STRIIVING Study Design Endpoints Primary proportion of patients maintaining HIV RNA lt 50 cmL at W48 ITTE snapshot noninferiority if lower margin of the twosided 95 CI for the difference 10 90 power ID: 537597
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Slide1
Switch to DTG/ABC/3TC
STRIIVING
NEAT 022Slide2
Design
Endpoints
Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W24
(ITT-E, snapshot) ; non-inferiority if lower margin of the two-sided 95% CI for the difference = - 10%, 90% power Secondary: CD4 cell count changes, safety, lipid, renal, bone and cardiovascular changes, development of resistance, treatment satisfaction
Switch to DTG/ABC/3TC
Continue current ART
Randomisation *
1 : 1Open-label
HIV+ ≥ 18 yearsHIV RNA < 50 c/mL On 2 NRTI + PI/r or NNRTI or INSTI stable ≥ 6 monthsHLA-B*5701 negativeHBs Ag negative
N = 278
N = 275
W24
W48
STRIIVING
Study
: switch to DTG/ABC/3TC
Switch to DTG/ABC/3TC
STRIIVING
Trottier
B.
Antivir Ther. 2017;22(4):295-305.
* Randomisation
was
stratified
by 3rd agent (PI, INSTI or NNRTI)Slide3
STRIIVING Study: switch to DTG/ABC/3TC
DTG/ABC/3TC
N = 275
Continuation of current ART (deferred switch)
N = 278
Median age, years
45
47
Female, %
14
14
Hepatitis C
coinfection
, %
8
5
Median time on current ART, months
54
51
CD4 cell count (/mm
3
), median
618
597ART at randomisation, %PINNRTIINSTITDF/FTC backbone4332257642312779Discontinuation, NW0-W24 / W24-W48For adverse eventFor protocol deviationLost to follow-upFor other reasons36 / 910 / 015 / 03 / 58 / 433 / 140 / 417 / 13 / 313 / 6
Baseline characteristics and patient disposition
STRIIVING
Trottier
B.
Antivir
Ther
. 2017;22(4):295-305.Slide4
HIV RNA < 50 c/
mL
(
ITT-e)STRIIVING
* Analysis restricted to patients with deferred switch
85
1
14
88
1
10
83
< 1
1792 17
0
20
406080100%
DTG/ABC/3TC
Immediate
switch D1-W24 (N = 275)
Continuation
cART
D1-W24 (N = 278)
DTG/ABC/3TCImmediate switch D1-W48 (N = 275)DTG/ABC/3TCDeferred switch W24-W48 (N = 244 *) No subjects met protocol-defined virologic failure in either study arm ; 4 subjects with HIV RNA > 50 c/mL at W48 (1 early switch, 3 deferred switch) ; all 4 resuppressed < 50 c/mLVirologic successVirologic non responseNo virologic dataSTRIIVING Study: switch to DTG/ABC/3TCAt week 24- Lower bound for theadjusted difference : - 9.1 %(non-inferiority), by ITT-E- Success in 93 % in bothgroups in the per-protocolanalysis (difference : - 0.2;95% CI : - 5.0 to 4.6)Trottier B. Antivir Ther. 2017;22(4):295-305.Slide5
DTG/ABC/3TC
(N = 276)
Continuation of
cART
(N = 277)
Any adverse event
183 (66)
129 (47)
Drug-related
adverse event
59 (21)
4 (1)
Adverse event grade 3-4
8 (3)
5 (2)
Serious adverse event
6
(2)
5
(2)
Discontinuation for adverse event
11 (4)
0
Adverse event in ≥ 5% in either groupCough14 (5)8 (3)Diarrhea17 (6)4 (1)Fatigue19 (7)3 (1)Headache13 (5)4 (1)Nausea27 (10)3 (1)Upper respiratory tract infection
21 (8)
20 (7)
Psychiatric
35 (13)
8 (3)
Adverse events at W24, n (%)
111
STRIIVING
Trottier
B.
Antivir
Ther
. 2017;22(4):295-305.
STRIIVING
Study
: switch to DTG/ABC/3TCSlide6
Grade
Onset
Prior ARV
(3
rd
drug)
1
Insomnia
2
W1
LPV/r
2
Diarrhea, flatulence, rash,
Abdominal
pain
, anxiety,
nausea, body ache
1
2W1W1
RPV
3
Euphoric
mood
, Headache12W1ATV/r4Abdominal cramps, chills, diarrhea, dizziness, headache2W1RAL5Pruritus2W1NFV6Upper abdominal pain, diarrheaFatigue1, malaiseFlu-like syndrome DepressionProfuse sweating, change in body odor12121W1W1W9W12W17NVP7Nasal congestionWorsening fatigueNausea12
3
W2
EVG/c
8
Alopecia
1
W4
ATV/r
9
Fatigue
1
1
W8
DRV/r
10
Homicide
1
NA
W10
RAL
1
Not drug-related
Adverse events leading to discontinuation of DTG/ABC/3TC (N = 10)
112
STRIIVING
Study
: switch to DTG/ABC/3TC
STRIIVING
Trottier
B.
Antivir
Ther
. 2017;22(4):295-305.Slide7
Total
cholesterol
HDL -
cholesterol
LDL-
cholesterol
Triglycerides
Total cholesterol:
HDL ratio
DTG/ABC/3TC
ART
DTG/ABC/3TC
ART
DTG/ABC/3TC
ART
DTG/ABC/3TC
ART
DTG/ABC/3TC
ART
Change
from baseline
at
W
24 (SD)3.33 (31.88)-0.59 (25.05)-0.47 (8.77)-1.45 (8.43)4.47 (24.08)0.93 (21.95)0.17 (99.59)-5.74(76.93)0.14 (0.88)0.05 (0.78)Fasting Lipids, mean mg/dLSTRIIVING Study: switch to DTG/ABC/3TCSTRIIVINGDTG/ABC/3TC at W24Continuation ART at W24DTG/ABC/3TC at BaselineContinuation ART at Baseline3.52.51050.5
1.5
2
3
4
4.5
Total cholesterol:HDL ratio
140
100
40
0
200
20
60
80
120
160
180
Total cholesterol
HDL
LDL
Triglycerides
Trottier
B.
Antivir
Ther
. 2017;22(4):295-305.Slide8
Mean change from baseline in serum
creatinine
(mg/
dL
) through 24 weeksSTRIIVING Study: switch to DTG/ABC/3TCSTRIIVING
Trottier B. Antivir Ther. 2017;22(4):295-305.
Small, non-progressive changes in serum creatinine were observed in the DTG/ABC/3TC arm due to known inhibition of tubular creatinine secretion by DTG
256
257
262
257
275
276
237246240249DTG/ABC/3TCART
Number of patients
8
4
BL
16
24
Week
-0,2
-0,1
00,10,20,3DTG/ABC/3TCContinuation ART0,0870,010,087Slide9
Treatment Satisfaction (HIVTSQ)
Adjusted mean change in total score at W24
STRIIVING
Study
: switch to DTG/ABC/3TCSTRIIVING
At baseline, overall treatment satisfaction scores were similar between groups
Adjusted mean difference at W24 (95% CI): 2.4 (1.3, 3.5) ; p < 0.001
DTG/ABC/3TC
Continuation ART
0
1
2
3
4
DTG/ABC/3TC (N = 269)
ART (N = 276)
Trottier
B.
Antivir
Ther. 2017;22(4):295-305.Slide10
STRIIVING Study: switch to DTG/ABC/3TC
Conclusion
Efficacy
Similar virologic response for DTG/ABC/3TC and continuation of current ART at W24, with non-inferioritySuccess rate was maintained through 48 weeks in the early switch groupIn the late switch group, virologic suppression was observed in 92% of subjects on DTG/ABC/3TC (24 weeks post-switch)There were no protocol-defined virologic failure in the study Tolerability 4% of subjects discontinued due to adverse events by W24 in the DTG/ABC/3TC arm vs 0% in the continuation groupThere were no further discontinuations due to adverse events in the early switch arm post-week 24Rates of discontinuation for adverse events in the late switch arm was 2%
113STRIIVINGTrottier B. Antivir Ther. 2017;22(4):295-305.