1. ARTEMIS: Efficacy and safety of lopinavir (BID vs QD) and darunavir (QD) in antiretroviral-naïve patients N Clumeck, J Van Lunzen, P Chiliade, B Clotet, C Vanden Abeele, E Lefebvre, T Vangeneugden, R DeMasi, S Spinosa-Guzman

2. ARTEMIS: Phase III study design Multinational study, conducted across 26 countries DRV/r 800/100mg QD + TDF 300mg and FTC 200mg QD (N=343) LPV/r 400/100mg BID or 800/200mg QD + TDF 300mg and FTC 200mg QD (N=346) 689 ARV-naïve patients – VL>5,000 – no CD4 entry restrictions DeJesus E, et al. 47th ICAAC 2007. Abstract H-718b DRV/r = darunavir/ritonavir; TDF = tenofovir; FTC = emtricitabine; LPV/r = lopinavir/ritonavir

3. Primary end point –proportion of patients with an HIV RNA <50 copies/mL at Week 48 (ITT-TLOVR) Primary objective –demonstrate non-inferiority of DRV/r QD vs LPV/r (BID or QD) based on the primary endpoint Secondary objective –evaluate efficacy, safety and tolerability over 192 weeks ARTEMIS: study objectives DeJesus E, et al. 47th ICAAC 2007. Abstract H-718b

4. 62,100 (667–4,580,000) 218 (2–714) 48 (14) 34 (10) 70,800 (835–5,580,000) 228 (4–750) 43 (13) 26 (8) Baseline disease characteristics Median HIV-1 RNA, copies/mL (range) Median CD4, cells/mm 3 (range) HBV/HCV co-infected, n (%) CDC class C, n (%) 41% 36% 241 (70) 35 (9) 153 (44) LPV/r overall* (N=346) DRV/r QD (N=343) 40% 36% 239 (70) 36 (9) 137 (40) Stratification factors at screening CD4 count <200 cells/mm 3 Plasma HIV-1 RNA ≥100,000 copies/mL Baseline demographics Male, n (%) Mean age, years (SD) Caucasian, n (%) ARTEMIS: baseline characteristics *Includes all patients receiving LPV/r, regardless of BID or QD dosing schedule DeJesus E, et al. 47th ICAAC 2007. Abstract H-718b

5. Estimated difference in response vs LPV/r for non-inferiority: PP = 5.6% (95% CI –0.1;11.3) p<0.001 Estimated difference in response vs LPV/r for non-inferiority: Per-protocol = 5.6% (95% CI -0.1;11.3) p<0.001 Estimated difference in response vs LPV/r for superiority: ITT = 5.5% (95% CI -0.3;11.2) p=0.062 ARTEMIS primary endpoint: viral load <50 copies/mL at Week 48 (ITT-TLOVR) 50 40 30 20 10 0 100 90 80 70 60 84% 78% 481216243648 Time (weeks) Patients with viral load <50 copies/mL (% ± SE) LPV/r overall* (N=346) DRV/r QD (N=343) 2 *Includes all patients receiving LPV/r, regardless of BID or QD dosing schedule DeJesus E, et al. 47th ICAAC 2007. Abstract H-718b

6. Analysis background and rationale Previous findings in treatment-naïve patients suggest that the efficacy of LPV/r is similar between the QD and BID dosing regimens 1 Recent data from study ACTG 5073 showed LPV/r BID was more effective than LPV/r QD in treatment-naïve patients with high baseline viral loads (≥100,000 copies/mL) 2 The present analysis evaluated virological response rates for LPV/r QD and BID and DRV/r QD in treatment-naïve patients in the ARTEMIS trial 3 1. Gathe J, et al. 11th CROI 2004. Abstract 570 2. Mildvan D, et al. 14th CROI 2007. Abstract 138 3. DeJesus E, et al. 47th ICAAC 2007. Abstract H-718b

7. Objective of exploratory analysis Compare the efficacy and safety of DRV/r QD with LPV/r QD and BID –LPV/r dosing schedules were not randomised based on local regulatory approval* and investigator or patient preference *LPV/r QD is approved for treatment-naïve patients in the USA

8. BID/QD* BID QD 27 (8%)0 267 (77%)0 52 (15%)343 (100%) DRV/r (N=343) Use of QD and BID dosing in ARTEMIS Dosing LPV/r (N=346) * Excluded from the analysis

9. Baseline disease characteristics 228 (4–750) Median CD4, cells/mm 3 (range) 218 (2–714)228 (16–659) 70,800 (835–5,580,000) Median HIV-1 RNA, copies/mL (range) 61,800 (667–4,580,000) 58,850 (6,400–888,000) ARTEMIS: baseline characteristics 36% Plasma HIV-1 RNA ≥100,000 copies/mL 40% CD4 <200 cells/mm 3 Stratification factors at screening 137 (40) Caucasian, n (%) 36 (18–70) Mean age, y (range) 239 (70) Male, n (%) Baseline demographics DRV/r QD (N=343) 35% 41% 118 (45) 34 (19–63) 171 (64) LPV/r QD* (N=52) 35% 37% 43 (13) HBV/HCV co-infected, n (%) 39 (15)5 (10) 24 (46) 40 (20–68) 46 (88) LPV/r BID* (N=267) *27 patients receiving LPV/r BID and QD during the study were excluded from this analysis 26 (8) CDC class C, n (%) 24 (9)8 (15)

10. Week 48 response by QD and BID dosing (ITT-TLOVR) 346 N = 0 20 40 60 80 100 Patients with VL <50 copies/mL (%) 343 DRV/r QD 84 LPV/r overall 78 *Difference rounded † 27 patients receiving LPV/r BID and QD during the study were excluded from this analysis 267 LPV/r BID † 81 52 LPV/r QD † 71 Difference 9% * (95% CI -3; 21) Difference 13% (95% CI 1; 24; p<0.05) Difference 3% (95% CI -3; 9) † 27 patients receiving LPV/r BID and QD during the study were excluded from this analysis

11. N = 22617534226 86 79 85 Baseline viral load <100,000 copies/mL 0 20 40 60 80 100 Patients with VL <50 copies/mL (%) 86 N = 226175342261209218117 79* 67* 71 56* 0 20 40 60 80 100 Patients with VL <50 copies/mL (%) DRV/r QD LPV/r overall LPV/r BID † LPV/r QD † Baseline viral load ≥100,000 copies/mL *p<0.05 for DRV/r QD vs LPV/r overall and vs LPV/r QD Week 48 response by baseline viral load † 27 patients receiving LPV/r BID and QD during the study were excluded from this analysis DRV/r QD LPV/r overall LPV/r BID † LPV/r QD †

12. ARTEMIS: virological failure (VF) and emergence of mutations 1‡1‡ 1‡1‡ 1‡1‡ IAS-USA 1 NRTI RAMS 01†1† 0IAS-USA 1 PI RAMS 41110 Paired baseline and VF genotype available (n) 10 (19%)31 (12%)34 (10%)VF (>50 copies/mL) LPV/r QD* (N=52) LPV/r BID* (N=267) DRV/r QD (N=343) 1. Johnson VA, et al. Top HIV Med 2006;14:125–130 *27 patients receiving LPV/r BID and QD during the study were excluded from this analysis VF by TLOVR non-VF censored (at any time, regardless of reason for discontinuation) † A71T, V77I ‡ M184V or M184I/V 2‡2‡ 1†1† 18 49 (14%) LPV/r overall (N=346)

13. ARTEMIS: grade 2–4 AEs in ≥2% of patients (at least possibly related to study drug, excluding lab-related events) No renal SAEs and no treatment discontinuations due to renal AEs 1 (2)3 (1)Rash (all types) 0 (0)8 (3)Nausea 9 (17) † 22 (8) † Diarrhoea LPV/r BID* (N=267) Incidence, n (%) † p<0.05 for DRV/r QD vs all LPV/r groups 9 (3) 6 (2) 14 (4) † DRV/r QD (N=343) 4 (1) 10 (3) 34 (10) † LPV/r overall (N=346) LPV/r QD* (N=52) *27 patients receiving LPV/r BID and QD during the study were excluded from this analysis

14. ARTEMIS: grade 2–4 lipid abnormalities in ≥2% of patients 9 (17) ‡ 27 (10) ‡ Triglycerides 4 (8)31 (12) Low-density lipoprotein 8 (15)69 (26) † Total cholesterol LPV/r QD* (N=52) LPV/r BID* (N=267)Incidence, n (%) *27 patients receiving LPV/r BID and QD during the study were excluded from this analysis 38 (11) ‡ 36 (11) 78 (23) † 10 (3) ‡ 44 (13) 44 (13) † DRV/r QD (N=343) LPV/r overall (N=346) † p<0.05 for DRV/r QD vs LPV/r overall and vs LPV/r BID ‡ p<0.05 for DRV/r QD vs all LPV/r groups

15. ARTEMIS: conclusions At Week 48, 84% of DRV/r patients versus 78% of LPV/r patients achieved a viral load <50 copies/mL –DRV/r 800/100mg QD was non-inferior to LPV/r (QD or BID) in treatment-naïve patients in the ARTEMIS primary efficacy analysis DRV/r QD was superior to LPV/r (overall) in patients with baseline viral load ≥100,000 copies/mL In this non-randomised comparison of ARTEMIS, patients receiving DRV/r QD compared with those receiving LPV/r QD demonstrated significant differences in –virological response (<50 copies/mL) in patients with high viral load –incidence of treatment-related, moderate to severe diarrhoea –incidence of treatment-emergent, moderate to severe triglyceride elevations Once-daily DRV/r is safe and effective in treatment-naïve patients Studies evaluating once-daily DRV/r 800/100mg in treatment-experienced patients are ongoing

16. ARTEMIS: acknowledgements Argentina: Waldo Belloso, Liiana Calanni, Lidia Cassetti, Luisa De Wouters, Marcelo Losso Australia: Mark Bloch, David Cooper, Dominic Dwyer, Robert Finlayson, Julian Gold, Mark Kelly, Cassy Workman Austria: Armin Rieger, Norbert Vetter Belgium: Nathan Clumeck, Jean-Christophe Goffard, Beatrijs Van der Gucht, Eric Van Wijngaerden Canada: Joss Dewet, Donald Kilby, Patrice Junod, Chris Tsoukas, Sharon Walmsley Chile: Juan Ballesteros, Rebeca Northland Costa Rica: Gisela Herrera, Iris Perez Denmark: Jan Gerstoft, Lars Mathiesen, Henrik Nielsen France: Michelle Bentata, Laurent Cotte, Pierre Dellamonica, Jacques Durant, Pierre-Marie Girard, Christine Katlama, Thierry Prazuck, Dominique Salmon, Patrick Yeni Germany: Keikawus Arasteh, Johannes Bogner, Gerd Fätkenheuer, Frank-Detlef Goebel, Thomas Harrer, Hans Jaeger, Joerg-Andres Rump, Dieter Schuster, Albrecht Stoehr, Jan Van Lunzen Greece: George Chrysos Guatemala: Eduardo Arathoon, Carlos Mejia-Villatoro Italy: Adriano Lazzarin, Anna Maria Orani Malaysia: Christopher Lee Mexico: Jaime Andrade-Villanueva, Gustavo Reyes-Teran, Juan Sierra-Madero, Angelina Villasis-Keever Supported by Tibotec Panama: Amalia Rodriguez, Nestor Sosa Puerto Rico: Javier Morales Ramirez, Carmen Zorrilla- Maldonado Russia: Natalia Dushkina, Oleg Kozyrev, Valery Kulagin, Alexander Pronin, Vladimir Rafalsky, Oleg Romanenko, Elena Vinogradova, Evgeniy Voronin, Alexey Yakovlev Singapore: Poh Lian Lim South Africa: Ezio Baraldi, Francesca Conradie, Jan Fourie, Prudence Ive, Lerato Mohapi, Jennifer Pitt Spain: Buenaventura Clotet, Pere Domingo Switzerland: Milos Opravil Taiwan: Jen-Hsien Wang, Su Pen Yang Thailand: Ploenchan Chetchotisakd, Winai Ratanasuwan, Kiat Ruxrungtham, Khuanchai Supparatpinyo United Kingdom: Martin Fisher, Mark Nelson, Chloe Orkin, Jonathan Weber United States: Ben Barnett, Philippe Chiliade, Amy Colson, Edwin DeJesus, Richard Elion, Walford Fessel, Lucia Flamm, Dushyantha Jayaweera, Peter Kadlecik, Homayoon Khanlou, Lucia Martinez, David McDonough, Anthony Mills, Karam Mounzer, Mahmoud Mustafa, Robert Myers, Jeffrey Nadler, Brian Onbirbak, Roberto Ortiz, Daniel Pearce, Gerald Pierone, Jayashree Ravishankar, Afsoon Roberts, Barry Rodwick, Kunthavi Sathasivam, Stefan Schneider, Michael Sension, Paul Skolnik, Charurut Somboonwit, Aimee Wilkin, Michael Wohlfeiler, Bienvenido Yangco The patients and their families for their participation and support during the study Gilead Sciences for their collaboration The ARTEMIS (TMC114-C211) study team, investigators and co-investigators: