Comparison of INSTI vs INSTI ARV-trial.com Comparison of INSTI vs INSTI QDMRK SPRING-2 ONCEMRK GS-US-380-1489 GS-US-380-1490 1

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Design Randomisation* 1 : 1 Double-blind W48 W144 > 18 years ARV-naïve HIV RNA > 500 c/mL Any CD4 cell count eGFR ≥ 30 mL/min No resistance to FTC or TDF HBV or HCV co-infection allowed N = 320 BIC/F/TAF QD DTG + F/TAF placebo QD N = 325 DTG + F/TAF QD BIC/F/TAF placebo QD * Randomisation was stratified by HIV RNA (< 100 000 c/mL, 100 000-4000 000 c/mL or > 100 000 c/mL), CD4 (< 50/mm3, 50-199/mm3 or ≥ 200/mm3) at screening and geographic region (USA vs non-USA) BIC/F/TAF: 50/200/25 mg, as STR Objective Non inferiority of BIC/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided 95.002% CI for the difference= -12%, 95% power) GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 2

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Baseline characteristics and patient disposition BIC/F/TAF N = 320 DTG + F/TAF N = 325 Median age, years 33 34 Female, % 12 11 HIV RNA (log10 c/mL), median 4.43 4.45 HIV RNA > 100 000 c/mL, % 21 17 CD4 cell count (/mm3), median 440 441 CD4 < 200/mm3, % 14 10 HBV/HCV co-infection, % 3 / 2 2 /2 Discontinuation by W48, N (%) For lack of efficacy, N For adverse event, N Lost to follow-up, N Non-compliance, N Patient decision / investigator discretion, N Other, N 28 (9 %) 0 5 8 0 7 / 4 4 20 (6 %) 0 1 5 2 7 / 0 5 Discontinuation W48-W96, N (%) 1 16 (5 %) 0 4 GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 ; Stellbrink HJ, HIV Glasgow 2018, Abs. 0211 3

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Virologic outcome at week 48 89.4 4 6 92.9 1 20 40 60 80 100 HIV RNA < 50 c/mL ≥ 50 c/mL No data % BIC/F/TAF (N = 320) DTG + F/TAF (N = 325) DTG + F/TAF BIC/F/TAF ‒ 12% + 12% 1.0 - 7.9 - 3.5 Difference (95 % CI) Met criteria for resistance testing (HIV RNA ≥ 200 c/mL) BIC/F/TAF: 7 vs DTG + F/TAF: 5 No resistance emergence Mean CD4 increase at W48 BIC/F/TAF: + 180/mm3 DTG + F/TAF: + 201/mm3 HIV RNA < 50 c/mL (per-protocol) BIC/F/TAF: 98.9% DTG + F/TAF: 99.7% GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 . 4

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Virologic outcome at week 96 BIC/F/TAF (N = 320) DTG + F/TAF (N = 325) 84 4 12 86 3 11 20 40 60 80 100 HIV RNA < 50 c/mL ≥ 50 c/mL No data % DTG + F/TAF BIC/F/TAF ‒ 12% + 12% 3.2 - 7.9 - 2.3 Difference (95 % CI) Met criteria for resistance testing (HIV RNA ≥ 200 c/mL) BIC/F/TAF: 7 vs DTG + F/TAF: 6 No resistance emergence Mean CD4 increase at W96 BIC/F/TAF: + 237/mm3 DTG + F/TAF: + 281/mm3 HIV RNA < 50 c/mL (per-protocol) BIC/F/TAF: 100% DTG + F/TAF: 98.2% p = 0.008 GS-US-380-1490 Stellbrink HJ, HIV Glasgow 2018, Abs. 0211 5

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Adverse events at W48 BIC/F/TAF, N = 320 DTG + F/TAF, N = 325 Adverse event ≥ 5% in either group, % Headache Diarrhea Nausea Nasopharyngitis Fatigue Influenza Lymphadenopathy Arthralgia Insomnia Upper respiratory tract infection Pyrexia Back pain 12.5 11.6 7.8 6.9 5.9 5.3 5.3 5.0 5.0 4.7 4.4 3.4 12.3 12.0 8.9 9.5 8.0 3.1 5.5 2.8 4.3 7.1 6.5 6.2 Grade 3-4 laboratory abnormalities, % CK elevation LDL-cholesterol elevation ALT / AST elevation Hyperglycemia 3.5 3.0 2.2 / 1.3 0.3 2.2 3.5 0.9 / 2.5 2.2 GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 6

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Drug-related adverse events at W96, % BIC/F/TAF, N = 320 DTG + F/TAF, N = 325 Any 20 28 ( p = 0.02) Nausea Diarrhea Headache 3 3 4 5 3 3 Adverse events leading to study drug discontinuation, D0-W96, N BIC/F/TAF N = 320 DTG + F/TAF N = 325 N total 6 5 Between D0 and W48 Atypical chest pain Sleep disorder/tension headache/depressed mood/insomnia/dyspepsia Cardiac arrest (sepsis/appendicitis) Paranoia Abdominal distension 1 Erythema/pruritus Between W48 and W96 Depression 4 Depression (n = 2) Lipoatrophy Supraventricular tachycardia Stellbrink HJ, HIV Glasgow 2018, Abs. 0211 7

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Median change from baseline in eGFR and lipids BIC/F/TAF N = 314 DTG + F/TAF N = 315 p eGFR (Cockroft-Gault), mL/min, D0 to W48 - 7.3 - 10.8 0.0181 Fasting lipids, mg/dL, D0 to W48 Total cholesterol LDL cholesterol HDL cholesterol Triglycerides Fasting lipids, mg/dL, D0 to W96 12 9 5 3 17 19 4 6 15 12 5 7 16 5 ns No discontinuations due to renal adverse events and no proximal tubulopathy in either arm GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 ; Stellbrink HJ, HIV Glasgow 2018, Abs. 0211 8

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17) Bictegravir FTC TAF AUCtau (hr*ng/mL) Mean (% CV ; min-max) 101 120.5 (43.8 ; 55 065.7-216 295) 11 238.1 (28.4 ; 5 621.6-18 876.7) 259.4 (59.9 ; 63.1-710.2) Cmax (ng/mL) 7 339.4 (37.3 ; 4 170-13 300) 1 920 (20.7 ; 1 380-2 820) 309.4 (59.9 ; 63.3-764) Ctau (ng/mL) * 2 576.0 ** (52.0 ; 800-5 690) 97.7 (38.4 ; 47-169) - Tmax (h) Median (Q1-Q3) 1.02 (1.00-2.97) 1.02 (1.00-1.50) 0.50 (0.50-1.02) t1/2 (h) 18.56 (15.51-20.14) 7.05 (6.39-7.35) 0.43 (0.31-0.56) * N = 15 ** BIC mean Ctau about 16 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus Sax PE. Lancet. 2017 ;390:2073-82. 9

Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD ARV-trial.com Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD Summary of week 96 results Virologic suppression at W48 and W96 was high in both arms, with BIC/F/TAF being non inferior to DTG + F/TAF in treatment-naïve adults Sensitivity analyses confirmed BIC/F/TAF was non inferior to DTG + F/TAF No patient discontinued either treatment arm due to lack of efficacy No treatment-emergent resistance to any study medication was observed in either arm BIC/F/TAF was safe and well tolerated Less decrease in eGFRCG was observed with BIC/F/TAF vs DTG + F/TAF at W48 There were no discontinuations due to renal adverse events and no cases of renal tubulopathy, including Fanconi syndrome, in either treatment group Changes from baseline in lipid parameters were equivalent GS-US-380-1490 Sax PE. Lancet. 2017 ;390:2073-82 ; Stellbrink HJ, HIV Glasgow 2018, Abs. 0211 10