Download Castagna A. et al, SIMIT 2016

LONG-TERM EFFICACY OF DOLUTEGRAVIR (50 MG BID)
INCLUDING REGIMENS IN INI-RESISTANT FAILING HIV-1
INFECTED SUBJECTS IN ITALY:
DATA FROM THE PRESTIGIO NATIONAL DATABASE
Antonella Castagna 1,2, Laura Galli1, Micol Ferrara3, Mauro Zaccarelli4, Antonio Di Biagio5,
Marianna Menozzi6, Annachiara Cericola7, Eleonora Magistrelli8, Antonio Muscatello9, Andrea
Roncadori10, Giuseppe Forastieri11, Paolo Rizzini11 on behalf of the PRESTIGIO National
Database*
1- Infectious Diseases Department, San Raffaele Scientific Institute, Milan; 2- Vita Salute San Raffele University, Milan; 3- Dipartimento Scienze
Mediche, Unità di Malattie Infettive, Università di Torino ; 4- Istituto Nazionale per le Malattie Infettive, Lazzaro Spallanzani, IRCCS, Roma; 5Infectious Diseases Unit, IRCCS AOU San Martino-IST, Genova; 6- Clinic of Infectious Diseases, University of Modena, Modena; 7- SC Farmacia
Ospedaliera, EO Ospedali Galliera, Genova; 8- Infectious Diseases Clinic, Policlinico Sant’Orsola Malpighi, Università degli studi di Bologna, Bologna;
9- Infectious Diseases Clinic, San Gerardo Hospital, University of Milano-Bicocca, Monza10 - Healthcare Sytems Department, CINECA, Casalecchio di
Reno, Bologna; 11- ViiV Healthcare, Verona
Financial Disclosures
Antonella Castagna has received consulting fees, fees for non CME
services and travel grants from Abbott, Bristol-Myers Squibb, Gilead
Sciences, MSD, Janssen, MSD and ViiV Healthcare
Castagna A. et al, SIMIT 2016
Background
Among 3012 US patients udergoing integrase GRT for clinical decision making
471 patients had viruses with ≥ 1 raltegravir or elvitegravir resistance
mutation (15.6%)1
In 2015 prevalence of Integrase drug resistance Mutations in ART-Treated
Persons in BC is 6.8% 2
Dolutegravir (DTG) 50 mg twice daily has been proven to be effective as
rescue therapy in treatment-experienced patients with INI resistance.
In VIKING-3 69% of subjects achieved <50 c/mL at week 243
In VIKING-4 47% and 57% of subjects had HIV-1 RNA <50 and <400 copies/ml
at week 24, and 40% and 53% at week 48, respectively4
No long-term efficacy data are available.
1- Hurt CB, CID 2014; 2- Lepik KJ, CROI 2016; 3- Castagna A, JID 2014; 4- Akill B, Antivir Ther 2015
Castagna A. et al, SIMIT 2016
PRESTIGIO
PRESTIGIO (Studio Osservazionale Pazienti Resistenti agli INSTI: Sistema di
Monitoraggio) is a national Information System enabling a standardized
management of the diagnostic-therapeutic process and a real-time monitoring
of TIVICAY use in HIV-infected patients resistant to integrase inhibitors in many
italian centers for the HIV-infection treatment.
The CINECA application platform allows :
A real-time monitoring of TIVICAY use
Information collection directly from the source (clinical/pharmacy units), in
a standardized form and with a central control
34 Italian centers actively involved since November 2014
Castagna A. et al, SIMIT 2016
Aim of the study
To evaluate long- term efficacy of dolutegravir 50 mg
BID- including regimens in Italian HIV-1 infected INIresistant failing subjects
Castagna A. et al, SIMIT 2016
Methods
Treatment-experienced HIV-1 infected patients:
• with integrase inhibitor (INI)-resistant virus,
• receiving DTG 50 mg twice daily in association with an
optimized background therapy (OBT)
• recorded in the PRESTIGIO database with demographic,
clinical, virological and immunological data associated with
DTG 50 mg BID prescription in Italy
were used for this analysis.
Pts’ follow-up accrued from the start of DTG 50mg+OBT until DTG
discontinuation or last visit.
Virological efficacy was defined by a viral load [VL] <50 cps/mL at
last observed visit.
Castagna A. et al, SIMIT 2016
Start of PRESTIGIO
Patient included
Start of DTG
Patient not included
Interruption of DTG
Start of DTG
Patient included
Start of DTG
Start of DTG
Patient included
Interruption
of DTG
Patient included
Start of DTG
01/11/2014
Interruption of DTG
time
Castagna A. et al, SIMIT 2016
PRESTIGIO: patients disposition (July 2016)
Patients recorded in the PRESTIGIO database
N=177
Patients with available information
N=162
Patients with
HIV-RNA<50 copies/mL at DTG start
Patients with
HIV-RNA >50 copies/mL at DTG start
N=27
n=135
Patients with ≥1 follow-up visit
[median (IQR): 3 (1-5)]
n=112
Castagna A. et al, SIMIT 2016
PRESTIGIO: Baseline characteristics
Characteristics
N=135
Age (years)
Male gender
Italian nationality
51.4 (47.0-55.0)
95 (70%)
126 (93%)
HCV infection
41 ( 34%)
Years since HIV-1 infection
22.0 (17.0-27.0)
With resistance mutations to raltegravir/ elvitegravir
133 (99%)
Previous inclusion in the Viking o EAP
44 (33%)
Baseline DTG calendar year <2014
2015
2016
Baseline HIV-RNA (copies/mL)
>100000
Baseline CD4+ (cells/µL)
≤200
Median (IQR) or frequency (%)
49 (36%)
73 (54%)
13 (10%)
6500 (586-44553)
27 (20%)
280 (149-518)
49 (36%)
Castagna A. et al, SIMIT 2016
PRESTIGIO: Optimized Background therapy
Optimized Background therapy
N=135
OBT > 3 drugs (including DTG)
50 (37%)
PI-sparing regimens
NNRTI-sparing regimens
NRTI-sparing regimens
24 (18%)
97 (72%)
66 (49%)
NRTI most frequently used
TDF
FTC
3TC
43 (32%)
35 (26%)
22 (16%)
ETV
RPV
27 (20%)
11 (8%)
DRV
ATV
LPV
93 (69%)
10 (7%)
7 (5%)
NNRTI most frequently used
PI/r most frequently used
Enfuvirtide use
7 (5%)
Maraviroc use
35 (26%)
Castagna A. et al, SIMIT 2016
PRESTIGIO : DTG 50 mg BID discontinuation
14/112 (12.5%)
Castagna A. et al, SIMIT 2016
PRESTIGIO: Virological Efficacy
100
Number
of pts
80
67%
60
40
20
0
BL
135
12
64
24
36
48
16
12
8
DTG exposure (months)
% of patients (95%CI) with
HIV-RNA <50copies/mL
% of patients (95%CI) with
HIV-RNA <50copies/mL
100
baseline CD4+ >200 cells/L
80
71%
60
60%
40
20
0
BL
>48
12
baseline CD4+ 200 cells/L
12
n=21
n=43
24
n=7
n=9
36
n=6
n=6
48
n=4
n=4
>48
n=5
n=7
DTG exposure (months)
PI-sparing regimen
PI-including regimen
80
70%
60
50%
40
20
0
BL
baseline VL100000 copies/mL
baseline VL>100000 copies/mL
100
12
n=15
n=49
24
n=3
n=13
36
48
n=2
n=0
n=10
n=8
DTG exposure (months)
>48
n=2
n=10
% of patients (95%CI) with
HIV-RNA <50copies/mL
% of patients (95%CI) with
HIV-RNA <50copies/mL
100
80
75%
60
50%
40
20
0
BL
12
n=56
n=8
24
36
48
>48
n=12
n=8
n=7
n=4
n=4
n=1
DTG exposure (months)
n=8
n=4
Castagna A. et al, SIMIT 2016
PRESTIGIO : DTG Resistance associated mutations
ID
BL
HIV-RNA
(cps/mL)
LAST
HIV-RNA
(cps/mL)
BL CD4+
(cells/µL)
LAST
CD4+
(cells/µL)
DTG
exposure
(months)
Viral
tropism
RAM at DTG start
RAM at last visit while
on DTG
BL ART REGIMEN
31
2118674
1045164
19
4
54
D/M
None
G140S,Q148H,E138K,
T97A
DTG, DRV/r, ETV,
3TC
73
3700
99096
34
7
41
D/M
G140S,Q148H,
E138A,Y143H
G140S,Q148H,Y143H,
E138A, T97A
DTG, DRV/r, 3TC
78
134924
594419
39
12
77
R5
Y143CHR
G140S,Q148H,Y143R,
E138K, L74M,T97A
DTG, FTC, TDF
25
18290
3257
191
172
26
NA
G140S,Q148H,E138A
G140S,Q148H,T97A
DTG, ETV, FTC, TDF
65
3997
8845
323
375
25
X4
None
Q148R,N155H,S147G,
E138K, H51Y, T97A
DTG, DRV/r
167
1224
7441
594
434
10
NA
G140S,Q148H,T97A
G140N/S,Q148H,
E138K
DTG, LPV/r, FTC,
TDF
24
18621
1453
530
626
67
X4
G140S,Q148H,
E138K,T97A
DTG, DRV/r, ETV,
FTC, TDF
188
519
3777
345
427
26
NA
G140S, T97A
G140S,Q148H,
E138K, T97A,N165I
DTG, LPV/r, TDF
16
147000
36830
131
43
36
X4
G140S,Q148H
G140S,Q148H,T97A
DTG, DRV/r, ETV,
FTC, TDF
G140S,Q148H,M154I
Castagna A. et al, SIMIT 2016
PRESTIGIO: CD4 Recovery
CD4+ change
from baseline (cells/uL)
Baseline CD4+ (cells/uL)
1500
1200
900
600
300
307
267
251
238
199
600
baseline CD4+ 200 cells/L
500
baseline CD4+ >200 cells/L
400
+376
+313
300
+260
200
+147
+63
100
+121
+106
+95
+96
+22
0
-100
0
12
12-24
24-36
36-48
-200
BL
>48
12
24
n=21
n=43
DTG exposure (months)
n=7
n=9
36
n=6
n=6
48
n=4
n=4
>48
n=5
n=7
Months of Follow-Up
1200
PI-sparing regimen
1000
+528
500
400
+365
300
+272
200
+118
100
+36
0
-100
BL
12
n=15
n=49
+138
+143
+121
+32
CD4+ change
from baseline (cells/uL)
CD4+ change
from baseline (cells/uL)
PI-based regimen
500
baseline VL100000 copies/mL
baseline VL>100000 copies/mL
400
+339
+300
300
n=3
n=13
36
n=2
n=10
Months of Follow-Up
48
>48
n=0
n=8
n=2
n=10
+263
200
+98
100
-100
BL
+149
+138
+107
+63
+28
0
24
+912
12
n=56
n=8
24
36
48
>48
n=12
n=4
n=8
n=4
n=7
n=1
n=8
n=4
Months of Follow-Up
Castagna A. et al, SIMIT 2016
Conclusions
In INI-resistant HIV-1 infected subjects, treated With DTG 50 mg BID
including regimens, consistent efficacy data even in a long-term
observation were observed.
Need to share strategies in order to properly:
maintain virological success in virologically suppressed
manage subjects with low-level viremia
manage failing subjects according with CD4 level and residual
therapeutic options
Castagna A. et al, SIMIT 2016
GRAZIE
PRESTIGIO PARTICIPATING SITES
Ancona: L. Butini, A. Costantini, A. Giacometti, M. Tavio; Asti: M. Grassini, M. Valle; Aviano: E. Vaccher, F. Martellotta, O.
Schioppa; Bergamo: L. Comi, F. Maggiolo; Bologna: P. Viale, M. Borderi, L. Calza, L. Moratello, E. Magistrelli; Brescia, F.
Castelli, E. Festa, E. Focà; Busto Arsizio: T. Quirino; Cagliari: M. Campus, F. Businco; Cremona: A. Pan, C. Fornabaio;
Firenze: F. Mazzotta, M. Di Pietro, C. Sterrantino, A. Bartoloni; Foggia: S. Ferrara; Forlì-Cesena: C. Cancellieri, S. Di
Cesare; Genova: C. Viscoli, A. Di Biagio, G. Cassola, G. Cenderello, G. Penco, A Cericola; Grosseto: C. Nencioni, T. Carli;
Legnano: P. Viganò, T. Re; Lucca: A. Del Fiorentino; Mantova: G. Gattuso, L. Palvarini, M.Taurozzi; Milano: A. Lazzarin, A.
Carbone, A. Castagna, S. Rusconi, S. E. Salvaggio M. Galli; Modena: C. Mussini, M. Menozzi. Monza: A. Gori, A.
Muscatello, E. Cappelletti; Novara: PL Garavelli, O. Bargiacchi; Palermo: T. Prestileo, F. Di Lorenzo, Silvana Bonanno;
Parma: C. Ferrari, AM. degli Antoni, Padova: AM. Cattelan; Pisa: F. Menichetti, R.Iapoce; Perugia: F. Baldelli, E. Schiaroli,
F. Italiani; Reggio Emilia: G. Magnani, R. Corsini, E. Barchi, E. Ferrari; Roma: A. Antinori, M. Zaccarelli, A. Cristaudo, A.
Latini, R. Cauda, V. Vullo, G. Maffongelli, M. Andreoni; Rovigo: L. Sassett, F. Viviani; Siracusa: A. Franco; Taranto: F. Resta;
Torino: G. Di Perri, S. Bonora, M. Ferrara; Udine: M. Bassetti, A. Londero; Verona: M. Malena.
CINECA
ViiV-Healthcare
Investigator Meeting Progetto PRESTIGIO: 11 novembre 2016,
Hotel Michelangelo, Sala Laurenziana, Milano
Vi aspettiamo !
Castagna A. et al, SIMIT 2016