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 DTG/ABC/3TC QD BIC/F/TAF placebo QD N = 315 * 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 Nov 4;390(10107):2063-2072 ; Wohl DA Lancet HIV 2019 ; 6:e355-63 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 Discontinuations at W48 W48-W96 Total discontinuations, N (%) 19 (6%) 17 (5.8%) 16 (5%) 15 (5%) For lack of efficacy, N For adverse event, N 4 1 Lost to follow-up, N 8 6 Non-compliance / Other, N 1 / 9 1 / 8 1 / 5 2 / 6 GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072 ; Wohl DA Lancet HIV 2019 ; 6:e355-63 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 Nov 4;390(10107):2063-2072 4

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD HIV RNA < 50 c/mL at W48 according to baseline CD4 and HIV RNA, ITT-E snapshot > 100 000 ≤ 100 000 > 200 ≤ 200 HIV RNA, c/ml CD4/mm3 20 40 60 80 100 93 94 87 90 83 81 % N= 261 265 53 50 278 283 36 32 BIC/F/TAF DTG/ABC/3TC GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072

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 at W48 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. Lancet. 2017 Nov 4;390(10107):2063-2072 6

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 Nov 4;390(10107):2063-2072 7

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 Nov 4;390(10107):2063-2072

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 Nov 4;390(10107):2063-2072 9

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Virologic outcome at week 96, ITT snapshot BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) HIV RNA < 50 c/mL ≥ 50 c/mL No virologic data 87.9 0.6 89.8 2.2 11.5 7.9 % 100 80 60 40 20 Difference (95 % CI) -12 % 12 % DTG/3TC/ABC BIC/F/TAF - 1.9 3.1 - 6.9 Secondary endpoints at week 96 BIC/F/TAF DTG/3TC/ABC HIV RNA < 50 c/mL (sensitivity analyses) Per protocol 99.6% 98.9% Missing = failure 87.9% 90,8% Missing = excluded 99.3% Virologic failure with confirmed HIV RNA > 200 c/mL N assessed for resistance N with emergence of resistance 5 Mean change in CD4 at W96 + 287/mm3 + 288/mm3 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Adverse events at W96 Discontinuation for adverse event BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) 5 (1.6%) Nausea, rash (D4) Thrombocytopenia (D50) Chronic pancreatitis (D134) Depression (D248) Renal failure (D621) Adverse events all grades (%) BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) Nausea 11 * 24 * Headache 13 16 Diarrhea 15 Fatigue 9 11 Insomnia 7 10 * p < 0.001 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Laboratory parameters (W96) BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) p CK grade 3-4, % 6 5 - LDL-cholesterol grade 3-4, % 3 4 Median change in eGFR CG, mL/min - 7.8 - 9.6 0.01 Median % change in urine albumine:creatinine ratio - 0.3 + 5.2 0.25 Median % change in urine retinol binding protein:creatinine ratio + 21.2 + 22.1 0.91 Median % change in urine beta-2-microglobulin:creatinine ratio - 30.8 - 29.4 0.96 Bone DXA: mean % change in BMD between D0 and W96 BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) p Spine, % - 0.71 - 0.22 0.14 Hip, % - 1.13 - 1.26 0.59 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63

Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Mean changes in fasting lipids at W96, mg/dL Total cholesterol: HDL-cholesterol Ratio p = 0.003 0.5 -0.5 -1 3.7 -0.2 - 0.1 Total cholesterol LDL- cholesterol HDL- Triglycerides p = 0.002 p < 0.001 p = 0.17 p = 0.28 15 10 20 30 87,9 8 17 7 4 5 6 Mean baseline value, mg/dL 162 159 101 42 96 93 BIC/FTC/TAF DTG/ABC/3TC % of patients on lipid-lowering agents at baseline 3.8 % 2.2 % % of patients initiating lipid-lowering agents during study 4.1% GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63

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 96 results Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W96 by snapshot algorithm 87.9% of patients on BIC/F/TAF and 89.8% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL 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 Decrease in eGFR was significantly higher on DTG/ABC/3TC Increase in total-cholesterol and LDL-cholesterol was significantly higher on BIC/F/TAF, but the proportion of participants initiating lipid-lowering agents was not different between arms GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63 14