1. Comparison of NNRTI vs PI/r
ARV-trial.com
Comparison of NNRTI vs PI/r
EFV vs LPV/r vs EFV + LPV/r
A5142
Mexican Study
NVP vs ATV/r
ARTEN
EFV vs ATV/r
A5202 1

2. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Design
Randomisation*
1:1:1
Open-label
W48
W144
> 18 years, ARV-naïve
CD4 cell count
< 400/mm3 for males,
<250/mm3 for females
Creatinine clearance
> 50 mL/min
N = 188
NVP 400 mg QD** + TDF/FTC
N = 188
NVP 200 mg BID** + TDF/FTC
N = 193
ATV/r mg QD + TDF/FTC
* Randomisation stratified by HIV RNA (< or > 100,000 c/mL) and CD4 (> or < 50/mm3) at screening
** Lead-in of NVP 200 mg QD for the first 2 weeks
Objective
Non inferiority of NVP (combined groups) compared to ATV/r for primary endpoint: % HIV RNA < 50 c/mL at W24, W36 and W48 by intention to treat with non completers equals failures, (2-sided significance level of 5%, lower margin of the 95% CI for the difference = -12%, 80% power)
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 2

3. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Baseline characteristics and patient disposition
NVP QD
N = 188
NVP BID
ATV/r
N = 193
Mean age 38 40
Female
19%
13%
16%
HIV RNA (log10 c/mL), mean
5.1
HIV RNA > 100,000 c/mL
62.8%
65.8%
CD4 cell count (/mm3), mean
177
187
188
CD4 < 50 per mm3
7.4%
9.0%
6.2%
Hepatitis B / hepatitis C coinfection
3% / 9%
4% / 7%
Discontinuation by W48
43 (22.9%)
56 (29.8%)
18 (9.3%)
For adverse event
N = 20
N = 27
N = 5
For lack of efficacy
N = 11
N = 21
N = 3
Lost to follow-up
N = 6
N = 2
N = 4
Other reasons
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 3

4. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Response to treatment at week 48 25 50
100 75 67 65
Adjusted difference
(95% CI) = 1.9%
(-5.9% ; 9.8%) 70 74
(95% CI) = - 2.9%
(-10.4% ; 4.5%)
ITT, NC=F
ITT, TLOVR
NVP (QD + BID) + TDF/FTC
ATV/r + TDF/FTC
HIV RNA < 50 c/mL
Primary analysis
(W24, W36 and W48) %
Treatment response similar for NVP BID (66.5%) and QD (67%)
ITT, snapshot : response rate
NVP : 67.3%
ATV/r : 78.8%
difference – 11.1% (95%CI : ; ; P = 0.003)
Mean CD4/mm3 increase at W48 :
+ 170 for NVP
+ 186 for ATV/r
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 4

5. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Adverse events through week 48
NVP QD
N = 188
NVP BID
ATV/r
N = 193
Adverse event, any
85.9%
86.5%
Drug-related adverse event
34.6%
48.7%
Discontinuation for adverse event
13.6%
3.6%
Serious adverse event
9.6%
8.8%
Rash
Any grade
14.9%
17.0%
12.4%
Grade 3
1.6%
Leading to discontinuation
3.7%
6.4%
Hepatitis
2.1%
Grade 3-4
1.0%
The majority of rash in NVP groups occurred during the lead-in phase
No Grade 4 rashes
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 5

6. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Grade 3 and 4 adverse events and liver enzyme increases
Combined NVP
N = 376
ATV/r
N = 193
Drug-related Grade 3-4 AE in > 1% in either group, any
Overall
9.0%
13.5%
Increased bilirubin
0.3%
6.2%
Increased ALT
1.3%
0.5%
Jaundice
3.1%
Hyperbilirubinemia
2.6%
Rash
1.6%
Hypertriglyceridemia
1.0%
Grade 3-4 liver related laboratory abnormalities
Grade 3 / Grade 4 ALT
3.7% / 3.5%
1.6% / 0
Grade 3 / Grade 4 AST
4.0% / 2.1%
2.1% / 0.5%
Grade 3/ Grade 4 total bilirubin
1.6% / 1.6%
44.6% / 8.8%
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 6

7. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Mean lipid values at baseline, W48 (LOCF) and change from baseline (LOCF)
Baseline
W48
Change to W48 p*
Combined NVP (N = 376)
ATV/r (N = 193)
ATV/r (N = 193)
Combined NVP vs ATV/r
TC (mg/dL)
155.68
153.84
180.05
173.46
24.37
19.62
0.0382
TG (mg/dL)
131.61
132.46
131.63
160.26
0.02
27.80
0.0001
HDL-c (mg/dL)
38.79
39.00
48.45
42.89
9.66
3.89
<
LDL-c (mg/dL)
91.57
88.83
106.32
99.26
14.98
10.43
0.0110
TC/HDL-c ratio
4.25
4.15
4.01
4.28
-0.24
0.13
ApoA1 (gL)
1.15
1.33
1.23
0.18
0.08
ApoB (g/L)
0.76
0.77 -
ApoB/A1 ratio
0.68
0.61
0.64
-0.07
-0.03
0.0080
* ANCOVA controlling for screeening viral load and CD4 cell count
ARTEN
Podzamczer D. HIV Medicine 2011;12:374-82

8. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Safety
Incidence of discontinuation due to adverse event: 13.6% NVP vs 3.6% ATV/r
Rash: 16% NVP vs 12.4% ATV/r (discontinuation due to rash : 5.1% vs 0%)
Hepatitis: 1.9% NVP vs 0% ATV/r
Grade 3-4 liver enzyme elevations: 4% NVP vs 1.5% ATV/r
Grade 3-4 hyperbilirubinemia: 3.2% NVP vs 54.4% ATV/r
No cases of Stevens-Johnson, toxic epidermal necrolysis, or death due to liver or skin toxicity
Mean change in lipid parameters (mg/dL) at week 48 (LOCF)
P = 0.011
Triglycerides
HDL-C
P = 0.041
p <
P <
- 5 5 10 15 20 25 30
28.1
10.5
19.6
9.7
15.0
24.3
-0.2
LDL-C
Total cholesterol
3.9
NVP
ATV/r
P =
-0.25
-0.2
-0.1
0.1
0.13
-0.24
0.2
Mean change in TC: HDL ratio at week 48 (LOCF)
ARTEN
Soriano V, Antivir Ther. 2011;16(3):339-48 8

9. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Resistance data
Virologic failure : 2 consecutive HIV RNA > 50 copies/mL at least 2 weeks apart
NVP QD
N = 188
NVP BID
ATV/r
N = 193
Virologic failure
N = 20
N = 24
N = 28
NNRTI resistance mutations
Y181C/I/V/S
N = 9
N = 15 -
Other NNRTI mutations
N = 5
NRTI resistance mutations
N = 2
M184V/I
N = 10
K65R
N = 4
N = 8
Protease resistance mutations
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 9

10. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
ARV-trial.com
ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC
Conclusion
NVP demonstrated at week 48 non-inferior antiviral efficacy compared with ATV/r when given along with TDF/FTC, despite more drug-related discontinuations with NVP than ATV/r
NVP BID and QD had similar efficacy and tolerability
The application of the recommended CD4+ T-cell thresholds when initiating first-line NVP therapy probably explain relative low rate of liver enzymes increases and discontinuations for liver toxicity
NVP was associated with a lower atherogenic lipid profile than ATV/r
At virologic failure, there was a high rate of resistance mutations selected by NVP and none with ATV/r
ARTEN
Soriano V. Antiviral Therapy 2011;16:339-48 10