switch to atv + r-containing regimen - swan - sloat
TRANSCRIPT
Switch to ATV + r-containing regimen- SWAN- SLOAT
Design
Objective– Non inferiority in the proportion of patients with virologic rebound at W48
(upper limit of the 95% CI for the difference = 12%, 90% power)
– Virologic rebound: 2 consecutive HIV-1 RNA ≥ 50 c/mL on study, or last on-study HIV-1 RNA ≥ 50 c/mL followed by study discontinuation
Switch to ATV+r qd*+ continue other ARVs
Continue previous PI regimen+ other ARVs
* ATV 400 mg, or ATV/r 300/100 mg if TDF part of NRTI backbone
Randomisation2: 1
Open-label
Randomisation2: 1
Open-label
419 HIV+ patientsOn stable PI-based regimen ≥ 3 months(PI dosed at least bid and > 3 pills/day)
No history of failure on PI therapy HIV RNA < 50 c/mL ≥ 3 months
CD4 > 50/mm3
419 HIV+ patientsOn stable PI-based regimen ≥ 3 months(PI dosed at least bid and > 3 pills/day)
No history of failure on PI therapy HIV RNA < 50 c/mL ≥ 3 months
CD4 > 50/mm3
N = 141
N = 278
W48W48
SWAN Study: switch PI+r to ATV+r
Gatell J, CID 2007;44:1484-92SWANSWAN
PI use at screening was LPV/r: 37%, NFV: 33%, IDV/r: 10%, IDV: 8%,SQV/r: 6%, SQV: 3%
TDF was part of the ARV regimen in 37 patients (9%) [26 in the ATV group]
SWAN Study: switch PI+r to ATV+r
ATV+r,N = 278
Comparator PI,N = 141
Median age, years 40 41
Female 16% 21%
History of AIDS diagnosis 27% 31%
Hepatitis B and/or C co-infection 32% 31%
Duration of prior PI treatment, mean years 3.4 3.3
HIV-1 RNA at randomisation (baseline), median log10c/mL 1.69 1.69
CD4 cell count at baseline, median/mm3 490 489
Discontinuation before W48, n (%) 40 (14%) 27 (19%)
For adverse event 17 8
For lack of efficacy 1 2
Baseline characteristics and patient disposition
Gatell J, CID 2007;44:1484-92SWANSWAN
Gatell J, CID 2007;44:1484-92SWANSWAN
SWAN Study: switch PI+r to ATV+r
Virologic rebound (HIV-1 RNA ≥ 50 c/mL) Treatment failure
0
5
10
15
35
40
302520
p = 0,004
p = 0,53
p < 0,001
p = 0,004
7%
8%
5%
16%
11%
22%21%
34%
19/278
22/141 12/150
8/76 7/128
14/65 59/278
48/141Differenceestimate(95% CI)
-8.8 (-14.8 ; -2.7) -2.5 (-10.4 ; 5.3) -16.1 (-25.4 ; -6.8) -12.8 (-21.7 ; -4.0)
ATV group Comparator PI group
Patients on PI/rat screening
All patientsPatients on unboosted
PI at screening
%
SWAN Study: switch PI+r to ATV+r
Gatell J, CID 2007;44:1484-92SWANSWAN
ATV group Comparator PI group
ATV groupATV group
ComparatorPI groupComparatorPI group
278141
254 231239 143121 101110 74
258278 231240 143122141 101110 74
0
20
40
60
80
100
12Baseline 3624 48
Weeks
Patients not experiencingvirologic rebound,%
Hazard Ratio estimate (95% CI):0.42 (0.22-0.79) ; p = 0.007
Patients not experiencingtreatment failure,%
20
40
60
80
100
12Baseline 3624 48
Weeks
Hazard Ratio estimate (95% CI):0.59 (0.40-0.87) ; p = 0.008
SWAN Study: switch PI+r to ATV+r
Gatell J, CID 2007;44:1484-92SWANSWAN
HDL-C,high density lipoprotein cholesterol ; LDL-C, low-density lipoprotein cholesterol ; PI, protease inhibitor ; TC, total cholesterol
Mean changes from baseline in lipid parameters at W48
ATV group Comparator PI group
TC HDL-C Fasting TG Non-HDL-C
Mean mg/dL at baselineMean mg/dL at baseline
Mean mg/dL at Week 48Mean mg/dL at Week 48
123
108
135
133
212
181
220
216
50
51
50
49
203
137
201
215
162
132
171
168
Fasting LDL-C
-40
-30
-10
0
10
-20p = 0.18
p < 0.001
p = 0.62
p < 0.001
p < 0.001
-12%
-5%-3%
-15%
-3%-1%
-33%
-18%
-3%
9%
AST and ALT elevations were more frequent in patients with hepatitis co-infection
SWAN Study: switch PI+r to ATV+r
ATV group Comparator PIDeath 0 5
Serious adverse event 27 (10%) 9 (6%)
Discontinuation because of adverse event 17 (6%) 8 (6%)
Scleral icterus 8 (3%) 0
Jaundice 7 (3%) 0
Abdominal pain 6 (2%) 2 (2%)
Grade 3-4 ALT elevation 12 (4%) 8 (6%)
Grade 3-4 AST elevation 7 (3%) 4 (3%)
Grade 3-4 total bilirubin elevation 116 (43%) 4 (3%)
Gatell J, CID 2007;44:1484-92SWANSWAN
Adverse events by W48
SWAN Study: switch PI+r to ATV+r
Conclusions– Switching to a simplified PI-based regimen containing ATV
provided better maintenance of virologic suppression with lower rates of virologic rebound and treatment failure than those observed with continued, unmodified therapy
– Safety and tolerability were similar in both groups
• But lipid parameters improved in the ATV group
• Hyperbilirubinemia was frequent on ATV
Gatell J, CID 2007;44:1484-92SWANSWAN