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Switch to ATV/r-containing regimen
ATAZIP
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
ATAZIP Study: Switch LPV/r to ATV/r
Design
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– Treatment failure = virologic rebound (2 consecutive HIV-1 RNA ≥ 200 c/mL), lost to follow-up, withdrawn consent, discontinuation for any reason, progression to a new CDC event or death
Switch to ATV/r 300/100 mg qd+ continue NRTIs**
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
Randomisation1 : 1
Open-label
Randomisation1 : 1
Open-label
265 patientsHIV+ ≥ 18 years
On LPV/r + 2 NRTIs ≥ 6 months HIV RNA < 200 c/mL > 6 months*
265 patientsHIV+ ≥ 18 years
On LPV/r + 2 NRTIs ≥ 6 months HIV RNA < 200 c/mL > 6 months* N = 127
N = 121
M24M24
ATV/rN = 121
LPV/rN = 127
Median age, years 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%
NRTIs: TDF + 3TC / TDF + ddI / ZDV + 3TC 20% / 17% / 10% 17% / 9% / 16%
Previous PI failures ≥ 1 21% 20%
Previous PI mutations≥ 1≥ 1 major
36%14%
32%10%
Discontinuation before W48, n (%) 16 (13%) 18 (14%)
For adverse event 6 6
For virologic failure 1 1
Baseline characteristics and patient disposition
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
ATAZIP Study: Switch LPV/r to ATV/r
ATAZIP Study: Switch LPV/r to ATV/r
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)
Virologic reboundTreatment failure
Difference estimate (95% CI)
%
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
Results: W48 outcome
Switch to ATV/r
Continue on LPV/r
5 7
p < 0.0001
6/121 9/127
-2.1% (-8.7%, 4.2%)
0
5
10
15
20
25
30
17
20
0
5
10
15
20
25
30
p = 0.0018
21/121 25/127
%
-2.3% (-12.0%, 8.0%)-2.3% (-12.0%, 8.0%)
ATAZIP Study: Switch LPV/r to ATV/r
0
p = 0.043
1
2
3
-1
-2
-3
TC
/HD
L-C
rat
io
Total cholesterol/HDL cholesterol
Fasting plasma lipids changes from baseline to week 48
Triglycerides Totalcholesterol
LDLcholesterol
HDLcholesterol
0
200
100
-100
-200
-300
p < 0.001
Med
ian
chan
ge
from
bas
elin
e (m
g/dL
)
p < 0.001 p = 0.149 p = 0.185
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
Switch to ATV/r 300/100 qd(N = 121)
Continue on LPV/r 400/100 bid(N = 127)
ATAZIP Study: Switch LPV/r to ATV/r
ATV/r, N = 121 LPV/r, N = 127Death 1 1 (hepatic encephalopathy)
AE leading to discontinuation 5% 5%
Patients with ≥ 1 Grade 3 or 4 AE 11% 16%
Clinical
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
Laboratory
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%)
Adverse events by W48
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
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
Mallolas J, JAIDS 2009;51:29-36ATAZIPATAZIP
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