Durability of Dolutegravir (50 mg BID) including

Durability 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; 5‐
Infectious 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
OC 78
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, ICAR 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‐ Eron JJ, CID 2014; 2‐ Lepik, CROI 2016; 3‐ Castagna JID 2014; 4‐ Akil, Antivir Ther, 2014
Castagna A. et al, ICAR 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
Up to date 34 Italian centers actively involved since November 2014
Castagna A. et al, ICAR 2016
Aim of the study
To evaluate long‐ term efficacy of dolutegravir 50 mg BID‐ including regimens in Italian HIV‐1 infected INI‐
resistant failing subjects
Castagna A. et al, ICAR 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.
Castagna A. et al, ICAR 2016
PRESTIGIO: patients disposition (may 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, ICAR 2016
PRESTIGIO: Baseline characteristics
Characteristics
Age (years)
Male gender
Italian nationality
51.4 (47.0‐55.0)
95 (70%)
126 (93%)
HCV infection Years since HIV‐1 infection
With resistance mutations to raltegravir/ elvitegravir
Previous inclusion in the Viking o EAP Baseline DTG calendar year <2014
2015
2016
Baseline HIV‐RNA (copies/mL)
Baseline CD4+ (cells/µL)
Median (IQR) or frequency (%)
N=135
41 ( 34%)
22.0 (17.0‐27.0)
133 (99%)
44 (33%)
49 (36%)
73 (54%)
13 (10%)
6500 (586‐44553)
280 (149‐518)
Castagna A. et al, ICAR 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, ICAR 2016
PRESTIGIO : DTG 50 mg BID discontinuation
14/112 (12.5%) Castagna A. et al, ICAR 2016
PRESTIGIO: Virological Efficacy
LAST STUDY VISIT (LSV)
HIV‐RNA at LSV<200 cps/mL
HIV‐RNA at LSV 200 cps/mL
100
80
67%
60
80
% subjects
% of patients with
HIV‐RNA <50copies/mL
100
40
60
40
20
20
0
0
BL 12 24 36 48 >48
Number of pts 135 75 18 14 17 12
DTG exposure (months)
At LSV 75 pts with HIV‐RNA < 50 copies/ml
37 pts with HIV‐RNA > 50 copies/ml
16 pts with HIV‐RNA > 200 copies/ml
94%
75%
67%
88%
75%
12 12‐24 24‐36 36‐48 >48
64
16
12
12
DTG exposure (months)
8
Castagna A. et al, ICAR 2016
PRESTIGIO : Subjects with HIV‐RNA > 200 copies/ml at last visit
ID
BL
LAST
LAST DTG BL CD4+ HIV‐RNA HIV‐RNA CD4+
exposure (cells/µL)
(cps/mL) (cps/mL)
(cells/µL) (months)
ART REGIMEN
31
2118674
1045164
19
4
54
DTG, DRV/r, ETV, 3TC
73
3700
99096
34
7
41
DTG, DRV/r, 3TC
78
134924
594419
39
12
77
DTG, FTC, TDF
16
147000
36830
131
43
36
DTG, DRV/r, ETV, FTC, TDF
70
249102
380352
9
92
17
DTG, T20, MCV, TPV/r, FTC, TDF
105
44553
181194
224
119
10
DTG, T20, MVC
49
45257
22328
139
128
11
DTG, DRV/r, ETV
117
7771
23867
174
141
32
DTG, DRV/r, MCV FTC
115
414403
50435
38
152
9
DTG, DRV/r, ETV
25
18290
3257
191
172
26
DTG, ETV, FTC, TDF
65
3997
8845
323
375
25
DTG, DRV/r
167
1224
7441
594
434
10
DTG, LPV/r, FTC, TDF
143
146
613
534
494
15
DTG, DRV/r, FTC, TDF
158
1408
302
664
516
12
DTG, T20, DRV/r, ETV
62
2300000
503
198
526
14
DTG, DRV/r, MCV, TDF
24
18621
1453
530
626
67
DTG, DRV/r, ETV, FTC, TDF
Castagna A. et al, ICAR 2016
PRESTIGIO : DTG Resistance associated mutations
ID
BL
HIV‐RNA
(cps/mL)
LAST
BL CD4+ HIV‐RNA (cells/µL)
(cps/mL)
31
2118674
1045164
73
3700
78
LAST CD4+
(cells/µL)
DTG exposure
(months)
Viral
tropism
RAM at DTG start
RAM at last visit
while on DTG
ART REGIMEN
19
4
54
D/M
None
G140S,Q148H,E138K
T97A
DTG, DRV/r, ETV, 3TC
99096
34
7
41
D/M
NA
G140S,Q148H, E138A,Y143H,T97A
DTG, DRV/r, 3TC
134924
594419
39
12
77
R5
Y143CHR
G140S,Q148H,E138, Y143R,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
Q148H,E138K,S147,
N155H,T97A,H51Y
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,M154I
G140S,Q148H, E138K,T97A
DTG, DRV/r, ETV, FTC, TDF
143
146
613
534
494
15
X4
NA
G140S,Q148H,T66I,
T97A
DTG, DRV/r, FTC, TDF
Castagna A. et al, ICAR 2016
PRESTIGIO: CD4 Recovery
500
400
1200
900
600
300
0
307
267
199
238
251
12 12‐24 24‐36 36‐48 >48
DTG exposure (months)
CD4+ change
from baseline (cells/uL)
Baseline CD4+ (cells/uL)
1500
300
+263
+169
200
100
+118
+111
+41
0
‐100
‐200
BL
12
n=66
24
36
48
>48
n=13
n=11
n=9
n=11
DTG exposure (months)
Castagna A. et al, ICAR 2016
Conclusions
In INI‐resistant HIV‐1 infected failing 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
We invite you to participate to the Italian cohort of HTE subjects
Castagna A. et al, ICAR 2016
GRAZIE
PRESTIGIO PARTICIPATING SITES
Ancona: L. Butini, A. Costantini, A. Giacometti; Asti: M. Grassini; Bologna: P. Viale, M.
Borderi, L. Calza, L. Moratello; Brescia: F. Castelli; Cremona: A. Pan, C. Fornabaio;
Firenze: F. Mazzotta, M. Di Pietro; 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; Mantova: G. Gattuso, L.
Palvarini, M. Taurozzi; Milano: A. Lazzarin; A. Carbone, A. Castagna; Modena: C.
Mussini, M. Menozzi. Monza: A. Gori, A. Muscatello; Novara: PL Garavelli, O.
Bargiacchi; 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; Roma: A. Antinori, M. Zaccarelli, A. Cristaudo, A. Latini,
R. Cauda, V. Vullo; Rovigo: L. Sassett, F. Viviani; Taranto: F. Resta; Torino: G. Di Perri, S.
Bonora, M. Ferrara; Udine: M. Bassetti; Verona: M. Malena.
CINECA
ViiV‐Healthcare
Castagna A. et al, ICAR 2016