1. ARV-trial.com
Switch to DTG/ABC/3TC
STRIIVING
NEAT 022 1

2. STRIIVING Study: switch to DTG/ABC/3TC
Design
Randomisation *
1 : 1
Open-label
W24
W48
HIV+ ≥ 18 years
HIV RNA < 50 c/mL
On 2 NRTI + PI/r or NNRTI or INSTI stable ≥ 6 months
HLA-B*5701 negative
HBs Ag negative
N = 275
Switch to DTG/ABC/3TC
Continue current ART
Switch to DTG/ABC/3TC
N = 278
* Randomisation was stratified by 3rd agent (PI, INSTI or NNRTI)
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
STRIIVING
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3. STRIIVING Study: switch to DTG/ABC/3TC
ARV-trial.com
STRIIVING Study: switch to DTG/ABC/3TC
Baseline characteristics and patient disposition
DTG/ABC/3TC
N = 275
Continuation of current ART (deferred switch)
N = 278
Median age, years 45 47
Female, % 14
Hepatitis C coinfection, % 8 5
Median time on current ART, months 54 51
CD4 cell count (/mm3), median
618
597
ART at randomisation, % PI
NNRTI
INSTI
TDF/FTC backbone 43 32 25 76 42 31 27 79
Discontinuation, N
W0-W24 / W24-W48
For adverse event
For protocol deviation
Lost to follow-up
For other reasons
36 / 9
10 / 0
15 / 0
3 / 5
8 / 4
33 / 14
0 / 4
17 / 1
3 / 3
13 / 6
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4. STRIIVING Study: switch to DTG/ABC/3TC
HIV RNA < 50 c/mL (ITT-e)
* Analysis restricted to patients
with deferred switch 85 1 14 88 10 83
< 1 17 92 7 20 40 60 80
100 %
DTG/ABC/3TC
Immediate switch D1-W24 (N = 275)
At week 24
- Lower bound for the
adjusted difference : %
(non-inferiority), by ITT-E
- Success in 93 % in both
groups in the per-protocol
analysis (difference : - 0.2;
95% CI : to 4.6)
Continuation cART D1-W24 (N = 278)
DTG/ABC/3TC
Immediate switch D1-W48 (N = 275)
DTG/ABC/3TC
Deferred switch W24-W48 (N = 244 *)
Virologic success
Virologic non response
No virologic data
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/mL
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5. STRIIVING Study: switch to DTG/ABC/3TC
111
Adverse events at W24, n (%)
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)
Discontinuation for adverse event
11 (4)
Adverse event in ≥ 5% in either group
Cough
14 (5)
Diarrhea
17 (6)
Fatigue
19 (7)
3 (1)
Headache
13 (5)
Nausea
27 (10)
Upper respiratory tract infection
21 (8)
20 (7)
Psychiatric
35 (13)
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6. STRIIVING Study: switch to DTG/ABC/3TC
112
Adverse events leading to discontinuation of DTG/ABC/3TC (N = 10)
Grade
Onset
Prior ARV (3rd drug) 1
Insomnia 2 W1
LPV/r
Diarrhea, flatulence, rash,
Abdominal pain, anxiety, nausea, body ache
RPV 3
Euphoric mood,
Headache
ATV/r 4
Abdominal cramps, chills, diarrhea, dizziness, headache
RAL 5
Pruritus
NFV 6
Upper abdominal pain, diarrhea
Fatigue1, malaise
Flu-like syndrome
Depression
Profuse sweating, change in body odor W9
W12
W17
NVP 7
Nasal congestion
Worsening fatigue
Nausea W2
EVG/c 8
Alopecia               W4 9
Fatigue1 W8
DRV/r 10
Homicide1 NA
W10
1 Not drug-related
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7. STRIIVING Study: switch to DTG/ABC/3TC
Fasting Lipids, mean mg/dL
DTG/ABC/3TC at Baseline
Continuation ART at Baseline
DTG/ABC/3TC at W24
Continuation ART at W24
140
100 40
200 20 60 80
120
160
180
Total cholesterol
HDL
LDL
Triglycerides
3.5
2.5 1 5
0.5
1.5 2 3 4
4.5
Total cholesterol:HDL ratio
Total cholesterol
HDL - cholesterol
LDL- cholesterol
Triglycerides
Total cholesterol: HDL ratio
DTG/ABC/3TC
ART
Change from baseline at W24 (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)
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8. STRIIVING Study: switch to DTG/ABC/3TC
Mean change from baseline in serum creatinine (mg/dL) through 24 weeks
256
257
262
275
276
237
246
240
249
DTG/ABC/3TC
ART
Number of patients 8 4 BL 16 24
Week
-0,2
-0,1
0,1
0,2
0,3
Continuation ART
0,087
0,087
0,01
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
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9. STRIIVING Study: switch to DTG/ABC/3TC
Treatment Satisfaction (HIVTSQ)
Adjusted mean change in total score at W24
Adjusted mean difference at W24 (95% CI): 2.4 (1.3, 3.5) ; p < 0.001
DTG/ABC/3TC
Continuation ART 1 2 3 4
DTG/ABC/3TC (N = 269)
ART (N = 276)
At baseline, overall treatment satisfaction scores were similar between groups
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Conclusion
Efficacy
Similar virologic response for DTG/ABC/3TC and continuation of current ART at W24, with non-inferiority
Success rate was maintained through 48 weeks in the early switch group
In 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 group
There were no further discontinuations due to adverse events in the early switch arm post-week 24
Rates of discontinuation for adverse events in the late switch arm was 2%
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