2014. Abstract 235.
98%
SVR121
SVR12
Demographics and Baseline Characteristics
GT 1 Retreatment
LDV/SOF 24 Weeks
N=41
Mean age, y (range)
58 (35–71)
Male, n (%)
34 (83)
Black/African American, n (%)
10 (24)
IL28B non-CC, n (%)
38 (93)
GT 1a, n (%)
34 (83)
Mean HCV RNA, log10 IU/mL (range)
Cirrhosis, n (%)
Presence of NS5A RAVs
6.2 (4.5–7.4)
19 (46)
15 (79)
Prior HCV treatment, n (%)
LDV/SOF ± RBV
33 (80)
LDV/SOF + GS-9669
8 (20)
Prior HCV treatment duration, n (%)
8 weeks
Presence of NS5A RAVs
12 weeks
Presence of NS5A RAVs
30 (73)
19 (63)
11 (27)
11 (100)
Results: On-Treatment Viral Kinetics and SVR
HCV RNA <LLOQ (%)
GT 1 Retreatment
13/41
39/41
41/41
40/41
30/41
29/41
♦ One patient experienced on-treatment breakthrough at Week 16
EOT, end of treatment. Error bars represent 95% confidence intervals.
36
SVR12 (%)
SVR12 by Subgroup
GT 1 Retreatment
15/22
14/19
No
No
Yes
Yes
Cirrhosis
24/30
5/11
11/11
No
Prior Treatment
Duration
18/30
Yes
Baseline NS5A RAVs
♦ All 11 patients without NS5A RAVs received 8 weeks of prior treatment
37
SVR12 (%)
SVR12 by Baseline NS5A RAVs
GT 1 Retreatment
11/1
1
11/16
7/14
Number of NS5A RAV(s)
*M28T (n=1).
5/5
4/5
2/6
Type of Single NS5A RAV
38
Conclusions
GT 1 Retreatment
♦ 71% of patients who failed prior LDV/SOF-containing regimens
achieved SVR12 when retreated with LDV/SOF for 24 weeks
♦ The presence of baseline NS5A RAV(s), which was more likely
to develop with longer prior LDV/SOF treatment, was
associated with virologic failure
♦ Emergence of S282T was observed in 3 of 12 virologic failure
patients
♦ Retreatment with LDV/SOF is feasible in patients who have
failed prior LDV/SOF-based regimens
39
Agenda
• Fracaso de los diferentes regímenes
– Impacto y persistencias de las resistencias
• Evidencia cientifica de eficacia en
retratamiento
• Recomendaciones de las Guias
• Conclusiones
RESCATE ¿QUÉ DICEN LAS GUÍAS?
Recommended Regimens for TreatmentExperienced GT1 HCV Pts
Population
Noncirrhotic
Compensated Cirrhotic
Regimen
Duration,
Wks
LDV/SOF
12
Regimen
Duration,
Wks
Prior PegIFN/RBV
 GT1a or 1b
 GT1a or 1b
LDV/SOF
24
LDV/SOF + RBV
12
 GT1a
OMV/PTV/RTV + DSV + RBV
12
OMV/PTV/RTV + DSV + RBV
24
 GT1b
OMV/PTV/RTV + DSV
12
OMV/PTV/RTV + DSV + RBV
12
SMV + SOF ± RBV
12
SMV + SOF ± RBV
24
LDV/SOF ± RBV
24
LDV/SOF
24
LDV/SOF + RBV
12
 GT1a or 1b
Prior SOF
 GT1a or 1b
Defer therapy*
Prior PI
 GT1a or 1b
 GT1a or 1b
LDV/SOF
12
*Based on limited available data, pts without advanced fibrosis and without an urgent need for HCV treatment should defer
antiviral therapy pending additional data or consider clinical trial.
EASL Guidelines 2015
 Sofosbuvir + Riba
– Genotipo 1 :
• SOF/LED , Abbvie y SOF/DAC
– Genotipo 2 y 3 : SOF/DAC
r
– Genotipo 4 : SOF/LED, Abbvie 2D y SOF/DAC
 Sofosbuvir + Simeprevir
– SOF/LED y SOF/DAC
EASL Guidelines 2015
• SOF + Inh NS5A
– Sofosbuvir + Simeprevir
– Genotipo 2 y 3 : SOF/DAC 24 semanas o 12 sem
con RIBA
• Abbvie 3D
– SOF /DAC y SOF /LED 24 semanas con RIBA
HCV Reinfection in
Phase 3 Studies of Sofosbuvir
Christoph Sarrazin,1 Vasily Isakov,2 Evguenia Svarovskaia,3 Ross Martin,3
Krishna Chodavarapu,3 Charlotte Hedskog,3 Diana Brainard,3 Michael Miller,3
Hongmei Mo,3 Jean-Michel Molina,4 Mark S. Sulkowski5
1J.
W. Goethe-University Hospital, Frankfurt am Main, Germany; 2Institute of Nutrition, Moscow,
Russia; 3Gilead Sciences, Inc., Foster City, California, USA; 4University of Paris Diderot, Paris,
France; 5Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
EASL 2015, Vienna
Concordance of SVR12 and SVR24 in SOF
Clinical Studies
Concordance
99%
Patients achieved SVR12
N=3004
Patients achieved SVR24
n=2992
Did not achieve SVR24
n=12
Full-length NS5B successfully
deep sequenced
n=10
Only short NS5B fragment
sequenced due to low HCV viral load
n=2
45
Investigation of Relationship Between
Baseline and Rebound Virus
Genotype or subtype at baseline and at failure
Same
Different
Phylogenetic analysis
Related
Distantly related
Not related
Phylogenetic analysis
of quasispecies
(baseline, FU-24)
Mixed
Late relapse
Different
Reinfection
46
Phylogenetic Analyses
Genotype
Patient
Study
Baseline
Post-Treatment
Phylogenetic Distance
1
PHOTON-2
4d
1a
Not related*
2
PHOTON-1
1a
1a
Not related*
3
PHOTON-2
1a
1a
Not related*
4
GS-US-334-0119
1b
1b
Not related*
5
FUSION
3a
3a
Not related†
6
PHOTON-2
1a
1a
Distantly related
7
FUSION
3a
3a
Distantly related
8
PHOTON-1
3a
3a
Closely related
9
VALENCE
3a
3a
Closely related
10
VALENCE
3a
3a
Closely related
11
FISSION
3a
3a
Closely related
12
PHOTON-2
3a
3a
Closely related†
*Similar results were obtained for NS3, NS5A, and NS5B when sequences were available.
†Short fragment NS5B sequencing only, due to low viral load.
47
CONCLUSIONES
• Es imprescindible generar nueva evidencia en
pacientes no respondedores a los diferentes
regímenes orales
• Parece razonable ser conservador en las
pautas en pacientes con riesgo de recidiva
• Mientras tanto:
– No respuesta a SOF + IP : SOF+ Inh NS5a
– No respuesta a SOF + Inh NS5a:
• Genotipo 1 y 4 : SOF + IP
• Otros genotipos : Alargar el tratamiento y
añadir RIBA