![Page 1: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/1.jpg)
1
in partnership
with
Medical Centre for Infectious Diseases
Berlin (MIB), Germany
Dr Patrick Ingiliz
Pre-conference Clinical Course
in partnership
with
COMPETING INTEREST OF FINANCIAL VALUE > £1,000
Statement
I have done educational presentations and advisory boards for
Abbvie, BMS, Gilead, and MSD
Date: December 2015
Medical Centre for Infectious Diseases
Berlin (MIB), Germany
Dr Patrick Ingiliz
Pre-conference Clinical Course
![Page 2: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/2.jpg)
2
Treatment of Hepatitis C: Who?When?How?
Patrick Ingiliz, Berlin
FIVE NATIONS CONFERENCE
on
HIV and Hepatitis
8–9 December 2014
Queen Elizabeth II Conference Centre
LONDON · UK
HCV is a Progressive Disease with Serious Sequelae
Adapted from Chen SL, Morgan TR. Int J Med Sci 2006;3:47–52
*20–30% of individuals are symptomatic; HCC: hepatocellular carcinoma
Permission is granted to use this figure; original source:
Chen SL, Morgan TR. The Natural History of Hepatitis C Virus (HCV) Infection.
Int J Med Sci 2006; 3(2):47-52. http://www.medsci.org/v03p0047.htm
Acute
infection*
Chronic
infection
75–85%
Clearance of
HCV RNA
15–25%
Extrahepatic manifestations
Cirrhosis
10–20%
over 20 years
HCC
1–4% per year
Decompensated
cirrhosis
5-year survival rate 50%
Risk of decompensation increases
from 5% (1 year) to 30% (10 years)
from the diagnosis of cirrhosis
![Page 3: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/3.jpg)
3
Effective treatment of HIV infection reduces fibrosis risk in HIV/HCV-coinfected patients
Created from Macias J, et al. Hepatology 2009;50:1056–63.
Predictive factors of fibrosis progression (≥1 stage) (multivariate analysis)
RR (95% CI)=relative risk (95% confidence interval); ETR=end-of-treatment response; HAART=highly active antiretroviral therapy; *Undetectable HIV RNA in ≥70% determinations during the follow up.
Age, years
HAART during the follow-up
Undetectable HIV viraemia*
CD4 cell counts change
Genotype 3
Baseline ALT, IU/mL
Baseline necroinflammatory activity
Time between liver biopsies
Response to anti-HCV treatment
0.90
0.72
0.028
0.87
0.72
0.58
0.009
0.011
0.023
Relative risk (95% CI)
0.5 1.0 1.5 2.0 2.5 3.0
p multivariate
Data collected from 135 coinfected patients with 2 liver biopsies >1 year apart.
Specimens were centrally read and scored blindly by 2 independent pathologists using the Scheuer classification.
(≥37 vs <37)
(Yes vs No)
(Yes vs No)
(Per 25 cell increase)
(Yes vs No)
(≥66 vs <66)
(L2–4 vs L0–1)
(Per 1 year increase)
(ETR vs no ETR)
ART and hepatic decompensation in HCV/HIV vs. HCV alone
Lo Re III, V, et al. Ann Intern Med 2014; 160: 369
![Page 4: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/4.jpg)
4
SVR is associated with a reduction of liver-related mortality and HCC
van der Meer AJ, et al. JAMA. 2012; 308(24):2584-2593.
retrospective multicenter study, n=530, HCV mono
SVR is associated with a reduction of overall mortality: meta-analysis of 129 studies, n=29,269
Hill et al., AASLD 2014
![Page 5: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/5.jpg)
5
Estimated prevalence of liver cirrhosis
Wedemeyer et al., JVH 2014
Estimation: SVR rate 90%, treatment rate doubled
Rx as Prevention - Modelling treatment impact in IDU populations - seven UK cities with scale-up with DAAs
Martin NK, et al. C-Hep, Berlin 2014.
Baseline in 2014
2024, no scale-up, ITT SVR with PEG-IFN + RBV
2024, scale-up to 26/1000 annually with IFN-free DAAs (all genotypes) in 2016
HC
V c
hro
nic
pre
vale
nce a
mo
ng
PW
ID (
%)
0
10
20
30
40
50
60
70
80
90
100
Bristol East
London
ManchesterNottingham Plymouth Dundee North
Wales
![Page 6: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/6.jpg)
6
Reinfection – an alarming reality!
Ingiliz et al., EASL 2014
553 patients from 7 NEAT centers
with cured acute HCV since 6/2001
141 with at least one reinfection (25.5%)
1509 patient-years of FU, median 2.1 years
Incidence rate: 7.82/100 patient-years
Treated patients: 7.9/100 patient years
Spontaneous clearers: 3.3/100 patient-
years
0
20
40
60
80
100
IFN
6 mo
IFN
12 mo
IFN+RBV
6 mo
IFN+RBV
12 mo
PEG
12 mo
PEG+RBV
12 mo
PI+PEG
+RBV
6-12 mo
LDV/SOF/RBV
AbbVie 3D
5172/8472
12 weeks
68-75
54-56
3942
34
16
6
90
1986 1998 20022001 2011 2013
SV
R R
ate
(%
)
*Year of data presentation at EASL 2014 and publication in NEJM
Adapted from Strader DB, et al. Hepatology 2004;39:1147-71. INCIVEK [PI]. Cambridge, MA: Vertex Pharmaceuticals; 2013. VICTRELIS [PI]. Whitehouse Station, NJ: Merck & Co; 2014. Jacobson I, et al. EASL 2013. Amsterdam. The Netherlands. Poster #1425. Manns M, et al. EASL 2013. Amsterdam. The Netherlands. Oral #1413. Lawitz E, et al. APASL 2013. Singapore. Oral #LB-02; Afdhal N, et al. N Engl J Med 2014; 2014 Apr 12 ; Kowdley K, et al. N Engl J Med 2014; 2014 Apr 11
SMV+PEG
+RBV
6-12 mo
80-81
2014*
SOF+PEG
+RBV
3 mo
94-99
HCV Genotype 1 Treatment-Naïve Patients – improving SVRs
![Page 7: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/7.jpg)
7
EASL recommendations on treatment of hepatitis C
EASL recommendations April /easl-recommendations-on-treatment-of-hepatitis-c-summary.pdf2014 http://files.easl.eu
Newly diagnosed chronic
HCV infection
F2F3aF0F1a F4a
In general, treatment can be
deferred. Treatment with Peg/RBV and
DAA or 2/3 DAA +/- r based
regimen.
Treatment with Peg/RBV
and DAA if compensated
disease or 2/3 DAA +/- r
based regimen
Treatment should be
undergone in specialised
centres.
Management of newly diagnosed HIV-HCV coinfected
genotype-1 patients
Perform transient elastography and/or
serum marker and/or liver biopsy
aMetavir fibrosis score: F0=no fibrosis; F1= portal fibrosis, no septae;
F2= portal fibrosis, few septae, F3=bridging fibrosis, F4=cirrhosis.
Management of HIV/HCV Co-infected Patients (EACS 2014)
![Page 8: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/8.jpg)
8
3’UTR5’UTR Core E1 E2 NS2 NS4BNS3 NS5A NS5Bp7
Telaprevir
Boceprevir
Simeprevir
Asunaprevir
Paritaprevir
Grazoprevir
Daclatasvir
Ledipasvir
Ombitasvir
Elbasvir
GS-5816
Sofosbuvir
VX-135
IDX21437
ACH-3422
Dasabuvir
Beclabuvir
NS5B
NUC Inhibitors
NS3
Protease
Inhibitors
NS5A
Replication
Complex
Inhibitors
Ribavirin
NS5B
Non-NUC
Inhibitors
*Representative list modified from CCO.
PolymeraseProtease
Which drugs beyond PegRIBA?
3’UTR5’UTR Core E1 E2 NS2 NS4BNS3 NS5A NS5Bp7
Telaprevir
Boceprevir
Simeprevir
Asunaprevir
Paritaprevir
Grazoprevir
Daclatasvir
Ledipasvir
Ombitasvir
Elbasvir
GS-5816
Sofosbuvir
VX-135
IDX21437
ACH-3422
Dasabuvir
Beclabuvir
NS5B
NUC Inhibitors
NS3
Protease
Inhibitors
NS5A
Replication
Complex
Inhibitors
Ribavirin
NS5B
Non-NUC
Inhibitors
*Representative list modified from CCO.
PolymeraseProtease
....previr (PI)
....asvir (NS5A)
....buvir (Pol)
Which drugs beyond PegRIBA?
![Page 9: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/9.jpg)
9
HCV drug pipeline
Jan 2014
Sofosbuvir
May 2014
Simeprevir
Aug 2014
Daclatasvir
Nov 2014
STR Gilead
Sofosbuvir
Ledipasvir
Jan 2015
3D Abbvie
Ombitasvir
Paritaprevir
Dasabuvir
2016?SOF/GS-5816
2016?MSD-Worthy
Grazoprevir
Elbasvir
....buvir
2015?BMS-Unity
Daclatasvir
Asunaprevir
Beclabuvir
DAA combinations in 2015/2016
Gilead STR
(ION-1)1
3D Abbvie
(SAPPHIRE-I)2
BMS Unity3 DCV + SOF4 MSD
(C-WORTHY)5
1. Afdhal N, et al. NEJM 2014; Epub ahead of print. 2. Feld J, et al. EASL 2014, Abstract O60. 3. Everson GT, et al. CROI 2014,
Abstract 25. Available at: http://croi2014.org/sites/default/files/uploads/CROI2014_Final_Abstracts.pdf (Accessed May 2014).
4. Sulkowski M, et al. NEJM 2014;370:211–21. 5. Hezode C, et al. EASL 2014, Abstract O10. EASL abstracts available at:
http://www.ilc-congress.eu/#&panel1-1 (Accessed May 2014).
455/473 71/77 41/41 25/25211/214
SVR rates from different regimens in Phase II-III studies (genotype 1,
treatment naive, 12 weeks)
![Page 10: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/10.jpg)
10
Indications for HCV treatment in HIV/HCV co-infected patients are identical to those in HCV mono-infection (A1)
Same treatment regimens can be used in HIV/HCV patients as in patients without HIV infection, as the virological results of therapy are identical (A1)
EASL recommendations April 2014 http://files.easl.eu/easl-recommendations-on-treatment-of-hepatitis-c-summary.pdf
HCV/HIV co-infection: pegIFNα-free regimens GT-1
1. Molina J, et al. AIDS 2014, MOAB0105LB2. 2. Sulkowski M, et al. AASLD
2014. 3. Osinusi A, et al. EASL 2014, O14. 4. Sulkowski M, et al. AIDS 2014,
MOAB0104LB.
![Page 11: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/11.jpg)
11
SOF/LDV: GT1 and 4: 12 weeks (8-24) +/-RBV
GT 3: 24 weeks+ RBV (TE, F4)
22
SVR12 from VALENCE includes pooled analysis from all patients (treatment-naïve and –experienced) by genotype and duration of therapy*GT1 SVR24 of 75%; GT3 TE SVR24 of 88%
100
28/42
SV
R12 (%
)
90 89
0
20
40
60
80
100
NEUTRINO1
HCV
19102
HCV/HIV
GT 1
SOF + RBV + PegIFN
12 weeks
GT 1
SOF + RBV
24 weeks
68
76*
0
20
40
60
80
100
SPARE3
HCV
PHOTON-14
HCV/HIV
87/11417/25 95/112
85
PHOTON-26
HCV/HIV
GT 3
SOF + RBV
24 weeks
85
94*
0
20
40
60
80
100
VALENCE5
HCV
PHOTON-14
HCV/HIV
16/17212/250
PHOTON-26
HCV/HIV
89
94/106
GT 2
SOF + RBV
12 weeks
9388
0
20
40
60
80
VALENCE5
HCV
PHOTON-14
HCV/HIV
68/73 23/26
88
22/25
PHOTON-26
HCV/HIV
262/292 17/19
Photon 1 & 2: SOF + RBV Comparison HCV monoinfection and HIV/HCV coinfection trials
1. Lawitz E, et al. APASL 2013. Singapore. Oral #LB-02. 2. Rodriguez-Torres M, et al. IDWeek 2013; San Francisco, CA. Poster 714. 3. Osinusi A, et al. JAMA. 2013;310(8):804-811. 4. Naggie S, et al.
CROI 2014. Boston, MA. Oral #26. 5. Zeuzem S, et al. AASLD 2013. Washington, DC. #1085. 6. Molina JM, et al. IAS Melbourne Abstract MOAB0105LB
![Page 12: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/12.jpg)
12
Any remaining question on HCV treatment?
• How will study data translate into real-life?
• HCV non-genotype 1/HCV genotype 3?
• Ribavirin?
• Cirrhotics beyond CHILD A
• ESLD/LTX/ESRD?
• DDIs?
SOF/P/R
N=384
SOF/RBV
N=667
SOF/SMV
N=784
SOF/SMV/RBV
N=228
Safety and Efficacy of SOF-Containing Regimens for HCV
HCV-TARGET
Jensen, AASLD, 2014, Oral #45
Genotype 3
SOF/PegIFN/RBV
8.5%
SOF/RBV
91.5%
Genotype 2
SOF/PegIFN/RBV
0.9%
SOF/RBV
99.1%
Genotype 1
SOF/SMV/RBV
14.9%
SOF/PegIFN/RBV
23.1%
SOF/RBV
8.8%
SOF/SMV
53.1%
Real-world observational study of 2,063 patients treated with DAAs at academic (n=38) and community medical centers (n=15) in North America and Europe
Started Therapy HCV-TARGET 2.0
N=2063
![Page 13: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/13.jpg)
13
HCV-TARGET
n (%)
SOF+PegIFN+
RBV
n=384
SOF+SMV
±RBV
n=228
SOF+SMV
n=784
SOF+RBV
n=667
Total
n=2063
Completed treatment 332 (86.5) 189 (82.9) 663 (84.6) 429 (64.3) 1613 (78.2)
Ongoing treatment 41 (10.7) 32 (14.0) 101 (12.9) 205 (30.7) 379 (18.4)
D/C Prematurely* 11 (2.9) 7 (3.1) 20 (2.6) 33 (4.9) 71 (3.4)
AE 6 (1.6) 5 (2.2) 16 (2.0) 17 (2.5) 44 (2.1)
Death 1 (0.3) 2 (0.9) 6 (0.8) 3 (0.4) 12 (0.6)
140/164 269/303 44/54 168/187
GT 1 GT 2
12 Wk Regimens
SVR4/SVR12 Concordance: 94.4–98.2% PPV
Jensen, AASLD, 2014, Oral #45*Not all premature D/C are summarized. Full list available in final slides.
Safety and Efficacy of SOF-Containing Regimens for HCV
SOF-DAC for 12 weeks in GT 3
a Cirrhosis status determined in 141 patients by liver biopsy (METAVIR F4), FibroScan (> 14.6 kPa), or FibroTest score ≥
0.75 and APRI (aspartate aminotransferase to platelet ratio index) > 2.b Cirrhosis status for 11 patients was inconclusive (FibroTest score > 0.48 to < 0.75 or APRI > 1 to ≤ 2).
■ Among patients with cirrhosis, 34% (11/32) had baseline platelet counts <100,000/mm3
SV
R1
2,
%
PresentAbsent PresentAbsent PresentAbsent
Treatment-naive Treatment-experiencedOverall
Cirrhosisa,b
![Page 14: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/14.jpg)
14
Sofosbuvir / GS5816 +/- Ribavirin 12 weeks genotype 3
Pianko et al., AASLD 2014
3D: Paritaprevir/r/ombitasvir (150/100/25 mg QD) plus dasabuvir (250 mg BID)
RBV: 1000 or 1200 mg daily in 2 divided doses according to body weight
(<75 kg and ≥75 kg, respectively)
Day 0 Week 12 Week 24
Open-Label Treatment
SVR12
All patients followed
through
48 weeks post-treatment3D + RBV
(N = 208)
3D + RBV
(N = 172)
SVR12
Week 36
TURQUOISE-II: Study Design380 Patients with Cirrhosis, genotype 1
![Page 15: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/15.jpg)
15
SV
R1
2,
% P
ati
en
ts
12-Week 24-Week
0
20
40
60
80
100
96.591.8
191
208
166
172
TURQUOISE-II: Overall SVR12 Rates
LDV/SOF + RBV for HCV Patients with Decompensated Cirrhosis
108 patients randomized 1:1 to 12 or 24 weeks of treatment
Stratified by CTP class B [7-9] or C [score 10–12]*
Broad inclusion criteria:
No history of major organ transplant, including liver
No hepatocellular carcinoma (HCC)
Total bilirubin ≤10 mg/dL, Hemoglobin ≥ 10 g/dL
CrCl≥ 40 mL/min, Platelets > 30,000
RBV dosing: dose escalation, 600–1200 mg/d
SOLAR-1
Prospective, multicenter study of 12 or 24 weeks of LDV/SOF + RBV in TN and TE HCV GT 1 and 4 patients with CTP B (N=59) or CTP C (N=49) clinically decompensated cirrhosis
Wk 0 Wk 12 Wk 36Wk 24
SVR12N=53
SVR12N=55 LDV/SOF + RBV
LDV/SOF + RBV
*Patients with CTP scores 13-15 were excludedFlamm, AASLD, 2014, Oral #239
![Page 16: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/16.jpg)
16
Results: SVR12
SOLAR-1: LDV/SOF + RBV in Decompensated Cirrhosis
CTP B CTP C
SV
R12 (
%)
26/30 19/22 18/2024/27
Error bars represent 90% confidence intervals.
LDV/SOF + RBV 12 Weeks LDV/SOF + RBV 24 Weeks
SVR rates were similar with 12 or 24 weeks of LDV/SOF + RBV
Flamm, AASLD, 2014, Oral #239
ABT450rSubstrate for CYP 3A4, PgP,
OATP1B1/3
Weak inhibitor PgP/BCRP (gut),
?OATP1B1/3
MK-5172Substrate for CYP 3A4, PgP, ?
OATP1B1
Inhibits CYP 2C8, weak inhibitor
of UGT1A1, ? BCRPModerate
Simeprevir Substrate for CYP 3A4, PgPInhibits OATP1B1, MRP2
Mild inhibitor gut CYP 3A4, PgPModerate
MK-8742Substrate for CYP 3A4, PgP,
?OATP1B1weak inhibitor of UGT1A1 Moderate
Sofosbuvircathepsin A, esterases, kinases
PgP & BCRP substrate (parent)
Weak inhibitor of gut PgP &
BCRPLow
Daclatasvir Substrate for CYP 3A4, PgP Inhibits OATP1B1/3 & PgP Moderate
VICTIM of DDI PERPETRATOR of DDIDDI
potential
Dasabuvir(ABT-333)
Substrate of CYP 2C8 > 3A4 >
2D6,
Substrate of PgP, BCRP
Weak inhibitor of UGT1A1
Ombitasvir(ABT-267)
Substrate for PgP, BCRP
(CYP 3A4 )Weak inhibitor of UGT1A1
Moderate to
Significant
(RTV)
LedipasvirPrimarily excreted unchanged
(>98% faeces), PgP / BCRP
substrate
Weak inhibitor of PgP/BCRP,
?OATP1B1/3?Low
TLPTeleprevir Substrate for CYP 3A4, PgP
Inhibits CYP 3A4, PgP,
OATP1B1/2
? Protein binding
Significant
BoceprevirSubstrate for
aldoketoreductase,
CYP 3A4, PgP, BCRP
Inhibits CYP 3A4, PgP, OCT 1&2Significant
Slide courtesy of S Khoo, 2014
![Page 17: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/17.jpg)
17
DCV SOF SMV LDV
NRTIs
Lamivudi
ne
Emtricita
bine
Abacavir
Tenofovir
NNRTIs
Nevirapi
ne
Efavirenz 90
Etravirin
e
Rilpivirin
e
DCV SOF SMV LDV
HIV Protease Inhibitors
Lopinavir/r 30
Fosamprenavi
r/r 30
Atazanavir/r 30
Atazanavir 60
Darunavir/r 30
Integrase strand Inhibitors
Raltegravir
Dolutegrav
ir
Elvitegravi
r/C
Entry Inhibitors
Maraviroc
Drug-Drug Interactions
No clinically relevant interaction
No data or risk of potential interaction
Concomitant use contraindicated or not recommended
![Page 18: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/18.jpg)
18
Conclusions
As highly effective treatments with few side effectsfor most HCV cases are now available:
• Most national guidelines demand prioritisation for higherfibrosis stages (Treat the sickest)
• HCV may be an eradicable disease (Treat all)
• In the future, treatment uptake will mainly be driven bythe cost debate (Treat who the payers are willing to pay)
![Page 19: Dr Patrick Ingiliz - BHIVA · 17/25 95/11287/114 85 PHOTON-26 HCV/HIV GT 3 SOF + RBV 24 weeks 85 94* 0 20 40 80 100 VALENCE 5 HCV PHOTON-14 HCV/HIV 212/250 16/17 PHOTON-26 HCV/HIV](https://reader033.vdocument.in/reader033/viewer/2022053119/60a0e30e052e586fa615fb6a/html5/thumbnails/19.jpg)
19
Acknowledgements:
Sanjay Baghani
Christoph Boesecke
in partnership
with