1. The impact of switching to etravirine on efavirenz-related CNS toxicity. Laura Waters 1, Martin Fisher 2, Alan Winston 3, Chris Higgs 1, Wendy Hadley 2, Lucy Garvey 3, Sundhiya Mandalia 1, Nicky Perry 2, Nicola Mackie 3 & Mark Nelson 1. 1) Chelsea & Westminster Hospital, London; 2) Royal Sussex County Hospital, Brighton; 3) St Mary’s Hospital, London 2 NRTI + ETR 400mg OD + EFV-placebo 2 NRTI + EFV 600mg OD + ETR-placebo 2 NRTI + EFV (at least 12 weeks) 2 NRTI + ETR 400mg OD 2 NRTI + ETR 400mg OD Blinded Phase: Baseline to Week 12 Open-label Phase: Week 12 to Week 24 1:1 randomisation 38 males, 37 Caucasian, median age 43 years Median prior EFV exposure 21.4 months Baseline NRTI: TDF/FTC 58%, ABC/3TC 29%, other 13% Median baseline CD4 468; 100% HIV-RNA <50 copies/ml 20 randomised to immediate switch (IS) 18 to delayed switch (DS) Baseline CNS AE similar: 90% IS and 88.9% DS at least 1 G2-4 CNS AE More insomnia in IS arm 74% vs 39% (p=0.024) 1 LFU in IS arm, 2 LFU and 1 SAE in DS arm

2. 12 CNS AE considered according to ACTG DAIDS Grading Baseline to week 12 results (Blinded Phase): –IS: G2-4 overall CNS AE (90% to 60%; p=0.041), abnormal dreams (50% to 20%; p=0.041) –DS: No significant changes Week 12 to week 24 results (open-label phase): –IS: No further changes –DS: G2-4 abnormal dreams (67% to 20%; p=0.023), median G2-4 CNS AE (3 to 1; p=0.003) 0 1 2 3 4 5 6 ISDS Baseline 12 Weeks 16 Baseline 12 Weeks 0 2 4 6 8 10 12 14 ISDS P=0.001 P=0.192 P=0.003 P=0.508 Median Number G2-4 CNS AE CNS Score

3. Viral suppression: All subjects maintained HIV-RNA <50 copies/ml CD4: During blinded phase, +40 and +6 in IS and DS arms, respectively; in combined analysis after 12 weeks ETR +43 (p=0.027 vs baseline) Safety: 1 SAE; one G3 flatulence on ETR; no other G3/4 AE; no rash or hepatotoxicity Lipid changes after 12 weeks ETR (ie combined baseline to week 12 in IS arm and week 12 to week 24 DS arm): Conclusions: –Switching from EFV to ETR improved overall G2-4 CNS AE, median no. G2-4 CNS AE, CNS score and, specifically, abnormal dreams and insomnia –Switching from EFV to ETR also yielded significant improvements in fasting TC and LDL-C –There were no cases of rash or hepatotoxicity –Virological and immunological efficacy were maintained. Lipid parameterChange in mmol/l (SD)P-value Total cholesterol-0.64 (1.02)<0.001 HDL-cholesterol-0.04 (0.21)ns LDL-cholesterol-0.58 (1.09)0.021 Triglycerides-0.19 (0.62)0.092