1. Switch to RAL-containing regimen  Canadian Study  CHEER  Montreal Study  EASIER  SWITCHMRK  SPIRAL  Switch ER

2. Switch-ER Study: Switch EFV to RAL RAL 400 mg BID + EFV placebo + 2 NRTI 24 weeks 48 weeks Primary Endpoint Secondary Endpoint N = 29 N = 24 EFV 600 mg QD + RAL placebo + 2 NRTI  Design Randomisation 1: 1 Double blind Crossover  Objective Primary Endpoint: patient preference of first or second regimen, by questionnaire at W12 Standardized questionnaires: patient anxiety and depression, sleepiness during the day, sleep quality and antiretroviral satisfaction (HIVTSQc) Plasma drug concentration: D1 and end of both treatment phases 57 HIV+ adults Stable EFV + 2 NRTI No EFV-related CNS symptoms HIV RNA 3 months Nguyen A. AIDS 2011;25:1481-7 W2W4 EFV 600 mg QD + RAL placebo + 2 NRTI RAL 400 mg BID + EFV placebo + 2 NRTI SWITCH-ER

3. Baseline characteristics and outcome SWITCH-ER EFV first N = 24 RAL first N = 29 Median age, years4748 Duration of HIV infection, median years13.28.8 HIV RNA < 50 copies/mL100% CD4/mm 3, median 597637 Duration on EFV therapy, median (IQR)3.4 (1.8 – 7.6) Background NRTI : TDF + FTC / ABC + 3TC 37.5% / 54.2%69% / 27.6% EFV plasma concentration (ng/mL), median (IQR) 1894 (1378 – 2438) 2182 (1522 – 2616) Withdrawal4 Patient’s preference at W4 Prefer EFV75 Prefer RAL913 No preference811 Nguyen A. AIDS 2011;25:1481-7 Switch-ER Study: Switch EFV to RAL

4.  HIVTSQc questionnaire (Treatment satisfaction) –Patients in the RAL-group were more satisfied by RAL than by EFV (p = 0.002)  Anxiety, depression and sleep assessment –No significant differences in depression or sleep quality between groups –Significant less anxiety and stress score with RAL (p = 0.04 and 0.03, respectively)  Safety and laboratory parameters –Serious adverse events, N = 1, unrelated to study drugs –Significantly lower lipid levels in patients on RAL when compared with patients on EFV Total cholesterol (median change : - 0.4 mmol/l; IQR : 0.9, - 0.1; p < 0.0001) LDL-cholesterol (median change : - 0.2 mmol/l; IQR : 0.6, - 0.2; p = 0.004) HDL-cholesterol (median change : - 0.1 mmol/l; IQR : 0.2, 0; p = 0.005) Triglycerides (median change : - 0.2 mmol/l; IQR : 0.6, 0.1; p = 0.036) HDL:Total cholesterol ratio (median change : - 0.1; IQR : 0.4, 0.3; p = 1)  No loss of virological suppression over 3 months follow-up SWITCH-ER Switch-ER Study: Switch EFV to RAL Nguyen A. AIDS 2011;25:1481-7

5.  Summary –Half of patients previously on a stable EFV preferred to switch to RAL, after double-blind exposure to RAL for 2 weeks –Substitution of EFV by RAL significantly impacted on lipid levels, stress, and anxiety scores –After study completion, 51% of patients switched to RAL –Study limitations Small sample size Few women Exclusion of patients not tolerating EFV SWITCH-ER Switch-ER Study: Switch EFV to RAL Nguyen A. AIDS 2011;25:1481-7