1. Switch PI/R to ETR  Etraswitch

2. Etraswitch Study: Switch PI/r to ETR Continuation of current PI/R + 2 NRTI N = 21 N = 22 ETR 400 mg QD* + 2 NRTI  Design Randomisation 1: 1 Open-label  Objective –Primary Endpoint: % HIV RNA < 50 c/mL, on-treatment and ITT, M=F –Secondary endpoints: change in CD4, CD8, metabolic parameters (lipids and glucose), safety, patient satisfaction ETRASWITCH 43 HIV+ adults Stable PI/r + 2 NRTI ≥ 12 months HIV RNA 6 months No resistance to NRTI or NNRTI, or prior virologic failure At least 1 one of the following : LDL-c > 130 mg/dl, triglycerides > 150 mg/dl, on lipid-lowering agent, ARV-related gastro-intestinal disturbances, dissatisfaction with current regimen Echeverria P. PLOS One 2014;9:e84676 W48 * 4 x 100 mg pills dissolved in water

3. Baseline characteristics and disposition * Frequency of individual events similar in both groups except for insomnia (75% vs 39%, P = 0.024) PI/r group N = 21 ETR group N = 22 Median age, years4647 Female24%36% Time on ART, median years8,18,3 Time on PI, median years5,23,6 Reason for change Dyslipidemia43%55% Gastro-intestinal disturbances10%14% Posology (BID)/RTV48%32% Use of lipid-lowering agent10%18% NRTI : TDF/FTC ; ABC/3TC62% ; 33%59% ; 36% Baseline PI/r : ATV / LPV / FPV / SQV57 % / 19 % / 14% / 10%51% / 32% / 14% / 5% Discontinuation by W48 1 (wish to simplify) 2 (diarrhea, withdrawal) ETRASWITCH Echeverria P. PLOS One 2014;9:e84676 Etraswitch Study: Switch PI/r to ETR

4. Virologic and immunologic outcomes at W48 PI/r + 2 NRTIsETR + 2 NRTIs 0 25 50 100 75 100 90.9 20 % 95.2 202122 100 On-TreatmentITT, M = F N=  No difference in CD4 change HIV RNA < 50 c/ml ETRASWITCH Echeverria P. PLOS One 2014;9:e84676 Etraswitch Study: Switch PI/r to ETR

5. Metabolic parameters and satisfaction PI/r groupETR group Baseline N = 21 W48 N = 20 p Baseline N = 22 W48 N = 20 p Total cholesterol, mg/dl197.8199ns207.2190.8< 0.001 HDL-cholesterol, mg/dl54.255.1ns52.952.8ns HDL:Total cholesterol ratio3.863.78ns3.963.57ns LDL-cholesterol, mg/dl114.6113.6ns116.6110.5ns Triglycerides, mg/dl145.7116.1ns186.4132.4< 0.001 Glycemia, mg/dl90.388.0ns97.492.70.03 Satisfaction65.3ns7.79.2< 0.01  Safety No Grade3-4 clinical adverse events No significant changes in liver enzymes in either group, no Grade 3-4 elevations ETRASWITCH Echeverria P. PLOS One 2014;9:e84676 Etraswitch Study: Switch PI/r to ETR

6.  Conclusion –Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly Etraswitch Study: Switch PI/r to ETR ETRASWITCH Echeverria P. PLOS One 2014;9:e84676