Transcript the slides - ARV

Switch to ATV/r-containing regimen
- ATAZIP
ATAZIP Study: Switch LPV/r to ATV/r
 Design
Randomisation
1:1
Open-label
M24
N = 121 Switch to ATV/r 300/100 mg qd
265 patients
HIV+ ≥ 18 years
On LPV/r + 2 NRTIs ≥ 6 months
HIV RNA < 200 c/mL > 6 months*
+ continue NRTIs**
N = 127 Continue LPV/r 400 /100 mg bid
+ NRTIs**
* Not more than 2 previous virologic failure on PI and if genotype performed < 5 mutations
** Switch in NRTI not counted as failure
 Endpoints
– Primary: non inferiority in the proportion of patients with treatment failure at
W48 (intent-to-treat analysis), lower limit of the 95% CI for the difference =
-12.5%, 80% power
– Treatment failure = virologic rebound (2 consecutive HIV-1 RNA ≥ 200 c/mL),
lost to follow-up, withdrawn consent, discontinuation for any reason,
progression to a new CDC event or death
ATAZIP
Mallolas J, JAIDS 2009;51:29-36
ATAZIP Study: Switch LPV/r to ATV/r
Baseline characteristics and patient disposition
ATV/r
N = 121
LPV/r
N = 127
42
43
Female
20%
21%
History of AIDS diagnosis
40%
57%
Hepatitis C co-infection
36%
27%
CD4 cell count at baseline < 200 /mm3
8%
10%
20% / 17% / 10%
17% / 9% / 16%
Previous PI failures ≥ 1
21%
20%
Previous PI mutations
≥1
≥ 1 major
36%
14%
32%
10%
16 (13%)
18 (14%)
For adverse event
6
6
For virologic failure
1
1
Median age, years
NRTIs: TDF + 3TC / TDF + ddI / ZDV + 3TC
Discontinuation before W48, n (%)
ATAZIP
Mallolas J, JAIDS 2009;51:29-36
ATAZIP Study: Switch LPV/r to ATV/r
Results: W48 outcome
Treatment failure
%
%
Virologic rebound
30
30
p = 0.0018
25
Switch to ATV/r
Continue on LPV/r
25
20
20
20
15
17
10
10
5
5
0
0
21/121
25/127
-2.3% (-12.0%, 8.0%)


15
p < 0.0001
7
5
6/121
Difference estimate (95% CI)
9/127
-2.1% (-8.7%, 4.2%)
Time to treatment failure and time to virological failure did not differ between groups
The median changes in CD4 count at 48 weeks were +27 cells/mm3 (IQR: -42 to 119)
with ATV/r and +48 cells/mm3 (IQR: -5 to 112) with LPV/r (p = 0.315)
ATAZIP
Mallolas J, JAIDS 2009;51:29-36
ATAZIP Study: Switch LPV/r to ATV/r
3
200
p < 0.001
p < 0.001
100
p = 0.149
-100
1
0
-1
-2
-3
-200
Triglycerides
Total
cholesterol
LDL
HDL
cholesterol cholesterol
Switch to ATV/r 300/100 qd
(N = 121)
ATAZIP
p = 0.185
0
-300
p = 0.043
2
TC/HDL-C ratio
Median change from baseline (mg/dL)
Fasting plasma lipids changes from baseline to week 48
Total cholesterol/
HDL cholesterol
Continue on LPV/r 400/100 bid
(N = 127)
Mallolas J, JAIDS 2009;51:29-36
ATAZIP Study: Switch LPV/r to ATV/r
Adverse events by W48
ATV/r, N = 121
LPV/r, N = 127
1
1 (hepatic encephalopathy)
AE leading to discontinuation
5%
5%
Patients with ≥ 1 Grade 3 or 4 AE
11%
16%
Cardiovascular
N=1
N=1
Digestive
N=2
N =1
Osteomuscular
N=0
N=1
Hematologic
N=0
N=1
Hepatic
N=1
N=1
Respiratory
N=1
N=0
Transaminases
N=6
N=2
Total cholesterol
N=4
N=7
Triglycerides
N=0
N = 13
Bilirubin > 2.5 mg/dL
N = 66 (55%)
N = 6 (5%)
Bilirubin > 5 mg/dL
N = 21 (17%)
N = 2 (2%)
Death
Clinical
Laboratory
ATAZIP
Mallolas J, JAIDS 2009;51:29-36
ATAZIP Study: Switch LPV/r to ATV/r
 Conclusions
– Switching to a simplified PI-based regimen containing
ATV/r provides virological suppression and treatment
failure similar to those observed with continued unmodified
therapy with LPV/r
– Safety and tolerability profile were similar in both groups
– Improved lipid parameters were observed in the ATV/r arm
– High incidence of hyperbilirubinemia occurred in the ATV/r
arm
– Switching patients with virologic suppression on LPV/r to
once-daily ATV/r can provide an effective and well-tolerated
treatment option
ATAZIP
Mallolas J, JAIDS 2009;51:29-36