STRATEGYPI Study STRATEGYNNRTI Study Design Endpoints Primary proportion of patients maintaining HIV RNA lt 50 cmL at W48 mITT snapshot noninferiority if lower margin of a twosided 95 CI for the difference 12 85 power If noninferiority and lower margin gt 0 assessme ID: 616654
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Slide1
Switch to EVG/c/FTC/TDF
STRATEGY-PI
Study
STRATEGY-NNRTI
StudySlide2
Design
Endpoints
Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (mITT, snapshot) ; non-inferiority if lower margin of a two-sided 95% CI for the difference = -12%, 85% power. If non-inferiority and lower margin > 0, assessment for superiority
Secondary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (TLOVR algorithm), CD4, safety, tolerability to W96
Switch to EVG/c/FTC/TDF
Continue NNRTI + FTC + TDF
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTI
Randomisation*
2 : 1Open-label
HIV+ ≥ 18 yearsOn FTC + TDF + NNRTI HIV RNA < 50 c/mL > 6 monthsNo virologic failureGenotype testing before ART withno resistance to study drugsIntegrase inhibitor naïveeGFR > 70 mL/mim
N = 147
N = 292
W48
W96
* Randomisation stratified by EFV use at screening
STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide3
STRATEGY-NNRTI Study: Switch NNRTI to EVG/c
EVG/c/FTC/TDF
N = 291
NNRTI + FTC + TDF
N = 143
Median age, years
43
39
Female
8%
6%
Time since HIV diagnosis, median years
5
5
On first ARV regimen
90%
91%
NNRTI at randomisation
Efavirenz
(
coformulated
EFV/FTC/TDF)
80% (76%)
74% (70%)
Nevirapine16%19%Rilpivirine3%7%Etravirine1%0CD4 cell count (/mm3), median561562Hepatitis B / hepatitis C coinfection2% / 4%2% / 1%Discontinuation by W482218
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTI
Baseline characteristics and patient dispositionSlide4
Virologic outcome at W48 (mITT, snapshot)
93
88
Difference (95% CI)
= 5.3% (-0.5 to 12.0)
1
1
N = 3
N = 1
6
11
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTI
EVG/c/FTC/TDF
NNRTI + FTC + TDF
%
0
20
406080
100
HIV RNA
< 50 c/mL
HIV RNA
≥ 50 c/mL
No virologicdataSTRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide5
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTI
HIV RNA < 50 c/mL
Sensitivity and secondary analysis
EGV/c/FTC/TDF
NNRTI + FTC + TDF
Per-proctol
99%
99%
Difference
: 0.1% (95% CI: - 2.1 to 3.5)
ITT-TLOVR
92%
87%
Difference
: 5.0% (95% CI: -1.1 to 12.1)
One participant in each group met the criteria for resistance testing (HIV RNA
>
400 c/mL at virologic failure or early discontinuation)
No emergence of resistance
Both remained on study treatment and achieved HIV RNA < 50 c/mL after W48
STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide6
Virologic sucess overall and by subgroup at W48 (mITT)
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTI
Overall
Age < 40
years
Age
>
40
years
Male
Female
White
Non-white
Efavirenz
Non-
efavirenz
On first
regimen
at
baseline
On second
regimen
at
baseline010203040
50
60
70
80
90
100
Virological
success
(%)
271/290
126/143
107/114
62/74
164/176
64/69
251/267
119/134
20/23
7/9
216/230
99/109
55/60
27/34
214/231
91/106
57/59
35/37
245/262
114/130
25/27
11/12
n/N
Favours
not
switching
Switch group
No-switch group
-20
-10
0
10
20
30
40
50
Difference
(%)
Favours
switching
STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide7
Adverse events and grade 3-4 laboratory abnormalities
* neuromuscular symptoms, suicide, dysgueusia, prurigo, Fanconi syndrome, increased creatinine
** altered mood
Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTISTRATEGY-NNRTI Study: Switch NNRTI to EVG/c
EVG/c/FTC/TDF
NNRTI + FTC + TDF
Any
adverse
event
,
81%
75%
Grade 3 or 4 AE
7%
6%
Serious
adverse
event
5%
4%
Discontinuation because of AE
N = 6 (2%)*
N = 1 (1%)**
Death
N = 1
0
AE occurring more frequently in one group
14%
23%
Headache
(p = 0.03)
3%
1%
Nausea
(p = 0.05)
2%
6%
Cough
(p= 0.04)
2%
1%
Fatigue (p = 0.02)
2%
1%Slide8
STRATEGY-NNRTI Study: Switch NNRTI to EVG/c
Other safety data
Incidence and prevalence of headache and nausea became similar between groups by week 12
Grade 3-4 laboratory abnormalities : 10% in the switch group vs 14% in the no-switch groupCreatinine increase in switch group at week 4, stabilizing up to week 48 (median +11 mmol
/L)Small decrease in HDL-cholesterol in the switch group vs no change in the no-switch groupIn the subgroup switched form EFV + FTC + TDF to EVG/c/FTC/TDFImprovement in lipidsHIV Symptom Index : improvement of CNS symptomsHigher treatment satisfaction score at W4 and W24Pozniak A. Lancet Infect Dis 2014;14:590-9
STRATEGY-NNRTISlide9
STRATEGY-NNRTI Study: Switch NNRTI to EVG/c
Conclusion
Coformulated
EVG/c/FTC/TDF is non-inferior to continuing an existing regimen of NNRTI plus FTC and TDF in virologically suppressed, HIV-infected adults with no history of virological failure or resistance to FTC or TDF.Low frequency of virologic
failure and absence of emergent resistance in the group switched to EVG/c/FTC/TDF Rare discontinuations because of adverse eventsFatigue, cough, headache and nausea were more frequent in the switch group ; Rates of CNS symptoms decreased in patients switched from EFVIncrease in creatinine similar to that of phase 3 of EGV/c/FTC/TDFModerate improvement in lipids in patients switched from EFVEVG/c/FTC/TDF is a switch option in virologically suppressed patients with no history of virological failure on an NNRTI regimen, when its continuation is not suitable
Pozniak A. Lancet Infect Dis 2014;14:590-9STRATEGY-NNRTI