Transcript AI266073 Study

Switch to TDF/FTC/EFV
 AI266073 Study
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
 Design
Randomisation*
2:1
Open-label
306 HIV+ ≥ 18 years
ARV with PI+r + ≥ 2 NRTIs or NNRTI +
≥ 2 NRTIs (exclusion of patients
on TDF + FTC + EFV)
No history of prior virologic failure
HIV-1 RNA < 200 c/mL > 3 months
Creatinine clearance ≥ 60 mL/min
W48
N = 97 Continue Stable Baseline
Regimen (SBR)
N = 203 Switch to TDF/FTC/EFV qd fdc
(single tablet)
fdc = fixed drug combination
* Randomisation stratified on the use of PI or NNRTI
(53% patients on PI, 47% on NNRTI)
 Objective
‒ Non inferiority in the proportion of patients with HIV-1 RNA < 200 c/mL at W48
(Intent-to-treat analysis, non completer = failure, TLOVR algorithm) ;
lower limit of the 95% CI for the difference = -15%, 80% power
AI266073
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
Baseline characteristics and patient disposition
Continuation of SBR
N = 97
TDF/FTC/EFV
N = 203
43
43
Female
14%
11%
HIV-1 RNA < 50 c/mL
98%
96%
CD4 cell count, median/mm3
515
517
Duration of current ARV regimen, median years
3.1
2.6
Current ARV therapy as first regimen
88%
88%
Hepatitis B or C coinfection
1%
7%
40% / 32% / 23%
37% / 42% / 23%
12 (12%)
22 (11%)
For adverse event
1
10
For virologic failure
0
1
Median age, years
Background NRTI at enrolment: TDF/ZDV/ABC
Discontinuation before W48, n (%)
AI266073
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
Outcome at Week 48
Virologic response (ITT, NC = F, TLOVR) for the whole population
and by prior treatment stratum
%
100
85
87
88
89
203
97
203
92
82
87
83
80
60
40
20
0
N= 97
HIV-1 RNA
< 50 c/mL
95% CI
for the difference
= -5.9 ; 11.1
HIV-1 RNA
< 200 c/mL
95
52
108
HIV-1 RNA < 50 c/mL
Prior NNRTI
Prior PI
95% CI
for the difference
= -6.7 ; 8.8
SBR
AI266073
45
95% CI
for the difference
= -3.1 ; 21.8
95% CI
for the difference
= -14.8 ; 8.4
TDF/FTC/EFV
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
 Other endpoints
– Virologic failure
• SBR, N = 1 (1.03%)
• TDF/FTC/EFV, N = 3 (1.48%)
– No significant changes in CD4 cell counts within or between
treatment arms
– Nervous System and Psychiatric Symptoms
• Nervous System Symptoms = SBR: 13% vs TDF/FTC/EFV: 22%
• Psychiatric Symptoms = SBR: 8% vs TDF/FTC/EFV: 28%
• Study drug discontinuation, N = 5, all in TDF/FTC/EFV group
(prior PI stratum)
– Renal Adverse events
• Discontinuation for increase in creatinine, N = 1, on TDF/FTC/EFV
• Grade 1 treatment-emergent creatinine elevations = SBR: 3%
vs TDF/FTC/EFV: 2%. No Grade ≥ 2 elevation of creatinine
AI266073
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
Changes in glomerular filtration rate* (mL/min/1.73 m2)
120
120
100
100
80
80
60
60
40
40
20
20
0
0
0 4
12
24
36
Study week
48
0 4
12
24
36
Study week
48
TDF/FTC/EFV 203 200
196
188
182
181
129 127
125
121
120
120
SBR
95
92
89
87
58
57
54
51
50
97
95
* Evaluated by the MDRD equation
AI266073
SBR
57
TDF/FTC/EFV
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
 Fasting lipid changes
– Overall, no significant differences were seen between treatment arms for
fasting total cholesterol and LDL cholesterol
– No change in HDL cholesterol overall or in the prior NNRTI stratum
– Significant increase in HDL cholesterol in the TDF/FTC/EFV group vs SBR
group for patients in the prior PI regimen
– For triglycerides, decrease of levels were significantly higher in the
TDF/FTC/EFV group and was greatest in the prior PI stratum
 Patients’ questionnaires
– Preference of TDF/FTC/EFV over the previous regimen
– TDF/FTC/EFV regimen considered easier than SBR (p < 0.001)
– Patients in the TDF/FTC/EFV group had more symptoms of dizziness or
light-headedness compared with the SBR, at W4 (p = 0.018)
– Improvement in diarrhoea and loose bowel movements in the
TDF/FTC/EFV group for patients with prior PI-based regimen (p = 0.002)
AI266073
DeJesus E, JAIDS 2009;51:163-74
AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
 Conclusions
– Patients with stable ARV treatment and virologically
suppressed on NNRTI- or PI-based therapy maintained
high rates of virological suppression after simplification to a
single-tablet regimen of TDF/FTC/EFV
– TDF/FTC/EFV was virologically non inferior to maintenance
of prior suppressive ARV regimen
– Patients on prior PI-based therapy were more likely to
experience transient nervous system and psychiatric
symptoms ; for 2% of patients, these adverse events
were treatment-limiting
AI266073
DeJesus E, JAIDS 2009;51:163-74