C Orkin, 1 G Moyle, 2 M Fisher, 3 H Wang, 4 J Ewan 4 and ROCKET I Study Group. Chelsea and Westminster Hospital, London, UK;

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1 Switching from Kivexa [KVX] (ABC/3TC) + Efavirenz [EFV] to [ATR] (EFV/FTC/TDF) Reduces Cholesterol in Hypercholesterolaemic Subjects: Primary Endpoint Results of a 24- Week Randomised Study C Orkin, 1 G Moyle, 2 M Fisher, 3 H Wang, 4 J Ewan 4 and ROCKET I Study Group 1 Barts and The London NHS Trust, London, UK; 2 Chelsea and Westminster Hospital, London, UK; 3 Brighton and Sussex University Hospitals, UK; 4 Gilead Sciences Ltd, Cambridge, UK Second Joint Conference of the British HIV Association (BHIVA) with the British Association for Sexual Health and HIV (BASHH) April 2-23, 21 Manchester, UK Abstract No UK Sites Newcastle Central Middlesex Royal Free North Middlesex Homerton Edinburgh Belfast Bolton Heartlands North Manchester Leicester Whittle street C & W Barts St. Georges Gloucester Brighton

2 Background Dyslipidaemia contributes to CV risk 1 in HIV infection Higher Triglyceride levels are independently associated with an increased risk of MI in HIV-infected people 2 Comparative studies suggest tenofovir DF-based regimens have a favourable lipid profile relative to abacavir-based regimens 3 We sought to investigate if these changes are seen in hypercholesterolaemic subjects when switched from Kivexa + Efavirenz to a single tablet regimen (STR) of 1. Grover, SA, et al., Am J Cardiol 25; 95 (5): Worm, S, et al., CROI 21, Paper # Moyle, G et al., AIDS 26; 2 (16): RAVE Study Lipid Effects of Switching Thymidine Analogues to ABC or TDF Switch to TDF associated with improved lipid parameters Mean Change From BL at Week 48 (mg/dl (mmol/l)) * P =.3* 8.1 (.21) P =.4 * P =.34 * 3.5 (.9) P =.12.4 (.1) 6.2 (.7) -4.2 (-.11) -9.7 (-.25) (-.33) (-.45) TC LDL HDL TG * P values for between arm differences Moyle GJ, et al. AIDS. 26;2: Switch to TDF Switch to ABC

3 SWEET study Lipid Effects of Switching AZT to TDF Switch to TDF associated with improved lipid parameters Median Change From BL at Week 24 (mmol/l) N c Total Cholesterol p* =.8 b LDL-c p* =.45 HDL-c p* =.82 FTC/TDF AZT/3TC c Triglyceridese p* <.1 * TVD vs CBV comparison p-value from Wilcoxon Rank Sum test s a. Treated Analysis Set, Fasted b. p <.2 c. p <.1. from Wilcoxon sign rank test orf significant change from baseline Fisher et al., JAIDS 29; 51 (5): Objectives Primary objective: Determine whether switching from Kivexa + EFV to QD leads to a reduction in total fasting cholesterol at 12 weeks The secondary objectives: Evaluation of fasting metabolic parameters (e.g., LDL *, HDL, triglycerides, non-hdl cholesterol and cholesterol ratios) Evaluation of efficacy and safety Evaluation of changes in the 1-year risk for coronary heart disease outcomes as measured by Framingham risk score * LDL measured directly

4 ROCKET: Randomised Open Label Switch for Cholesterol on Kivexa Evaluation Trial* Stable Kivexa (ABC/3TC) + EFV 6 months (N=159) randomised 1:1 (TDF/FTC/EFV) KVX (ABC/3TC) + EFV Week 12 primary endpoint (TDF/FTC/EVF) (TDF/FTC/EVF) Week 24 Confirmation of Week 12 Undetectable viral load ( 5 copies/ml) 12 weeks Total cholesterol 5.2 mmol/l Adequate Baseline renal (CrCl 6mL/min and Hepatic (AST / ALT 5 x ULN) function 157 / 159 subjects enrolled received at least one dose of study drug * Presentation of data up to Week 12 Baseline Characteristics a Kivexa + Efavirenz Number of subjects Median age in yrs (IQR) 42 (36, 48) 44 (4, 5) Race White Black Asian Other 45 (57.%) 29 (36.7%) 2 (2.5%) 3 (3.8%) 48 (61.5%) 27 (34.6%) 3 (3.9%) Gender Male 61 (77.2%) 64 (82.1%) HIV RNA b < 5 copies/ml < 4 copies/ml 76/79 (96.2%) 79/79 (1%) 71/77 (92.2%) 77/77 (1%) Median BMI (kg/m 2 ) (IQR) 25.7 (23.5, 29.3) 25.8 (23.7, 28.) Median Fasting Total Cholesterol ( IQR) 6.62 (5.97, 7.26) 6.19 (5.8, 6.78) Number of Subjects on Prior Lipid Modifying Agents a. Treated Analysis Set b. One subject in Kivexa arm did not have a baseline viral load sample 9 (11.4%) 13 (16.7%)

5 Subject Disposition at Week 12 a N (%) (N=79) Kivexa + Efavirenz (N=78) Subjects completing 12 weeks of study 78 (98.7%) 74 (94.9%) Treatment Discontinuation (Prior to Week 12) 1 (1.3 %) 4 (5.1%) Adverse Events b 1 (1.3%) 1 (1.3%) Pregnancy Protocol Violation 2 (2.5%) Withdrew Consent Investigator s Decision 1 (1.3%) a. Treated AnalysisSet b. Adverse Events leading to study drug discontinuation: ATR arm - anxiety / heartburn / night sweats / general body pain/ palpitations KVX arm - depression Fasting Metabolic Parameters: Week 12 - Change from Baseline MITT Analysis Set (LOCF) Excluding subjects who started / modified lipid lowering medications during the study Median Change from Baseline (mmol/l) N=76 N=74 N=76 N= N=75 N= N=76 N=74 N=75 N= p <.1* p <.1* p <.1* p <.1* p=.3* LDL Cholesterol Total Cholesterol HDL Cholesterol Triglycerides TC: HDL ratio Kivexa + Efavirenz * P values for between arm differences Median value at baseline (mmol/l) LDL measured directly

6 Coronary Heart Disease Risk by Framingham Risk Score: Week 12 Median (IQR) Change from Baseline Median (IQR) Kivexa + Efavirenz Baseline 8. (4., 13.) 8. (4., 13.) Week (3., 13.) Change from BL to Week 12 a. (-3.,.) 8. (4., 1.). (-1.,.) a. p=.37 for ATR vs KVX +EFV comparison Viral Suppression Change by Visit ITT Analysis Set (Missing = Excluded) % Subjects with HIV RNA < 5 c/ml CD4 count Week 12 Change from Baseline % % Kivexa + Efavirenz 92.2% 9.3% 2 1 time Baseline Week 4 Week 12 Median CD4 count (cells/m m 3) (IQR) p=.13* (-36, 77) time (-96, 49) Kivexa + Efavirenz Virological failure [Subjects with 2 consecutive post-baseline value 4 copies/ml]: ATR /79 (%), KVX+EFV /78 (%) Median value at baseline (cells/mm3) * p values for between arm differences

7 Renal Function Creatinine Clearance - Median (IQR) Cockroft Gault (ml/min) and MDRD (ml/min/1.73m 2 ) 15 Creatinine Clearance: Cockroft Gault (ml/min) - Median (IQR) 15 Estimated GFR: MDRD (ml/min/1.732 m2) - Median (IQR) ml/min ATR ml/min/1.73 m ATR 25 KVX + EFV Normal boundary 25 KVX + EFV Normal boundary 4 Weeks Weeks No subject experienced a grade 3 or 4 renal abnormality in either arm Conclusions Switching from Kivexa + Efavirenz to in subjects with hypercholesterolaemia: Significantly reduces lipid parameters Maintains virological control Switching from Kivexa + Efavirenz to is beneficial in suitable hypercholesterolaemic patients

8 Acknowledgements 4 The ROCKET I Study Group Greater London: J Ainsworth, A Waters (North Middlesex, London) J Anderson, L Morumba (Homerton University, London) G Brook, M Chikohora (Central Middlesex, London) P Hay, A Adebiyi, M Cockerill, M Ndoro (St. Georges, London) M Johnson, A Carroll, F Turner (Royal Free, London) G Moyle, C Fletcher, J Osorio (Chelsea & Westminster, London) C Orkin, J Hand, C Desouza (Barts & Royal London) South East England: M Fisher, N Perry, T Maher, A Bray (Brighton & Sussex University) South West England: A de Burgh Thomas, M Bunting, L Jones (Gloucester Royal) Midlands: North England: Scotland: Northern Ireland: D White, J Groves (Birmingham Heartlands) J Ross, L Brown, K Hood (Selly Oak, Birmingham) J Dhar, S Johnson (Leicester Royal Infirmary) E Morgan, R Hewart (Royal Bolton) E Ong, J Wotherspoon (Newcastle General) E Wilkins, E Stockwell, A Robertson (North Manchester General) C Leen, S Morris, L Ellis (Western General, Edinburgh) R Maw, S McKernan (Royal Victoria, Belfast) C Herath, J Ewan, M (Hui) Wang, R Ebrahimi (Gilead Sciences Limited, Cambridge) We wish to thank all the patients that participated in the study.