1. Switch to TDF/FTC/RPV - SPIRIT Study

2. SPIRIT study: switch PI/r + 2 NRTI to TDF/FTC/RPV STR  Design TDF/FTC/RPV STR 24 weeks 48 weeks Primary Endpoint Secondary Endpoint N = 317 N = 159 PI/r +2 NRTIs 476 HIV+ adults Stable PI + RTV + 2 NRTI ≥ 6 months with HIV RNA < 50 c/mL On 1 st or 2 nd regimen No prior NNRTI use No known resistance to study agents TDF/FTC/RPV STR Randomisation 2 : 1 Open-label 24 weeks Primary Endpoint 48 weeks Secondary Endpoint  Objective –Primary Endpoint : Non-inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W24 (FDA snapshot analysis) ; upper limit of the 95% CI for the difference = 12% –Secondary Endpoints: Proportion of HIV1 RNA < 50 copies/mL at W48 ; Change in fasting lipid and CD4 cell count at W24 and W48 ; Safety and tolerability SPIRIT Fisher M, HIV11, Glasgow 2012, Abs. P285

3. Baseline characteristics 2 NRTI + PI/rTDF/FTC/RPV Female9%14% Baseline CD4/mm 3 (mean)600576 Time since first ART, years (median)2.62.9 NRTI TDF/FTC81% ABC/3TC13% ZDV/3TC3.4% PI/r ATV/r37% DRV/r20% FPV/r33% LPV/r8% ART at screening SPIRIT Fisher M, HIV11, Glasgow 2012, Abs. P285 SPIRIT study: switch PI/r + 2 NRTI to TDF/FTC/RPV STR

4. Palella F, IAC 2012, Abs. TUAB0104 ; Fisher M, HIV11, Glasgow 2012, Abs. P285 HIV RNA < 50 c/mL at W24 (ITT, snapshot) HIV RNA < 50 c/mL, ITT, M = Excluded RPV = 99.7 % vs PI/r = 94.7 % Non inferiority 93.7 89.9 difference (95% CI) TDF/FTC/RPV - PI/r 3.8 (- 1.6 ; 9.1) : non inferiority 0 20 40 60 80 100 % 92.1 100 difference (95% CI) : 3.2 (- 4.8 ; 11.3) difference (95% CI) : 5.8 (- 1.4 ; 12.9) 95 95.5 89.2 92.3 0 20 40 60 80 HIV RNA, pre-ART (23 patients TDF/FTC/RPV and 14 PI/r excluded from analysis (data not avalaible)) > 100 000 c/ml < 100 000 c/ml 152/ 160 83/ 93 48/ 52 128/ 134 % SPIRIT TDF/FTC/RPV (delayed switch, W24 to W48) 2 NRTI + PI/rTDF/FTC/RPV Virologic failure 0.9 5 1.3 3/3178/1592/152 % SPIRIT study: switch PI/r + 2 NRTI to TDF/FTC/RPV STR

5.  Among the 24 patients with the K103N mutation on historical genotype –22 achieve HIV RNA < 50 c/mL at W48 –1 virologic failure (pre-existing mutations : K103N + V179I, emergence : M184V, E138K and V108V/I) –1 without data at W48 (HIV RNA < 50 c/mL at last study visit)  Virologic failure on TDF/FTC/RPV, n = 7 (1.5%) –3 without emergence of resistance mutations –4 with emergence of resistance mutations K103N + L100I + M184I M184I E138E/K + M184M/V E138K + V108V/I + M184V White K, IWHHDR 2012, Abs. 49 ; Palella F, IAC 2012, Abs. TUAB0104 ; Fisher, HIV11, Glasgow 2012, Abs. P285 SPIRIT SPIRIT study: switch PI/r + 2 NRTI to TDF/FTC/RPV STR

6. Palella F, IAC 2012, Abs. TUAB0104 ; Fisher, HIV11, Glasgow 2012, Abs. P285 Mean change from baseline at W24 RPV Immediate switch (at W48) PI/r (at W24) RPV Delayed switch at W24 Adverse events5.7 %6.9 %7.9% Laboratory abnormalities 8.8 %11.3 %15.2% Discontinuation for adverse event (W24) –TDF/FTC/RPV, n = 6 tubulopathy, n = 1 neuro-psychiatric events, n = 4 (depression, headache, insomnia, psychiatric event) –2 NRTI + PI/r, n = 0 GFR decrease significantly more important with RPV -60 -50 -40 -30 -20 -10 0 10 - 25 - 1 -16 0 - 53 3 - 4 - 1 - 0.27 0.08 p < 0.001 for all comparisons 2 NRTI + PI/r Chol-tot (mg/dl) LDL-c (mg/dl) TG (mg/dl) HDL-c (mg/dl) Rapport TC : HDL TDF/FTC/RPV SPIRIT Grade 3-4 Adverse events and laboratoratory abnormalities to W48 SPIRIT study: switch PI/r + 2 NRTI to TDF/FTC/RPV STR