1. Switch EFV to ETR - Efavirenz to Etravirine

2. Efavirenz to Etravirine switch in patients with CNS adverse events Waters L, AIDS 2011;25:65-71 Design Endpoints –Primary: change in the proportion of patients experiencing grade 2-4 CNS toxicity at week 12 –Secondary: change in CNS score, median number of grade 2-4 CNS adverse events, viral suppression, CD4 change, fasting lipids, safety 2 NRTI + ETR 400 mg QD + EFV placebo 2 NRTI + EFV 600 mg QD + ETR placebo Randomisation 1 : 1 HIV+ adults On 2 NRTI + EFV 12 weeks HIV-1 RNA < 50 c/mL CD4 > 50/mm 3 Ongoing CNS symptoms N = 18 N = 20 2 NRTI + ETR 400 mg QD 2 NRTI + ETR 400 mg QD Blinded Phase W0-W12 Open-label Phase W12-W24

3. Baseline characteristics, 38 patients –Median age 43 years –Median duration of EFV: 21.4 months (range: 3.5 – 117.5) –Median CD4: 510/mm 3 –NRTI backbone: TDF/FTC = 61% ; ABC/3TC = 29% –Similar frequency of individual grade 2-4 CNS adverse events (AE) in immediate and delayed ETR switch arm, except for insomnia (p=0.024) Immediate ETRDelayed ETRP** W0W12pW0W12p Grade 2-4 CNS AE 90%60%0.04188.9%81.3%1- Abnormal dreams 50%20%0.04166.7%62.5%0.720.009 Insomnia 75%50%0.07438.9%43.8%1- Median number of grade 2-4 CNS AE 41.50.00333-- CNS score*, median 1460.001107.50.19- * Sum of total of all grades of CNS AE ; ** change in immediate vs delayed switch Grade 2-4 CNS AE: change from baseline to Week 12 Efavirenz to Etravirine switch in patients with CNS adverse events Waters L, AIDS 2011;25:65-71

4. Combined analysis, at W12 of ETR in both arms –Grade 2-4 CNS AE Significant reductions (baseline ; W12) in overall AE (89% ; 60% ; p=0.009), insomnia (63% ; 37% ; p=0.016), abnormal dreams (57% ; 20% ; p=0.001) and nervousness (29% ; 9% ; p=0.046) –Virologic and immunologic efficacy HIV-1 RNA < 50 c/mL at all visits, median CD4 rise : + 43/mm 3 –Fasting lipids Reductions in total cholesterol (- 0.64 mmol/L, p<0.001) and LDL-cholesterol (- 0.58 mmol/L, p=0.021) –No rash or hepatotoxicity Conclusion –Switching EFV to ETR led to a significant reduction in some but not all grade 2-4 CNS adverse events –Once-daily ETR is an efficacious, tolerable and lipid-friendly alternative to EFV in patients with persistent CNS toxicity Efavirenz to Etravirine switch in patients with CNS adverse events Waters L, AIDS 2011;25:65-71