1. ARV-trial.com
Switch to TDF/FTC/EFV
AI Study 1

2. AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
Design
Randomisation*
2 : 1
Open-label
W48
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
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

3. AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
ARV-trial.com
AI Study: Switch PI or NNRTI to TDF/FTC/EFV
Baseline characteristics and patient disposition
Continuation of SBR
N = 97
TDF/FTC/EFV
N = 203
Median age, years 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%
Hepatitis B or C coinfection 1% 7%
Background NRTI at enrolment: TDF/ZDV/ABC
40% / 32% / 23%
37% / 42% / 23%
Discontinuation before W48, n (%)
12 (12%)
22 (11%)
For adverse event 1 10
For virologic failure
AI266073
DeJesus E, JAIDS 2009;51:163-74

4. AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
ARV-trial.com
AI 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
SBR
TDF/FTC/EFV 88 89
HIV-1 RNA
< 50 c/mL
HIV-1 RNA < 50 c/mL % 20 40 60 80
100
95% CI for the difference = -5.9 ; 11.1
< 200 c/mL
95% CI for the difference = -6.7 ; 8.8 85 87
95% CI for the difference = -3.1 ; 21.8
95% CI for the difference = ; 8.4
Prior NNRTI
Prior PI 82 92 83 N= 97
203 45 95 52
108
AI266073
DeJesus E, JAIDS 2009;51:163-74

5. 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

6. AI266073 Study: Switch PI or NNRTI to TDF/FTC/EFV
Changes in glomerular filtration rate* (mL/min/1.73 m2)
TDF/FTC/EFV
SBR
203 97
200
182
188
181 95 89 92 87
196
129 58
127
120
121 57 51 54 50
125 20 40 60 80
100 4 12 24 36 48
Study week
* Evaluated by the MDRD equation
AI266073
DeJesus E, JAIDS 2009;51:163-74

7. 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

8. 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