Switch NNRTI to NNRTI  Switch EFV to ETR –CNS toxicity study –Patient’s preference study

Switch EFV to ETR: Patient’s preference ETR 400 mg QD + EFV placebo + 2 NRTI 24 weeks 48 weeks Primary Endpoint Secondary Endpoint N = 28 N = 30 EFV 600 mg QD + ETR placebo + 2 NRTI  Design Randomisation 1: 1 Double blind Crossover 12 weeks Primary Endpoint  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 SWITCH EFV/ETR 58 HIV+ adults Stable EFV + 2 NRTI No EFV-related CNS symptoms HIV RNA 3 months Nguyen A. AIDS 2011;25:57-63 W6W12 EFV 600 mg QD + ETR placebo + 2 NRTI ETR 400 mg QD + EFV placebo + 2 NRTI

Baseline characteristics and disposition  Median duration of EFV exposure: 3.9 years (IQR : ) EFV first N = 30 ETR first N = 28 Median age, years47 Female13%11% CDC category C30%25% HIV RNA copies/mL, median40 CD4/mm 3, median On TDF + FTC / ABC + 3TC47% / 30%50% / 39% EFV plasma concentration (ng/mL), median2022 (1558 – 2648)2112 ( ) Withdrawal12 SWITCH EFV/ETR Nguyen A. AIDS 2011;25:57-63 Switch EFV to ETR: Patient’s preference

Patient’s preference and drug prescription at W12, N * p < (15/21 : 71% vs 16/17 : 91%) SWITCH EFV/ETR EFV first N = 28 ETR first N = 27 Patient’s preference* Prefer EFV151 Prefer ETR616 No preference710 Prescription at W12 EFV2312 ETR515 SWITCH EFV/ETR Nguyen A. AIDS 2011;25:57-63 Switch EFV to ETR: Patient’s preference

 Anxiety, depression and sleep assessment –No significant differences among depression, anxiety, sleepiness or sleep quality between the two study periods  Safety and laboratory parameters –Serious adverse events, N = 2, unrelated to study drugs –Significantly lower lipid levels in patients on ETR when compared with patients on EFV Total cholesterol (median change : mmol/l; IQR : - 1.1, - 0.2; p < ) LDL-cholesterol (median change : mmol/l; IQR : - 0.7, - 0.1; p < ) Triglycerides (median change : mmol/l; IQR : - 0.9, - 0.1; p = )  In conclusion, –Patients on long-term EFV do not, as a rule, prefer ETR after a switch –In patients who have tolerated an EFV regimen for extended periods, switching to an ETR regimen is of limited benefit insofar, as neuropsychiatric side-effects are a concern –Patients on ETR, however, had a better lipid profile Switch EFV to ETR: Patient’s preference SWITCH EFV/ETR Nguyen A. AIDS 2011;25:57-63