1. NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A4001078 VEMAN
ARV-trial.com
NRTI-sparing
SPARTAN
PROGRESS
RADAR
NEAT001/ANRS 143 A
VEMAN
MODERN 1

2. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Design
Randomisation
1 : 1
Open-label
W48
W96
> 18 years
ARV-naïve
HIV RNA > 1,000 c/mL
Any CD4 cell count
HBs Ag negative
No R to LPV, TDF or FTC
N = 101
LPV/r 400/100 mg + RAL 400 mg BID
N = 105
LPV/r 400/100 mg BID + TDF/FTC QD
Objective
Non inferiority of LPV/r + RAL at W48: % HIV RNA < 40 c/mL by intention to treat, TLOVR analysis (lower limit of the 95% CI for the difference = -20%, 90% power)
PROGRESS
Reynes J.HIV Clin Trials 2011;12:255-67 2

3. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Baseline characteristics and patient disposition
LPV/r + RAL
N = 101
LPV/r + TDF/FTC
N = 105
Mean age, years 40 39
Female
13%
18%
HIV RNA (log10 c/mL), mean
4.24
4.25
HIV RNA >100,000 c/mL
15%
CD4 cell count (/mm3), mean
289
298
CD4 < 200 per mm3
24%
29%
Discontinuation by W48
8 (7.9%)
11 (10.5%)
For virologic failure
N = 1
N = 2
For adverse event
Lost to follow-up
N = 3
Non-compliance
Withdrew consent
Pregnancy
Discontinuation by W96
19 (18.8%)
15 (14.3%)
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 3

4. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Response to treatment
HIV RNA < 40 c/mL 25 50
100 75
83.2
84.8 %
Difference
(95% CI)=
- 1.6% (- 12 ; 8.8)
66.3
68.6
LPV/r + RAL
LPV/r + TDF/FTC
ITT, TLOVR
84.5
93.8
Observed
88.9
85.2
W48
W96
- 9.2% ( ; - 0.3)
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 4

5. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Protocol-defined criteria for genotype testing
At or after W8, in patients having achieved HIV-1 RNA < 40 c/mL, HIV-1 RNA ≥ 40 c/mL with confirmatory sample > 400 c/mL
HIV-1 RNA increase > 0.5 log10 c/mL above study nadir and > 400 c/mL on 2 consecutive measurements
Failure to achieve HIV-1 RNA < 400 c/mL at by week 24
Resistance data
LPV/r + RAL
LPV/r + TDF/FTC
Virologic failure, N 8 5
At W48 / Between W48 and W96
4 / 4
3 / 2
Presence of resistance mutations, N 3 1
W0-W48 failures
INSTI resistance mutations
M184V
Protease resistance mutations
2 (N155H + G163R, N155H + T97A) -
W48-W96 failures
1 (G140S + Q148H)
1 (V32I, M46I, I47V)
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 5

6. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Adverse events (during the 96 weeks)
LPV/r + RAL
LPV/r + TDF/FTC P
Discontinuation for AE
5 (5.0 %)
4 (3.8 %)
AE ≥ 2% in either group
Diarrhoea
7.9 %
16.2 %
0.088
Asthenia
2.9 %
Dyspepsia
Grade 3 or 4 laboratory abnormalities
CK > 10 x ULN
9.9 %
< 0.05
Total cholesterol > 7.77 mmol/L
16.8%
13.5 %
Triglycerides > mmol/L
4.8 %
Lipase > 2 x ULN
4.0 %
7.7 %
ALT > 5 x ULN / AST > 5 x ULN
5.0 % / 5.0 %
2.9 % / 2.9 %
eGFR< 50 mL/min
1.0 %
3.8 %
eGFR (mL/min) mean reduction at W96 from baseline : (TDF/FTC) vs (RAL), P = 0.035
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 6

7. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Total bone mineral density, g/cm2 (DXA)
* Within group, P<0.05
† Between group, P<0.05
LPV/r + RAL
LPV/r + TDF/FTC 48 96
Weeks
+0.68%
-2.48%
P<0.001 -4 1 -1 -2 -3
Mean Percent Change
From Baseline † * -5
The analysis that I’m going to present uses data from the PROGRESS study, which were presented at this meeting 2 years ago in Rome and subsequently published. In this study, ART-naïve subjects randomized to LPV/r + TDF/FTC had greater loss in BMD compared to those randomized to LPV/r+ RAL . It’s interesting to note that this is one of the only studies in the literature looking at bone with ART initiation that has not shown a decrease in BMD in one of its arms.
Subjects taking LPV/r + RAL through 96 weeks had statistically significantly larger mean percent increases in fat in the arms and legs, but not in the trunk, compared with subjects taking LPV/r + TDF/FTC
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 7

8. PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
ARV-trial.com
PROGRESS Study: LPV/r + RAL vs LPV/r + TDF/FTC
Summary
Through 96 weeks, LPV/r + RAL demonstrated similar efficacy, safety and tolerability than the traditional triple combination of LPV/r + TDF/FTC
Emergence of resistance mutations infrequent
Lipid changes more favourable with LPV/r + TDF/FTC
Decrease of eGFR more pronounced with LPV/r + TDF/FTC
No change in bone mineral density with LPV/r + RAL
Limitations
Sample size
Low proportion of patients with baseline HIV-1 RNA > 100,000 c/mL
PROGRESS
Reynes J.HIV Clin Trials 2011;12: ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 8