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

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

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;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 3

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% (- 18.9 ; - 0.3) PROGRESS Reynes J.HIV Clin Trials 2011;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 4

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;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 5

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 > 8.475 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 : - 7.33 (TDF/FTC) vs - 1.43 (RAL), P = 0.035 PROGRESS Reynes J.HIV Clin Trials 2011;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 6

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;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 7

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;12:255-67 ; Reynes J. AIDS Res Hum Retroviruses 2013;29:256-65 8