1. Comparison of INSTI vs EFV  STARTMRK  GS-US-236-0102  SINGLE

2. Walmsley S. NEJM 2013;369:1807-18  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 + ABC/3TC FDC QD TDF/FTC/EFV placebo TDF/FTC/EFV QD DTG placebo + ABC/3TC placebo Randomisation* 1 : 1 Double-blind > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count HBsAg negative No genotypic resistance HLA-B*5701 negative *Randomisation was stratified by HIV RNA ( 100,000 c/mL) and CD4/mm 3 ( 200) at screening SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD N = 422 W96W144 SINGLE Open-label

3. DTG + ABC/3TC N = 414 TDF/FTC/EFV N = 419 Median age, years3635 Female16%15% HIV RNA (log 10 c/mL), median4.674.70 HIV RNA > 100,000 c/mL32%31% CD4 cell count (/mm 3 ), median335339 CD4 < 200 per mm 3 14%15% Hepatitis C coinfection7% Discontinuation by W4851 (12.3%)84 (20.0%) For lack of efficacyN = 14N = 13 For adverse eventN = 10N = 42 Lost to follow-upN = 14N = 9 Protocol deviation / Withdrew consentN = 7 / N = 5N = 7 / N = 11 Baseline characteristics and patient disposition Walmsley S. NEJM 2013;369:1807-18 SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE

4. Response to treatment at week 48 Adjusted mean CD4/mm 3 increase at W48 : + 267 for DTG + ABC/3TC + 208 for TDF/FTC/EFV (p<0.001) Differences in viral suppression were also seen in key demographic subgroups including race, sex, age and patients with HIV RNA > 100,000 c/mL at baseline 25 50 100 75 87.9 80.7 Adjusted difference (95% CI) = 7% (2; 12) 89.8 81.3 Adjusted difference (95% CI) = 9% (4; 13) ITT, snapshotPer protocol DTG + ABC/3TC TDF/FTC/EFV HIV RNA < 50 c/mL Primary analysis % 0  Superiority of DTG + ABC/3TC Walmsley S. NEJM 2013;369:1807-18 SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE

5. Response to treatment at week 96 SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE HIV-1 RNA < 50 c/ml (ITT, snapshot) Walmsley S, CROI 2014, Abs. 543

6. Pappa K. ICAAC 2014, Abs. H-647a. SINGLE HIV-1 RNA < 50 c/mL at W144, ITT snapshot SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD Virologic success Virologic non-response No virologic data Favors EFV/TDF/FTC 95% CI for Difference 0 -5% W48 W96 W144 7.4% 8.0% 8.3% 2.5% 2.3% 2% 14.6% 13.8% 12.3% Favors DTG+ABC/3TC 15% 88 80 71 5 7 10 7 12 18 81 72 63 6 8 7 13 20 30 0 20 40 60 80 100 W48W96W144W48W96W144W48W96W144 DTG + ABC/3TC (N=414) TDF/FTC/EFV (N=419) %

7. HIV-1 RNA < 50 c/mL by baseline stratification factors Walmsley S. NEJM 2013;369:1807-18; Pappa K. ICAAC 2014, Abs. H-647a SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE W48 outcome DTG + ABC/3TCTDF/FTC/EFV Plasma HIV-1 RNANumber of Responders/Number Assessed ≤100,000 c/mL 253/280 (90.4%)238/288 (82.6%) >100,000 c/mL 111/134 (82.8%)100/131 (76.3%) CD4+ T cell count > 200/mm 3 319/357 (89.4%)290/357 (81.2%) < 200/mm 3 45/57 (78.9%)48/62 (77.4%) W144 outcome Plasma HIV-1 RNA ≤100,000 c/mL 204/280 (73%)185/288 (64%) >100,000 c/mL 92/134 (69%)80/131 (61%) CD4+ T cell count > 200/mm 3 262/357 (73%)230/357 (64%) < 200/mm 3 34/57 (60%)35/62 (56%)

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 + ABC/3TC, N = 414TDF/FTC/EFV, N = 419 D0-W48W48-96W96-144D0-W48W48-96W96-144 PDVF18 (4.3%)71417 (4.1%)88 Integrase genotype at baseline and time of PDVF 7--7-- Emergent integrase-R mutations0*00000 RT genotype results at baseline and time of PDVF 9--9-- Emergent NRTI-R mutations Emergent NNRTI-R mutations 0000 0000 0000 1 (K65R) 4** 0 2*** 0000 * E157Q/P polymorphism in 1 patient with no change in phenotype ** N = 1 with K101E, N = 1 with K103N, N = 1 with G190A, N = 1 with K103N + G190A ; **** N = 2 with K103K/N Resistance data at PDVF Walmsley S, ICAAC 2012, Abs.H556b ; Walmsley S. NEJM 2013;369:807-18 ; Walmsley S, CROI 2014, Abs.543 ; Pappa K. ICAAC 2014, Abs. H-647a SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE

9. DTG + ABC/3TCTDF/FTC/EFV Adverse event leading to discontinuation of study drug10 (2.4%)42 (10.0%) Psychiatric disorder, N215 Nervous system disorder, N013 Skin and subcutaneous-tissue disorder, N28 Gastrointestinal disorder, N08 General disorder or administration-site condition, N07 Adverse event of grade 2-4 in > 3% in either group Bronchitis2%3% Diarrhoea5%4% Nausea2%3% Insomnia4% Anxiety2%3% Depression2%3% Headache3% Dizziness< 1%5% Rash1%5% Grade 2-4 elevation of ALT2%5% Grade 2-4 elevation of AST2%5% Adverse events and laboratory abnormalities at week 48 Walmsley S. NEJM 2013;369:1807-18 SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE

10. Walmsley S. NEJM 2013;369:1807-18 ; Pappa K. ICAAC 2014, Abs. H-647a SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD  Insomnia was more frequent in DTG group at W48 (15% vs 10%)  Mean change in creatinine at W48 on DTG: + 0.12 to 0.15 mg/dL (10.56 to 13.2 mmol/L), peak at W2, then stable SINGLE DTG + ABC/3TCTDF/FTC/EFV At week 48N = 1N = 8 Suspected drug hypersensitivity, N = 1 Psychiatric event, N = 4 Drug hypersensitivity, N = 2 Cerebrovascular accident, N = 1 Renal failure, N = 1 Between W48 and W144N = 1 OsteonecrosisSyncope Serious adverse events related to study drug

11.  Conclusion –DTG + ABC/3TC QD had a better safety profile and was superior through 48 weeks to TDF/FTC/EFV for first-line antiretroviral therapy Superior virologic response with DTG + ABC/3TC also seen in key demographic subgroups and in patients with low or high baseline viral load Statistical superiority in CD4 response for DTG + ABC/3TC Virologic superiority of DTG + ABC/3TC confirmed at W96 and W144 –No INSTI major mutations were detected through 144 weeks with DTG –Lower occurrence of adverse events leading to discontinuation with DTG : 2% vs 10% at W48 ; 4% vs 14% at W144 –Significant lower reported rates of neuro-psychiatric and rash events with DTG + ABC/3TC Except for insomnia (15% vs 10% at W48) Walmsley S. NEJM 2013;369:807-18 ; Walmsley S, CROI 2014, Abs.543 ; Pappa K, ICAAC 2014, Abs. H-647a SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE