M-Puoti

Massimo Puoti
Dept. of Infectious Diseases
AO Ospedale Niguarda Cà Granda
Milan, Italy
Gestire i DAA
nella terapia della
coinfezione HCV HIV
Disclosures
• Grant/Research Support: BMS, Gilead Sciences,
MSD, Novartis, Pfizer, Roche, ViiV,
• Speaker’s Bureau: Abbvie, Beckman Coulter, BMS,
Gilead Sciences, Janssen, MSD, Roche, Roche
diagnostics, ViiV.
• Consultant in Temporary Advisory Board: Abbvie,
BMS, Gilead Sciences, Janssen, MSD, ViiV.
• Major shareholders no disclosures
• Other: no disclosures
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Raccomandazioni
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Raccomandazioni
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Indications in HIVCoinfected Patients
• Indications for HCV treatment in HCV/HIV coinfected persons are identical to those in patients
with HCV mono-infection
• Potential drug-drug interactions with
antiretroviral drugs should be taken into account
What to start: registration studies on IFN free
anti HCV drugs in PLHIV
Registration phase II/IIItrials of IFN free anti HCV treatments in Persons Living
with HIV (PLHIV): Screening failure % and Antiretrovirals allowed and not allowed
Study name
PHOTON I 1&
PHOTON II2
ION-43
ALLY – 24
Turquoise II5
C-EDGE
COINFECTION6
Anti HCV Drugs
SOFO + RBV
SOFO + LEDI
SOFO +
DACLA
Abbvie 3D
Grazoprevir
Elbasvir
Screening
failures n/tot %
(95% CI)
177/676
26%
(23-29%)
94/429
22%
(18-26%)
35/238
14%
(10-18 %)
50/113
44%
( 35-54%)
43/261
16%
(11-20%)
ABC
XTC
TDF
EFV
RIL
DAR/r
*
ATZ/r
LPV/r
FAMP/R
RAL
DOLU
1 Sulkowsky et al JAMA 2014; 312:353-61. 2 Molina JM Lancet 2015; 385: 1098-1106. 3 Naggie S N Engl J Med. 2015 Aug 20;373(8):705-13
4. Wyles DL N Engl J Med. 2015 ;373:714-25; 5. Sulkowsky MS et al JAMA. 2015;313:1223-1231.; 6 Rockstroh JK EASL Lncet HIV 2015;
Controlled studies on efficacy of IFN-free anti HCV
treatments in HIV/HCV co-infected patients
Modified from Rizzardini G, Fagiuoli S and Puoti M AIDS in press
Ruane P et al EACS 2015
Ruane P et al EACS 2015
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Raccomandazioni
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Real life data on Sofosbuvir + Simeprevir ( + RBV) in
HIV/HCV : CROI 2015
Author/ Pts
Character.
Abstract N SVR/ total
Grant J all
Marks K (PI exp)
Gilmore (cirrhotics)
649
644
647
18/20 (90%)
12/13 (92%)
22/29 (76%)
Del Bello D ( all)
All
645
26/29 (90%)
78/91 (86%)
DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN
IN PATIENTS WITH HIV-HCV COINFECTION: INTERIM ANALYSIS OF
A FRENCH MULTICENTER COMPASSIONATE USE PROGRAM
Fontaine H EASl 2015
Ingiliz P et al. EACS 2015
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Raccomandazioni
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Guidelines
• A guideline is a statement by which to determine a
course of action. A guideline aims to streamline
particular processes according to a set routine or
sound practice. ( U.S. Dept. of Veterans Affairs)
• Guidelines may be issued by and used by any
organization (governmental or private) to make the
actions of its employees or divisions more
predictable, and presumably of higher quality
MAP
Recommendations
• Something (as a course of action) that is
recommended as advisable to provide
healthcare professionals with timely guidance
• Sentences of practical import, oriented to
effecting an action
• Recommendations imply "ought-to" types of
statements and assertions, in distinction to
sentences that provide "is" types of statements
and assertions.
SVR12 after treatment with PR + TVR, SMV, FDV and
SOF in HCV G1 treatment-naïve patients: HIV + vs HIV –
SVR12 (%)
HIV +
HIV –
IN THE DAA ERA HIV+ WILL NOT BE A SPECIAL POPULATION
WITH AN UNMET NEED
Cirrhosis
28/38 285/363
42/53 419/521
169/239 414/570
21/23 296/327
87/114 104/159
24 or 48 weeks
24 or 48 weeks
12 or 24 weeks
12 weeks
24 weeks
10%
13%
11%
Excluded
Sulkowski M, AASLD 2012; TVR EU SmPC; Dieterich CROI 2014; Rockstroh J et al
EACS 2013 & AASLD 2013;
Rodriguez Torres M et al IDSA 2013; Naggie CROI 2014; SOF EU SmPC
Efficacy of Sofosbuvir + Ribavirin in HCV G2 (12 weeks) G1 G3 & 4 (24
weeks) stratified according to cirrhosis previous treatment and HIV
reactivity
% SVR12
SVR
104
181
4
14
301
67
98
52
112
58
85
49
27
2
3
28*
26
N
159
226
11
22
329
75
105
57
145
66
100
54
45
2
9
29*
31
Sovaldi SPC ; Sulkowsky et al. Ann Int Med 2014; Molina JM et al The Lancet 2015
Simeprevir and Sofosbuvir with modified doses of Ribavirin on
Telaprevir experienced HIV coinfected cirrhotics with HCV
A randomized open label pilot study: STOP C
Basu PP AASLD 2014
Sofosbuvir + Simeprevir in HIV/HCV vs HCV
Del Bello et al CROI 2015 abstract #45
Indications in HIVCoinfected Patients
• Indications for HCV treatment in HCV/HIV coinfected persons are identical to those in patients
with HCV mono-infection
• Potential drug-drug interactions with
antiretroviral drugs should be taken into account
Grazopevir + ELBASVIR : HIV+ vs HIV-
Nelson M et al IDSA 2015
LEDIPASVIR + SOFOSBUVIR 12 W
HIV + vs HIV -
Naggie S et al IDSA 2015
Management of Persons with Chronic
HCV/HIV Co-infection
* Fibro- Scan®: F0-F1 < 7.1 KPa; F2 7-10 KPa; F3/F4 > 10 Kpa
** Treatment must be considered independently from liver fibrosis in persons
with low CD4 count (<200 cells/µL), ongoing HIV replication, HBV coinfection, debilitating fatigue, extrahepatic manifestations, high risk of HCV
transmission (IVDU, prisoners, MSM with high risk behavior, fertile women who
want to be pregnant).
Impatto economico trattamento HCV+ con
Fibrosi F2 e Coinfezione da HIV e/o HBV
Lo Re V et al Ann Intern Med. 2014;160:369-79 Berenguer J, et al J Acquir Immune Defic Syndr.
2014 Jul 1;66(3):280-7 Macías J et al. Hepatology. 2015 May;61(5):1503-11. Donato F et al. Int J
Cancer. 1998 Jan 30;75(3):347-54. Cho LY, Int J Cancer. 2011 Jan 1;128(1):176-84. Papatheodoridis
GV et al J Hepatol. 2015;62:956-67. Morgan RL, et al Ann Intern Med. 2015;158:329-37.
Impatto del trattamento HCV+ F2 di altre categorie
con priorità nelle linee guida internazionali
Kondili et al AASLD 2015; Westbrook RH, J Hepatol. 2014;61:S58-68. Thein HH, Hepatology. 2008 Aug;48(2):41831. Morgan RL, Ann Intern Med. 2013;158:329-37. Hsu YC, Hepatology. 2014;59:1293-302. Monto A, Hepatology.
2002;36:729-36 Niederau C, Hepatology. 1998;28:1687-95.
HCV treatment options in HIV+
RBV =ribavirin SOF =sofosbuvir SMP =simeprevir DCV =daclatasvir LDV =ledipasvir OBV =ombitasvir PTV/r = paritaprevir/RTV DSV
=dasabuvir
I Cirrhotic persons with negative predictors of response can be treated 24 weeks with RBV (negative predictors: treatmentexperienced, platelet count < 75x103/uL)
II Possible extension up to 16 weeks in treatment-naïve cirrhotics or relapsers; up to 20 weeks in treatment-experienced cirrhotics
III Based on expert opinion and preliminary data from studies in persons on pre-marketing expanded access programmes
Algorithm for Management of Acute HCV in
Persons with Chronic HCV/HIV Co-infection
SVR 4 %
SOF + RBV treatment of acute hepatitis C in HIV+
3/11
11/12 10/17
Martinello et al. Abstract 1083 AASLD 2015;
Fierer et a.l Abstract 1090 AASLD 2015;
Naggie et al. Abstract 1094 AASLD 2015
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Raccomandazioni
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Characteritics that Inform anti HCV
Treatment Option Selection in HIV patients
Local
reimbursement
policy
Other drugdrug
interactions
Concurrent
cART and
possibility to
switch
Prior
treatment
experience
Treatment
selection
Patient comorbidities
HCV
genotype/
subtype
Severity
of liver
disease
Prevalence and Impact of Baseline NSA Resistance Associated
Variants (RAVs) on the Efficacy of Elbasvir / Grazoprevir
(EBR/GZR) Against GT1a Infection
Jacobson IM et al AASLD 2015
Characteristics that Inform anti HCV
Treatment Option Selection in HIV patients
Baseline
NS5 RAVs
in
selected
pts.
Other drugdrug
interactions
Concurrent
cART and
possibility to
switch
Local
reimbursement
policy
Treatment
selection
Prior
treatment
experience
HCV
genotyp
e/subtyp
e
Severity
of liver
disease
Patient comorbidities
Gestire i DAA
nella terapia della coinfezione HCV HIV
•
•
•
•
Studi Registrativi
Dati “Real Life”
Linee guida
Come iniziare ? Su quali caratteristiche scegliere
l’opzione di trattamento anti HCV nelle persone
con infezione da HIV
• Follow up in corso di terapia
Treatment Monitoring (IFN-Free)
Treatment
Treatment
Adherence
Baseline
0
RVR
2
4
SVR12
or EOT
EOT
6
12
18
Weeks
24
SVR12
or SVR24
30
36
Drug Induced Liver Injury (DILI) in anti HCV Therapy
• 26 cases reported of DILI in patients with CTP B cirrhosis treated
with Paritaprevir/r + Ombitasvir + Dasabuvir + RBV1
• Suspected DILI in 11/295 CTP B or C Cirrhosis treated in SOLAR-1
& SOLAR-2 with Sofosbuvir/Ledipasvir FDC  safety signal Direct
Bilirubin increase > 1 mg/dL 2
• ALT increase free DILI- Monitoring of hepatocellular function
in CTP B cirrhosis
• INR, Reflex Direct Bilirubin, Albumin every 2-4 weeeks especially during
the first 4 weeks
1 http://www.fda.gov/Drugs/DrugSafety/ucm468634.htm
2 Muir AJ et al AASLD 2015 Abstract # 96