1. XVIII International AIDS Conference 18-23 July 2010, Vienna, Austria Shionogi-ViiV Healthcare LLC Activity of Next Generation Integrase Inhibitor (INI) S/GSK1349572 in Subjects with HIV Exhibiting Raltegravir Resistance: Initial Results of VIKING Study (ING112961) J. Eron 1, J. Durant 2, I. Poizot-Martin 3, J Reynes 4, V Soriano 5, P Kumar 6, G Richmond 7, D Vittecoq 8, T Fujiwara 9, M Ait-Khaled 10, S Min 11, D Thomas 11, R Cuffe 10, J Yeo 10 1 Center for AIDS Research Clinical Core, UNC School of Medicine, NC; 2 Hôpital l'Archet, Nice; 3 Hôpital Sainte Marguerite, Marseille; 4 Hôpital Guide Chauliac, Montpellier; 5 Hospital Carlos III, Madrid; 6 Georgetown Univ, Washington; 7 Fort Lauderdale; 8 Hôpital Paul Brousse, Villejuif; 9 Shionogi & Co., Ltd., Osaka, Japan; 10 GlaxoSmithKline, London; 11 GlaxoSmithKline, Research Triangle Park, NC

2. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Background ●Virologic failure occurred in 23% of treatment experienced subjects receiving raltegravir (RAL) in BENCHMRK-1 and 2 –70% harbored virus with RAL-resistance signature mutations –3 RAL-resistance pathways – Y143, Q148 and N155 –Additional substitutions increase resistance and/or fitness ●In vitro susceptibility to S/GSK1349572, suggested two RAL-resistant viral populations: –Variable increase in fold-change (FC) to S/GSK1349572 (Q148 plus secondary mutations) –No or minimal increase in FC to S/GSK1349572 (N155 pathway, Y143 pathway, Q148 single mutants) ●The clinical evaluation of S/GSK1349572 in subjects with RAL-resistant virus is warranted

3. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria VIKING Study Design Cohort I ●Current or historic RAL-failures with evidence of RAL-resistance ●At least 3 ART-class resistant (includes INI) ●All subjects receive S/GSK1349572 50mg QD Allocated to one of two groups based on genotype at screen to ensure broad sensitivity range Functional Monotherapy Phase Replace RAL with S/GSK1349572 or add, if RAL already stopped Continuation Phase S/GSK1349572 + OBR Day 1Day 11Week 24 *Q148H/K/R plus changes in L74 and/or E138 and/or G140 **N155H and Y143H pathways or Q148H/K/R single mutants Q148H/K/R + one or more secondary resistance mutations* N~ 15 All other mutations (including codon 148 single mutation)** N~ 15

4. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria VIKING Objectives and End-points ●Primary Objective –To assess the short-term antiviral activity of S/GSK1349572 + failing background regimen ●Primary End-point –Proportion of subjects with Day 11 plasma HIV-1 RNA <400c/mL or at least 0.7 log 10 c/mL below their Baseline value ●Secondary End-points –Includes measures of safety, antiviral response, INI-resistance emergence and pharmacokinetic parameters at Day 11 and over time

5. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Baseline Characteristics Enrolled, (N) 27 Age in years, median (range) 48 (19-61) Males : females 25 : 2 CD4+ cells/mm 3, median (IQ)110 (40, 230) CD4+ <50 cells/mm 3, n (%) 7 (26%) Plasma HIV-1 RNA log 10 c/mL, median (IQ)4.47 (3.9, 4.9) Plasma HIV-1 RNA >50,000 c/mL, n (%) 9 (33%) CDC class C, n (%)16 (59%) Current RAL failure21 (78%) Historic RAL failure6 (22%) Duration of prior ART in years, median (range)14 (4-21) Number of prior ART, median (range)17 (6-24) Prior ART exposure: Etravirine, n (%) Enfuvirtide, n (%) Darunavir/r, n (%) Maraviroc, n (%) 19 (70%) 22 (81%) 23 (85%) 10 (37%)

6. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Baseline (Day 1) Viral IN Mutation Pathways and Phenotypic Susceptibility to S/GSK1349572 ●More advanced Q148 pathway genotypes exhibit higher fold change to S/GSK1349572 Baseline 572 Fold Change Baseline Mutation Pathway Q148+2 n=3 Q148+1 n=4 N155 n=4 Mixture n=2 Other IN mutations n=2 Y143 n=12 Fold Change, median (range): RAL 161 (0.6 - >166) S/GSK1349572 1.5 (0.6 - 35) Mixtures: n=1 Q148H + G140S / Y143H n=1 Q148H+ E138A+G140S / Y143H Others: n=1 E92Q (screen: E92Q, N155H) n=1 none (screen: G140G/S, Q148H/Q) 20 10 6 4 2 1 0.6

7. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Plasma HIV-RNA Response at DAY 11 by Viral IN Baseline Genotypic Profile Primary End-point HIV-1 RNA <400c/mL or ≥0.7 log 10 c/mL decline in HIV-1 RNA n/N (%) Secondary End-point HIV-1 RNA log 10 c/mL change from baseline Mean (SD) All subjects 21/27 (78%) -1.45 (SD 0.76) Q148H/K/R + ≥1 Q148 associated mutations at L74, E138 or G140 (n=9) 3/9* (33%) -0.72 (SD 0.63) All other genotypes from N155H and Y143H pathways (n=18) 18/18 (100%) -1.82 (SD 0.53) * Halted enrollment early in this group due to less robust virologic response

8. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Virologic Response at DAY 11: Correlation with Baseline Fold Change (FC) in Susceptibility to S/GSK1349572 Mixtures: N=1 Q148H + G140S / Y143H N=1 Q148H+ E138A+G140S / Y143H Others: N=1 E92Q (screen: E92Q, N155H) N=1 none (screen: G140G/S, Q148H/Q) Strong correlation between baseline FC and Day 11 response (r=0.79, p value <0.001) 0.51.02.05.010.020.0 -2.5 -2.0 -1.5 -0.5 Day 1 S/GSK1349572 Fold Change Day 11 VL Change From Baseline (log 10 c/mL) Y143 N155 Other Q148 + 2 Q148 + 1 Mixture

9. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria HIV IN Genotypic and Phenotypic Changes at Day 11 ●18* paired viral isolates (Day 1 & Day 11) were evaluated ●No signature RAL mutations emerged on therapy ●17 paired isolates: susceptibility change was <2 fold ●1 paired isolate: susceptibility change was ~6-fold ●Detailed resistance data presented by Clotet B et al. TUPE0130 IAC 2010 *Viral load too low to analyze genotype and phenotype in remaining isolates at Day 11

10. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Adverse Events ●Most common clinical AEs (>1 subject): Diarrhea & insomnia (3/27 subjects, 11%) ●Grade 3/4 clinical AEs: 3 (11%) subjects –Grade 3: syncope & vertigo (n=1), hypercholesterolaemia (n=1) –Grade 4: neurosyphilis (n=1) ●Drug related AEs: 4 (15%) subjects –Grade 1: diarrhoea & nausea (n=1), anaemia (n=1) –Grade 2: fatigue & insomnia (n=1), diarrhoea (n=1) ●Grade 3 laboratory toxicities: 6 (22%) subjects –1 amylase increase –1 total cholesterol increase –2 lipase increase –2 phosphorus decrease ●No Grade 4 laboratory toxicities ●Serious Adverse Events: 2 (7%) subjects, neither considered related to S/GSK1349572 –1 neurosyphilis ~ Wk 1 –1 brain mass ~ Wk 6 Median (min, max) exposure: 56 (28, 87) days

11. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria VIKING Study Conclusions ●Baseline isolates exhibited high FC in susceptibility to RAL (median 161) with substantially lower FC in susceptibility to S/GSK1349572 (median 1.5). –A broad spectrum of susceptibility to S/GSK1349572 ranging from 0.6 to 35 was observed ●21/27 (78%) subjects achieved the primary end-point (<400c/mL or a ≥0.7log10c/mL decline in plasma HIV-1 RNA) at Day 11 –18/18 subjects with isolates exhibiting the N155H, Y143H pathways achieved the primary end-point ●A strong correlation was observed between change from baseline in plasma HIV-1 RNA and baseline fold change in susceptibility to S/GSK1349572 ●S/GSK1349572 was generally well tolerated in this advanced HIV-1 infected population

12. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria Acknowledgments ●All SUBJECTS who participated in VIKING in the screening or treatment phases ●VIKING Investigators: –France: Jacques Reynes, Isabelle Poizot-Martin, Jacques Durant, Philippe Morlat, Daniel Vittecoq, Christine Katlama, Jean-Michel Livrozet –Italy: Adriano Lazzarin –Spain: Bonaventura Clotet, Vincente Soriano –USA: Edwin DeJesus, Joseph J. Eron Jr., Trevor Hawkins, Princy Kumar, Jacob P Lalezari, Anthony LaMarca, Gary J Richmond, Louis A Sloan, Benjamin Young ●Contributors from GSK, SHIONOGI and ViiV HC

13. XVIII International AIDS Conference 18-23 July 2010, Vienna, Austria Shionogi-ViiV Healthcare LLC Backups 13

14. XVIII International AIDS Conference, 18-23 July 2010, Vienna, Austria S/GSK1349572 Day 10 PK Parameters AUC(0-  ), ug*h/mL Cmax, ug/mL C , ug/mL 50mg QD (n=25)36.5 (53%)3.04 (38%)0.69 (91%) Geometric Mean (95% Confidence Interval) GSK1349572 PK observed in VIKING is consistent with accumulated PK data in humans.