1. ARV-trial.com
Switch to FTC + ddI + EFV
ALIZE 1

2. ALIZE Study: Switch PI+r to FTC + ddI + EFV
Design
Randomisation
1 : 1
Open-label
W48
N = 177
389 HIV+ adults
ARV with PI±r + 2 NRTIs
HIV-1 RNA < 400 c/mL > 6 months
CD4 cell count ≥ 100/mm3
NNRTI-naïve
Continue PI-based regimen
N = 178
Switch to FTC + ddI + EFV qd
Objective
Non inferiority in the proportion of patients with HIV-1 RNA < 400 c/mL at W48 (Intent-to-treat analysis, missing = failure) ; upper limit of the 95% CI for the difference = 15%, 80% power
ALIZE
Molina JM, JID 2005;191:830-9

3. ALIZE Study: Switch PI+r to FTC + ddI + EFV
ARV-trial.com
ALIZE Study: Switch PI+r to FTC + ddI + EFV
Baseline characteristics and patient disposition
Continuation
of PI-based
Regimen
N = 177
FTC + ddI + EFV
N = 178
Median age, years 41
Female
13%
15%
History of AIDS diagnosis
25%
28%
CD4 cell count, median /mm3
547
509
HIV-1 RNA < 50 c/mL
89%
92%
PI: IDV ; NFV ; RTV ; PI/r
49% ; 37% ; 5% ; 7%
37% ; 38% ; 6% ; 15%
NRTIs: ZDV + 3TC ; d4T + 3TC ; d4T + ddI
43% ; 44% ; 9%
42% ; 46% ; 8%
Prior suboptimal therapy with NRTI
45%
47%
Discontinuation before W48, n (%)
37 (21%)
24 (13%)
For adverse event 17 16
For virologic failure 1 5
ALIZE
Molina JM, JID 2005;191:830-9 3

4. ALIZE Study: Switch PI+r to FTC + ddI + EFV
ARV-trial.com
ALIZE Study: Switch PI+r to FTC + ddI + EFV
Outcome at Week 48
Virologic response
Continuation PI
FTC + ddI + EFV
93.1 96
HIV-1 RNA
< 200 c/mL
< 50 c/mL % 20 40 60 80
100
Non inferiority
Upper bound of
the 95% CI for
the ≠: 2,6%
the ≠: 1.2%
87.6
90.5
p < 0.05
log rank test 79 87
ITT,
M = F
On Treatment, M = F
Kaplan-Meier (ITT)
M= F: missing= failure
Patients who had received prior suboptimal ARV therapy with mono- or dual-NRTIs alone were not a higher risk of virologic failure (10% vs 11%)
ALIZE
Molina JM, JID 2005;191:830-9 4

5. ALIZE Study: Switch PI+r to FTC + ddI + EFV
CD4 response, resistance and safety
No differences in median CD4 cell counts over time between groups
13/14 virologic failures had a genotype (5 in the FTC + ddI + EFV group, 8 in the PI group)
FTC + ddI + EFV: R to EFV (K103N, N = 4, L100I, N = 2) + FTC (M184V) = 5/5 ; L74 V in 1/5
PI group: major PI resistance mutation = 3/8, M184V = 5/8
Trend towards a higher overall incidence of grade 2 to 4 adverse events in the FTC + ddI + EFV group (48% vs 38%, p = 0.06)
Related to neurosensorial reactions in first 4 weeks
And to higher increases in aminotransferase levels
Discontinuation for adverse events was similar in both groups: 10% vs 9%, for PI and FTC + ddI + EFV group, respectively
Lipoatrophy increased in the PI group (46% at baseline vs 60% at W48) and remained stable in the FTC + ddI + EFV group (43% vs 42%), p <
Full adherence (100% of the pills taken during the 4 days before all visits) through W48 was 63% vs 82%, respectively (p = )
ALIZE
Molina JM, JID 2005;191:830-9

6. ALIZE Study: Switch PI+r to FTC + ddI + EFV
Median change from baseline in fasting lipids (mg/dL)
Total cholesterol PI
FTC + ddI + EFV
171
160
163
164
159
155
173
168
166
169 35 30 20 25 10 15 5
-10 -5
-20
-15
-25 4 8 12 16 28 32 36 40 44 48 24
Weeks
Continuation PI
FTC + ddI + EFV
Triglycerides
HDL cholesterol 20 15 10 5
-10 -5 4 8 12 16 28 32 36 40 44 48 24 PI
FTC + ddI + EFV
166
153
157
158
152
143
171
162
164
160
159
Weeks PI
FTC + ddI + EFV 60 50 30 40 10 20
-10
-30
-20
-50
-40
-60 4 8 12 16 28 32 36 44 48 24
173
168
166
171
167
165
160
164
163
158
154
Weeks
ALIZE
Molina JM, JID 2005;191:830-9

7. ALIZE Study: Switch PI+r to FTC + ddI + EFV
Conclusions
Switching a PI-based regimen, in patients with virologic suppression, to a convenient once-daily combination of FTC + ddI + EFV is associated with
Sustained virologic suppression
Some adverse events, mainly neurosensorial and hepatic, usually not treatment-limiting
Improvement in HDL cholesterol
No worsening of lipoatrophy
ALIZE
Molina JM, JID 2005;191:830-9