the slides - ARV

Report
Switch to EVG/c/FTC/TDF
 STRATEGY-PI Study
 STRATEGY-NNRTI Study
STRATEGY-PI Study: Switch PI/r to EVG/c
 Design
HIV+ ≥ 18 years
On FTC + TDF + PI/r
HIV RNA < 50 c/mL > 6 months
No virologic failure
Genotype testing before ART with
no resistance to study drugs
Integrase inhibitor naïve
eGFR > 70 mL/min
Randomisation
2:1
Open-label
N = 293
N = 145
W48
W96
Switch to EVG/c/FTC/TDF
Continue PI/r + FTC + TDF
 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
STRATEGY-PI
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
Baseline characteristics and patient disposition
EVG/c/FTC/TDF
N = 293
PI/r + FTC + TDF
N = 140
41
40
15%
14%
4
4
77%
83%
Atazanavir
42%
37%
Darunavir
39%
43%
Lopinavir
17%
16%
Fosamprenavir
2%
4%
Saquinavir
1%
0
564
585
Hepatitis B / hepatitis C coinfection
3% / 7%
2% / 7%
Discontinuation by W48
25 (8.5%)
26 (18.6%)
Median age, years
Female
Time since HIV diagnosis, median years
On first ARV regimen
PI at randomisation
CD4 cell count (/mm3), median
STRATEGY-PI
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
Virologic outcome at W48 (mITT, snapshot)
EVG/c/FTC/TDF
HIV RNA
< 50 c/mL
PI/r + FTC + TDF
HIV RNA
≥ 50 c/mL
No virologic
data
%
100
94
87
80
60
40
20
6
1
0
Difference (95% CI)
= 6.7% (0.4 ; 13.7)
STRATEGY-PI
12
1
N=2 N=2
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
HIV RNA < 50 c/mL
Sensitivity and secondary analysis
Per-proctol
EGV/c/FTC/TDF
PI/r + FTC + TDF
99.5%
99.2%
Difference: 0.1% (95% CI = - 2.1 ; 3.7)
ITT-TLOVR
91.7%
84.2%
Difference: 7.6% (95% CI = 0.9 ; 15.0)

No participants met the criteria for resistance testing (HIV RNA > 400 c/mL at
virologic failure or early discontinuation)
STRATEGY-PI
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
Virologic sucess overall and by subgroup at W48 (mITT)
n/N
272/290
121/139
122/130
61/68
150/160
60/71
231/247
103/120
41/43
18/19
217/231
98/113
53/57
22/24
114/121
41/51
107/113
55/60
45/49
20/23
213/225
104/115
53/59
16/23
Overall
Age < 40 years
Age > 40 years
Male
Female
White
Non-white
Atazanavir
Darunavir
Lopinavir
On first regimen
at baseline
On second regimen
at baseline
0
STRATEGY-PI
10 20 30 40 50 60 70 80 90 100
Virological success (%)
Switch group
No-switch group
-50 -40 -30
-20 -10 0
10 20 30 40 50
Difference (%)
Favours not switching
Favours switching
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
Adverse events and grade3-4 laboratory abnormalities
EVG/c/FTC/TDF
PI/r + FTC + TDF
79%
74%
4%
8%
6%
6%
N = 6 (2%)
N = 4 (3%)
0
N=1
14%
23%
Gamma-GT > 5 x ULN
3%
1%
CK ≥ 10 x ULN
2%
6%
ALAT > 5 x ULN
2%
1%
Haematuria
2%
1%
0
12%
Any adverse event,
Grade 3 or 4 AE
Serious adverse event
Discontinuation because of AE
Death
Any Grade 3 or 4 laboratory abnormality
Bilirubin > 2.5 x ULN



Improvement in lipids in the switch group
HIV Symptom Index : rates of diarrhea and bloating decreased in the switch group
Higher tretament satisfaction scores in the switch group
STRATEGY-PI
Arribas J.R. Lancet Infect Dis 2014;14:581-9
STRATEGY-PI Study: Switch PI/r to EVG/c
 Conclusion
– Coformulated EVG/c/FTC/TDF is an effective, safe, and tolerable
simplification from a PI/r plus FTC and TDF regimen 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 events
– Nausea more frequent in the switch group ; diarrhea and bloating
improved
– Small increase in creatinine, moderate improvement in lipids
– EVG/c/FTC/TDF is a switch option in virologically suppressed patients
with no history of virological failure who want to simplify their existing
PI/r regimen, or who have concerns about the long-term safety and
side-effects of their existing regimen
STRATEGY-PI
Arribas J.R. Lancet Infect Dis 2014;14:581-9

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