1. Comparison of INSTI vs INSTI  QDMRK  SPRING-2

2. Raffi F. Lancet 2013;381:735-43  Design  Objective –Non inferiority of DTG at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (1-sided significance level of 2.5%, lower margin of the 95% CI for the difference = -10%, 90% power) DTG 50 mg QD + RAL placebo + 2 NRTI** RAL 400 mg BID + DTG placebo + 2 NRTI** Randomisation* 1 : 1 Double-blind > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count No primary resistance in RT or protease *Randomisation (DTG vs RAL) was stratified by HIV RNA ( 100,000 c/mL) at screening and NRTI backbone SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI N = 411 W48W96 SPRING-2 **NRTI backbone (TDF/FTC or ABC/3TC if exclusion of the HLA-B*5701 allele) selected by investigator

3. DTG + 2 NRTI N = 411 RAL + 2 NRTI N = 411 Median age, years3735 Female15%14% HIV RNA (log 10 c/mL), median4.524.58 HIV RNA > 100,000 c/mL28% CD4 cell count (/mm 3 ), median359362 CD4 < 200 per mm 3 13%12% Hepatitis B / hepatitis C coinfection2% / 10%2% / 9% Dual NRTI on day 1 : TDF/FTC / ABC/3TC59% / 41%60% / 40% Discontinuation by W4847 (11.4%)56 (13.6%) For virologic failureN = 16N = 24 For adverse event / For liver stopping criteriaN = 8 / N = 2N = 6 / N = 1 Lost to follow-upN = 4N = 7 Protocol deviation / Withdrew consentN = 13 / N = 4N = 11 / N = 7 Discontinuation by W9662 (15%)79 (19%) Baseline characteristics and patient disposition Raffi F. Lancet 2013;381:735-43 ; Raffi F. Lancet Infect Dis 2013; 13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

4. Response to treatment at week 48 Median CD4/mm 3 increase at W48 : + 230 in both groups Non-inferiority was also supported by Kaplan-Meier estimates of the proportion of patients without virological failure by week 48 The number of patients who achieved the primary endpoint was similar between subgroups in analyses that combined high and low HIV RNA strata and backbone NRTI 25 50 100 75 87.8 85.4 Adjusted difference (95% CI) = 2.5% (- 2.2 ; 7.1) 89.9 88.4 Adjusted difference (95% CI) = = 1.6% (- 2.7 ; 5.9) ITT, snapshotPer protocol DTG + 2NRTI RAL + 2 NRTI HIV RNA < 50 c/mL Primary analysis % 0 Raffi F. Lancet 2013;381:735-43 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

5. DTG 50 mg QD N = 411 RAL 400 mg BID N = 411 Difference in % (95% CI) DTG – RAL Number of Responders/Number Assessed Baseline Plasma HIV-1 RNA ≤ 100,000 c/mL 267 / 297 (90%)264 / 295 (89%)0.4 (-4.5, 5.3) >100,000 c/mL 94 / 114 (82%)87 / 116 (75%)7.5 (-3.1, 18.0) P = 0.236* Background Dual NRTI ABC/3TC 145 / 169 (86%)142 / 164 (87%)-0.8 (-8.2, 6.6) TDF/FTC 216 / 242 (89%)209 / 247 (85%)4.6 (-1.3, 10.6) P = 0.264* * Test for homogeneity HIV-1 RNA < 50 c/mL at week 48 by stratification factors Raffi F. Lancet 2013;381:735-43 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

6. Response to treatment at week 96 25 50 100 75 80.8 76.4 % Adjusted difference (95% CI) = 4.5 % (- 1.1 ; 10.0) 83.5 80.4 Adjusted difference (95% CI) = 3.2 % (- 2.1 ; 8.6) ITT, snapshotPer protocol 25 50 100 75 78 63 % > 100,000 HIV-1 RNA (c/mL)NRTI backbone 74 76 DTG + 2 NRTI RAL + 2 NRTI HIV RNA < 50 c/mL at week 96 0 0 ITT snapshot, by baseline stratification factors ≤ 100,000TDF/FTCABC/3TC 82 86 77 Raffi F. Lancet Infect Dis 2013;13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

7. Raffi F. Lancet Infect Dis 2013;13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI  Virologic non-responders (ITT, snapshot) at week 96 by baseline stratification factors SPRING-2 DTG 50 mg QD N = 411 RAL 400 mg QD N = 411 Baseline HIV-1 RNA < 100,000 c/mL10/297 (3)17/295 (6) Baseline HIV-1 RNA > 100,000 c/mL12/114 (11)26/116 (22) ABC/3TC10/169 (6)16/164 (10) TDF/FTC12/242 (5)27/247 (11) ABC/3TC (N = 169) TDF/FTC (N = 242) ABC/3TC (N = 164) TDF/FTC (N = 247) Baseline HIV-1 RNA < 100,000 c/mL6/132 (5)4/165 (2)8/125 (6)9/170 (5) Baseline HIV-1 RNA > 100,000 c/mL4/37 (11)8/77 (10)8/39 (21)18/77 (23)

8.  Virologic failure definition –2 consecutive plasma HIV-1 RNA > 50 c/mL, on or after W24  Criteria for resistance testing –All patients with protocol defined virologic failure (PDVF) –Genotype of RT and integrase on baseline and suspected virologic failure samples DTG + 2 NRTI, N = 411RAL + 2 NRTI, N = 411 D0-W48W48-W96D0-W48W48-W96 PDVF20 (4.9%)228 (6.8%)1 Integrase genotype results at baseline and time of PDVF 82181 Emergent integrase-resistance mutations001*0 Reverse transcriptase genotype results at baseline and time of PDVF 122191 Emergent NRTI-resistance mutations004*0 * 1 patient with INSTI mutations (T97T/A, E138E/D, V151V/I, N155H) and NRTI mutations (A62A/V, K65K/R, K70K/E, M184V), 1 patient with M184M/I, 1 with M184M/V, 1 with A62A/V Resistance data at PDVF Raffi F. Lancet 2013;381:735-43 ; Raffi F. Lancet Infect Dis 2013;13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

9. DTG + 2 NRTIRAL + 2 NRTI Any adverse event82%83% AE in > 5% of subjects in either group Nausea14%13% Headache12% Nasopharyngitis11%12% Diarrhoea11% Upper respiratory tract infection6% Dizziness6% Pyrexia5% Fatigue5%4% Insomnia5%4% Bronchitis5%4% Depression5%3% Pharyngitis5%3% Influenza3%5% Asthenia3%5% Syphilis2%5%  Adverse events at week 48 Raffi F. Lancet 2013;381:735-43 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

10. DTG + 2 NRTIRAL + 2 NRTI Any serious adverse eventN = 29 (7.1%)N = 31 (7.3%) SAE related to study drugN = 3N = 5 Aphasia0N = 1 ArrhythmiaN = 10 Convulsion0N = 2* Diarrhoea0N = 1 HepatitisN = 10 HypersensitivityN = 1 CPK increased0N = 1*  Serious adverse events at week 48 * 1 patient with elevated CPK + convulsion  Safety between W48 and W96 –Adverse events leading to discontinuation : 0 for DTG vs 3 for RAL –No serious adverse events related to study drugs Raffi F. Lancet 2013;381:735-43 ; Raffi F. Lancet Infect Dis 2013; 13:927-35  Graded laboratory toxic effects : rates similar between groups SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2

11. Raffi F. Lancet Infect Dis 2013;13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI  Mean change in serum creatinine concentration (µmol/L) from baseline SPRING-2  Mean change in estimated creatinine clearance (CG formula) at W96 : –- 19.6 mL/min for DTG vs – 9.3 mL/min for RAL  No discontinuations due to renal events through 96 weeks Baseline4812162432404860728496 12.3 14.6 4.7 8.2 -20 -10 0 10 20 30 40 DTG 50 mg QD RAL 400 mg BID

12.  Conclusion –DTG 50 mg QD was virologically non-inferior to RAL BID, (both + 2 NRTIs) over 48 and 96 weeks –No INSTI mutations were detected through 96 weeks with DTG –DTG was similar to RAL in terms of safety and tolerability –Low occurrence of adverse events leading to discontinuation : 2% in each group –Between W48 and W96 : few new virologic failures and few discontinuations for adverse events –No discontinuation due to renal events through 96 weeks –Mean increases in creatinine with accompanying decreases in estimated glomerular filtration rate occurred in both study groups by week 4 generally stabilised and did not change up to week 96 Raffi F. Lancet 2013;381:735-43 ; Raffi F. Lancet Infect Dis 2013;13:927-35 SPRING-2 Study: DTG QD + 2 NRTI vs RAL BID + 2 NRTI SPRING-2