1. Comparison of NNRTI vs NNRTI
ARV-trial.com
Comparison of NNRTI vs NNRTI
ENCORE
EFV vs RPV
ECHO-THRIVE
STAR
EFV vs ETR
SENSE
DOR vs EFV
DRIVE-AHEAD 1

2. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Design
Randomisation
1 : 1
Open-label
W12
W48
N = 79
ETR 400 mg (4 tablets) QD + EFV placebo + 2 NRTI*
ARV-naïve
HIV RNA > 5,000 c/mL
No R to study drugs
N = 78
EFV 600 mg QD + ETR placebo +
2 NRTI*
Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) at screening
* Open-label NRTI combination selected by investigator : ZDV/3TC BID or ABC/3TC QD or TDF/FTC QD
Primary endpoint
Difference in percentage of patients with at least one grade 1-4 treatment-emergent, drug related neuropsychiatric adverse event by week 12 (adjusted ITT analysis, two-sided test, 90% power)
SENSE
Gazzard B. AIDS 2011;25: 2

3. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Baseline characteristics and patient disposition
ETR + 2 NRTI, N = 79
EFV + 2 NRTI, N = 78
Mean age, years 38
Female
15%
23%
HIV RNA (log10 c/mL), median
4.8
CD4 cell count (/mm3), median
319
273
> 1 IAS-USA NNRTI mutation
12 (15%)*
4 (5%)*
> 1 IAS-USA NRTI mutation 6%
HCV antibody positive
11%
10%
Selected NRTI
TDF/FTC ; ABC/3TC ; ZD/3TC
60% ; 26% ; 14%
Discontinuation by W12
N = 10
N = 8
For adverse event
N = 4
Lost to follow-up
N = 1
Withdrew consent
N = 3
Other reasons
N = 2
* E138A, N = 5, V106I, N = 4, V108I, N = 1, V90I, N = 6
SENSE
Nelson M. AIDS 2011;25:335-40 3

4. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Neuropsychiatric adverse events during 12 weeks
ETR + 2 NRTI
EFV + 2 NRTI P
All events grade 1-4
27.8%
55.1%
< 0.001
Drug-related (primary endpoint)
16.5%
46.2 %
All events grade 2-4
10.1%
19.2%
0.103
Drug-related
5.1%
16.7%
0.019
Nervous system adverse events, all grade
20.2%
33.4%
Dizziness 4%
19%
Psychiatric adverse events, all grade
11 %
39 %
Sleep disorders 9%
32%
Depression
N = 1
N = 4
Serious adverse events : ETR, N = 5, EFV, N = 3
Grade 2-4 skin or subcutaneous AE : ETR, N = 8, EFV, N = 9 ; discontinuation for rash : 4/8 and 4/9
Grade 2-4 elevations in total cholesterol and LDL cholesterol : ETR = 3 and 6 ; EFV = 18 and 13
SENSE
Nelson M. AIDS 2011;25:335-40 4

5. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Response to treatment at week 48
HIV RNA < 40 c/mL 25 50
100 75
75.9
74.4 %
Difference
(95% CI) =
1.6% (-12.0 ; 15.2)
74.1
66.7
ETR + 2 NRTI
EFV + 2 NRTI
ITT, TLOVR
76.8
78.4
Baseline
HIV RNA
< 100,000 c/ml
Non-VF censored analysis
> 100,000 c/ml
All patients
92.3
89.2
83.3
81.8
2.9% (-5.8 ; 11.7)
97.6
93.0
SENSE
Gazzard B. AIDS 2011;25: 5

6. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Protocol-defined criteria for genotype testing
Discontinuation with detectable HIV RNA
HIV RNA decrease < 1 log10 c/mL or > 400 c/mL at week 12
HIV RNA > 50 c/mL at week 48
Virologic failure (2 consecutive HIV RNA > 50 c/mL) by TLOVR algorithm
Resistance data
ETR + 2 NRTI
EFV + 2 NRTI
Virologic failure, n 4 7
Baseline HIV RNA > 100,000 c/mL
3/4
4/7
Presence of resistance mutations, n 3
K103N
V106I + M184I
K103N + M184V + P225H 1
Additional patients genotyped at time of discontinuation (HIV RNA > 50 c/mL), n 2
NNRTI mutation (V90I)
Among patients with baseline IAS-USA NNRTI mutations,
10/10 in the ETR arm and 4/4 in the EFV arm had HIV RNA < 50 c/mL at week 48
SENSE
Gazzard B. AIDS 2011;25: 6

7. SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
ARV-trial.com
SENSE Study: ETR QD + 2 NRTI vs EFV QD + 2 NRTI
Summary
First-line treatment with etravirine 400 mg once daily and two nucleoside reverse transcriptase inhibitors (NRTI) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTI
None of the patients with virological failure in the etravirine arm developed resistance to NNRTI
Etravirine was associated with significantly fewer neuropsychiatric adverse events than EFV. The difference was still statistically significant at the week 48 visit
There were greater rises in lipids in the EFV arm
The risk of grade 2-4 skin or subcutaneous adverse events was similar in the two arms
SENSE
Gazzard B. AIDS 2011;25: 7