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-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Design Randomisation* 1 : 1 Double-blind W48 W144 > 18 years, ARV-naïve HIV RNA > 500 c/mL Any CD4 cell count HLA B*5701 negative eGFR ≥ 50 mL/min HBs Ag negative No resistance to FTC/3TC, TDF or ABC N = 314 BIC/F/TAF QD DTG/ABC/3TC placebo QD N = 315 DTG/ABC/3TC 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-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print 2

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Baseline characteristics and patient disposition BIC/F/TAF N = 314 DTG/ABC/3TC N = 315 Median age, years 31 32 Female, % 9 10 HIV RNA (log10 c/mL), median 4.42 4.51 HIV RNA > 100 000 c/mL, % 17 16 CD4 cell count (/mm3), median 443 450 CD4 < 200/mm3, % 11 Discontinuation by W48, % 6 5 For lack of efficacy, N For adverse event, N 4 Lost to follow-up, N Non-compliance / Other, N 1 / 9 1 / 5 GS-US-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print 3

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Virologic outcome at week 48 BIC/F/TAF DTG/ABC/3TC 92.4 1.0 6.7 93.0 2.5 4.4 20 40 60 80 100 HIV RNA < 50 c/mL ≥ 50 c/mL No data % DTG/ABC/3TC BIC/F/TAF ‒ 12% + 12% 3.6 - 4.8 - 0.6 Difference (95 % CI) Met criteria for resistance testing (HIV RNA ≥ 200 c/mL) BIC/F/TAF: 1 vs DTG/ABC/3TC: 4 No resistance emergence Mean CD4 increase at W48 BIC/F/TAF: + 233/mm3 DTG/ABC/3TC: + 229/mm3 HIV RNA < 50 c/mL (per-protocol) BIC/F/TAF: 99.3% DTG/ABC/3TC: 98.6% GS-US-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print 4

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Adverse events BIC/F/TAF N = 314 DTG/ABC/3TC N = 315 Adverse events leading to study drug discontinuation, N 4 * Adverse event ≥ 5% in either group, % Diarrhea Headache Nausea Nasopharyngitis Cough Upper respiratory tract infection Fatigue Syphilis Insomnia Arthralgia Vomiting Bronchitis Abdominal pain 12.7 11.5 10.2 7.3 6.4 6.4 6.1 3.8 4.5 3.5 3.8 3.2 2.9 13.0 13.7 22.9 ** 9.2 2.5 10.8 8.6 7.9 6.3 6.0 5.4 5.1 5.1 Grade 3-4 laboratory abnormalities, % CK elevation LDL-cholesterol elevation Amylase Neutropenia 3.5 2.3 1.9 1.6 3.3 2.6 2.2 3.2 * Nausea, rash ; thrombocytopenia ; chronic pancreatitis, steatorrhea ; depression ** p < 0.001 GS-US-380-1489 Gallant J. IAS 2017, Abs. MOAB0105LB ; Gallant J. Lancet 2017, Aug 31, ePub ahead of print 5

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Renal parameters, bone mineral density and lipid changes at W48 BIC/F/TAF N = 314 DTG/ABC/3TC N = 315 Median change in eGFR (Cockroft-Gault), mL/min - 10.5 - 10.8 Median percent changes in quantitative proteinuria, % Urine albumin: creatinine Retinol binding protein : creatinine Beta2-microglobulin : creatinine 0.6 14 - 23 6 20 - 18 Mean % changes in bone mineral density, % Hip Spine - 0.6 - 0.78 - 0.83 - 1.02 Mean changes in fasting lipids, mg/dL Total cholesterol LDL cholesterol HDL cholesterol Triglycerides 13 7 5 9 11 4 3 None of the differences between groups were significant No discontinuations due to renal adverse events and no proximal tubulopathy in either arm GS-US-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print 6

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17) Bictegravir FTC TAF AUCtau (hr*ng/mL) Mean (% CV ; min-max 96 181.5 (33.5 ; 36 194-154 317) 10 896.4 (29.8 ; 5 602.3-20 773.3) 206.0 (51.2 ; 101.5-458.4) Cmax (ng/mL) Mean (% CV ; min-max) 6 704.7 (27.5 ; 3 550-9 550) 1 868 (34.5 ; 822-3 220) 225.5 (68.3 ; 73.3-713) Ctau (ng/mL) * 2 311.7 * (40.7 ; 429-4 030) 80.9 (37.1 ; 39.5-172.0) - Tmax (h) Median (Q1-Q3) 1.53 (1.00-2.07) 1.50 (1.00-1.55) 0.53 (0.50-1.03) t1/2 (h) 15.93 (14.50-17.78) 6.66 (6.32-7.17) 0.42 (0.36-0.49) * BIC mean Ctau about 14 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus. GS-US-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD ARV-trial.com Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Summary of week 48 results Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W48 by snapshot algorithm 92.4% of patients on BIC/F/TAF and 93.0% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL Sensitivity analyses confirmed non inferiority No treatment emergent resistance BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001) Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC Changes from baseline in bone mineral density, lipid parameters and renal markers were comparable between treatment arms GS-US-380-1489 Gallant J. Lancet 2017, Aug 31, ePub ahead of print 8