Medical Director Specialty Services Southwest CARE Center Santa Fe New Mexico StateoftheART in Antiretroviral Management FORMATTED MMDDYY New Orleans Louisiana December 1517 2015 ID: 814861
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Slide1
Joel E. Gallant, MD, MPHMedical Director, Specialty ServicesSouthwest CARE CenterSanta Fe, New Mexico
State-of-the-ART in Antiretroviral Management
FORMATTED: MM/DD/YY
New Orleans, Louisiana: December 15-17, 2015
Slide2START: 57% Reduced Risk of Serious Events or Death With Immediate ART1.8% vs 4.1% in deferred vs immediate arms experienced serious AIDS or non-AIDS related event or death: HR = 0.43 (95% CI: 0.30 to 0.62);
P < .001
10
8
6
4
2
0
Cumulative Percent With Event
0
6
12
18
24
30
36
42
48
54
60
Month
Deferred ART
Immediate ART
Lundgren J, et al.
N
Engl
J Med.
2015
Slide 6 of 38
Slide3GS104/111: Smaller decline in hip and spine BMD with TAF
Smaller decline in hip and spine BMD with TAF
0
24
48
0
24
48
0
-6
-4
-2
0
2
Wk
Wk
0
-6
-4
-2
0
2
=845
=850
797
816
784
773
836
848
789
815
780
767
-1.30
-2.86
-0.66
-2.95
P
< .001
P
< .001
Mean % Change From BL
Sax P, et al. CROI 2015. Abstract 143.
n
n
TAF/FTC/EVG/COBI (n = 866)
TDF/FTC/EVG/COBI (n = 867)
Slide 17 of 38
Slide4GS 104/111: TAF vs. TDF: Quantitative Proteinuria
Median % Change from Baseline (Q1, Q3)
Protein
(UPCR)
Albumin (UACR)
RBP
Beta2- microglobulin
p <0.001
for all
Urine [protein]:Creatinine Ratio
76
133
168
E/C/F/TAF
E/C/F/TDF
Baseline
44mg/g44mg/g5mg/g5mg/g
64μg/g 67μg/g 101μg/g
103μg/g Sax P, et al. 22nd CROI; Seattle, WA; February 23-26, 2015. Abst. 143LB.
Protein (UPCR)Albumin (UACR)RBP
Slide 19 of 38
Slide5GS-109: Switch
from TDF-based Regimens to
E/C/F/TAF: Renal and Bone Outcomes
Hip BMD was similarly increased for pts treated with TAF regimen
Mills A, et al. IAS 2015. Abstract TUAB0102.
Regimen
Renal Events Leading to Discontinuation
EVG/COBI/
FTC/TAF
(n = 959)
Acute renal failure
Interstitial nephritis
TDF-Based Regimen
(n = 477)
Chronic kidney disease
Elevated serum creatinine
Fanconi syndrome (mild jaundice)Increased creatinineNephretic colic (nephrolithiasis)
4
3
2
1
0
-1
-2
-3
Median % Change
in BMD (Q1, Q3)
Baseline
Week 24
EVG/COBI/FTC/TAF
TDF-Based Regimen
Week 48
1.79
-0.28
P
< .001
Slide 23 of 38
Slide6GS-112: Switching to E/C/F/TAF Regimen With Renal Impairment (
eGFR
30-60)
Changes in
eGFR
to
Wk
48
Changes in spinal BMD
to
Wk
48
Gupta S, et al. IAS 2015. Abstract TUAB0103.
Total
TDF
Non-TDF
Median Change from Baseline
10
0
-10
-0.6
+0.2
-1.8
-1.8*
-1.5
-2.7*
Baseline:
56
58
53
54
56
50
eGFR
CG
mL/min
eGFR
CKD
-EPI Cr
mL/min/1.73m
2
*
P
< 0.05.
Total
TDF
Non-TDF
*P <
0.05.
4
2
0
-2
Mean % Change
Spine BMD
2.95*
2.29*
0.99
Multicenter, open-label phase III trial, N=242 (158 on TDF, 84 on non-TDF-based regimen)
Slide 24 of 38
Slide7GS 119: Virologic Suppression After Switch to EVG/COBI/FTC/TAF + DRV
Similar rates of maintained virologic suppression at Wk 24, but significantly higher rates with switch vs baseline ART at Wk
48
Huhn
S, et al. ID Week 2015. Abstract 726.
Week 24
VL< 50
Virologic Failure
No Data
EVG/COBI/FTC/TAF +
DRV
Baseline ART
100
80
60
40
20
0
Patients (%)
97
91
2
0
1
9
Week 48
VL < 50
Virologic Failure
No Data
94
76
2
11
3
13
Treatment difference: 5.3%
(95% CI: -3.4 to 17.4;
P
= .23)
Treatment difference: 18.3% (95% CI: 3.5 to 33;
P
= .004)
Slide 26 of 38
Slide85
2
STRIIVING: Virologic Outcomes at
Wk
24
Switch to DTG/ABC/3TC
noninferior
to maintaining baseline ART
No cases of protocol-defined virologic failure
3 pts in DTG/ABC/3TC arm (1%) and 4 pts in BL ART arm (1%) had
VL > 50 but < 100 through
Wk
24
Trottier
B, et al.
ICAAC 2015.
Primary Efficacy Analysis: ITT-Exposed and Per Protocol Populations
100
80
60
40
20
0
Virologic
Success
Virologic
Nonresponse
No Virologic Data
HIV-1 RNA < 50 c/mL (%)
DTG/ABC/3TC (ITT-E, n = 274)
Baseline ART (ITT-E, n = 277)
DTG/ABC/3TC (PP, n = 220)
Baseline ART (PP, n = 215)
85
88
93
93
14
10
6
1
1
< 1
12
-12
-8
-4
0
4
8
12
-12
-8
-4
0
4
8
-4.9
-0.3
4.4
2.3
-9.1
ITT-E Population
PP Population
-3.4
DTG/ABC/3TC
Baseline ART
Slide 29 of 38
Slide9PADDLE: All Pts Virologically Suppressed by Wk 8 of DTG + 3TC
Included 4 pts with VL > 100,000 at BL
Figueroa MI, et al. EACS 2015. Abstract 1066.
Pt #
HIV-1 RNA (copies/
mL
)
Screen
BL
Day 2
Day 4
Day 7
Day 10
Wk
2
Wk
3
Wk 4Wk 6Wk 8
Wk
12
Wk
24
1
5584
10,909
3701
383
101
71
< 50
< 50
< 50
< 50
< 50< 50< 50
2888710,2335671
318< 50< 50< 50
< 50< 50< 50< 50
< 50< 50367,335
151,56937,6041565
11782669753< 50
< 50< 50< 50
< 50499,291148,370
11,7973303432179
17855< 50< 50
< 50< 50< 505
34,36220,54446801292570168107< 50< 50< 50< 50< 50
< 50616,02414,49937541634162< 50< 50< 50
< 50< 50< 50< 50
< 50
7
37,604
18,597
2948
819
61
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
8
25,071
24,368
6264
1377
Not
done
268
105
< 50
< 50
< 50
< 50
< 50
< 50
9
14,707
10,832
Not
done
516
202
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
10
10,679
7978
5671
318
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
11
50,089
273,676
160,974
68,129
3880
2247
784
290
288
147
< 50
< 50
< 50
12
13,508
64,103
3496
3296
135
351
351
84
67
< 50
< 50
< 50
< 50
13
28,093
33,829
37,350
26,343
539
268
61
< 50
< 50
< 50
< 50
< 50
< 50
14
15,348
15,151
3994
791
198
98
< 50
61
64
< 50
< 50
< 50
< 50
15
23,185
23,500
15,830
4217
192
69
< 50
< 50
< 50
Not
done
< 50
< 50
< 50
16
11,377
3910
370
97
143
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
17
39,100
25,828
11,879
1970
460
147
52
< 50
< 50
< 50
< 50
< 50
< 50
18
60,771
73,069
31,170
2174
692
358
156
< 50
< 50
< 50
< 50
< 50
< 50
19
82,803
106,320
35,517
2902
897
352
168
76
< 50
< 50
< 50
< 50
< 50
20
5190
7368
3433
147
56
< 50
< 50
< 50
< 50
< 50
< 50
< 50
< 50
Slide 32 of 38
Slide10LATTE: Virologic Success Through Maintenance Week 966 pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48
Margolis D, et al. CROI 2015. Abstract 554LB.
VL < 50 c/mL by Snapshot Algorithm (%)
100
80
60
40
20
0
BL
4
12
24
28
36
48
72
96
Induction Phase
Maintenance Phase
CAB 10 mg (n = 60)
CAB 30 mg (n = 60)*
CAB 60 mg (n = 61)
EFV 600 mg (n = 62)
68%
63%
84%
75%
Wks
*
Cabotegravir
30 mg selected for future development
Slide 33 of 38
Slide11Recent Switch Studies: Suppressed Patients
Trial
From
To
Outcome
GS-123
TDF/FTC + RAL
EVG/COBI/FTC/TDF
✔
GS-264
TDF/FTC/EFV
RPV/FTC/TDF
✔
Strategy
-NNRTI
TDF/FTC + NNRTIEVG/COBI/FTC/TDF
✔Strategy-PITDF/FTC + PI/rEVG/COBI/FTC/TDF
✔SPIRIT2 NRTI + PI/r
RPV/FTC/TDF✔SPIRAL2 NRTI + PI/r (exp’d pts)
2 NRTI + RAL✔SALTATV/r + 2 NRTI
ATV/r + 3TC
✔
OLE
LPV/r + 2 NRTIs
LPV/r + 3TC
✔
GS-109
TDF-based ART
EVG/COBI/FTC/TAF
✔
STRIIVING
Suppressive ART
DTG/ABC/3TC
✔
ATLAS-M
ATV/r + 2 NRTIsATV/r + 3TC
✔GS-119“Salvage regimen” (exp’d pts)
EVG/COBI/FTC/TAF + DRV✔LATTECAB or EFV + 2 NRTIs
CAB + RPV✔SWITHCMRK 2 NRTI + LPV/r (
exp’d pts)2 NRTI + RAL✗MARCH
2 NRTI + PI/rPI/r + MVC✗HARNESS
2 NRTI + 3rd AgentATV/r + RAL✗
Adapted from David Wohl
Slide 34 of 38