Switch to BIC/FTC/TAF GS-US-380-1878 GS-US-380-1844 GS-US-380-1961

GS-US-380-1878 Study: Switch to BIC/FTC/TAF Design Randomisation 1 : 1 Open-label W48 N = 290 BIC/FTC/TAF 50/200/25 mg QD HIV+ ≥ 18 years On boosted ATV or DRV + 2 NRTI (ABC/3TC or FTC/TDF) HIV RNA < 50 c/mL ≥ 6 months eGFR (Cockroft-Gault) > 50 mL/min Continuation of baseline ART N = 287 Endpoint Primary: proportion of patients with HIV RNA ≥ 50 c/mL at W48 (ITT, snapshot) ; non-inferiority if upper margin of a two-sided 95.002% CI for the difference = 4% GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

GS-US-380-1878 Study: Switch to BIC/FTC/TAF Baseline characteristics and patient disposition BIC/FTC/TAF N = 290 Continuation ART N = 287 Median age, years 48 47 Female, % 16 18 Ethnicity: white / black / hispanic, % 52 / 27 / 21 59 / 25 / 16 CD4 cell count (/mm3), median 617 626 HBV / HCV co-infection, % 8 / 5 6 / 5 eGFR (Cockroft-Gault), mL/min, median 107 105 Discontinuation by W48, N (%) For adverse event, N For lack of efficacy, N Investigator discretion, N Consent withdrawal, N Loss to follow-up, N Non-compliance, N Protocol violation, N Death, N 16 (5.5%) 2 1 9 26 (9.1%) 14 3 5 GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

GS-US-380-1878 Study: Switch to BIC/FTC/TAF Virologic outcome at W48 BIC/FTC/TAF (N = 290) Continuation ART (N = 287) Difference : 0% (95.002% CI: - 2.5 to 2.5) 1.7 92.1 6.2 88.9 9.4 HIV RNA < 50 c/mL No virologic data 20 40 60 80 100 Difference : 3.3% (95.002% CI : - 1.6 to 8.2) % HIV RNA ≥ 50 c/mL Patients analysed for resistance: 1 BIC/FTC/TAF vs 3 Continuation ART Emergence of resistance : 0/1 vs 1/3 (L74V in a patient on ABC/3TC + DRV/r) GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

Adverse events between D0 and W48, % Fracture/acute kidney injury GS-US-380-1878 Study: Switch to BIC/FTC/TAF Adverse events between D0 and W48, % BIC/FTC/TAF N = 290 Continuation ART N = 287 Discontinuation for adverse event, N 2 Rash ; Schizophrenia 1 Fracture/acute kidney injury Adverse event in ≥ 5% of either arm, % Headache Diarrhea Nasopharyngitis Upper respiratory tract infection Back pain Arthralgia 12 8 7 7 5 4 4 6 12 8 6 5 Grade 3-4 laboratory abnormalities, % LDL-cholesterol Amylase Glycosuria ALT Total bilirubin Total cholesterol Hematuria 3.9 2.1 2.1 2.1 0.7 0.7 1.7 4.0 2.1 1.1 1.4 15.4 2.2 2.7 GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

GS-US-380-1878 Study: Switch to BIC/FTC/TAF Median percent change in quantitative proteinuria at W48 Baseline FTC/TDF-containing regimen Baseline ABC/3TC-containing regimen BIC/FTC/TAF Continuation ART RBP:Cr β-2-m:Cr UACR % 40 30 20 10 -10 -20 -30 -40 -50 -2.1 9.9 -17.7 -40.3 34.9 31.6 RBP:Cr β-2-m:Cr UACR % 40 30 20 10 -10 -20 -30 -40 -50 4.2 1.1 5.4 -19.5 7.3 25.8 UACR: urine albumin:creatinine ratio ; RBP: retinol-binding protein ; β-2-m: beta-2 microglobulin Median change in eGFRCG at W48: - 4.3 mL/min BIC/FTC/TAF vs + 0.2 mL/min continuation ART (p < 0.001) GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

Total Cholesterol: HDL GS-US-380-1878 Study: Switch to BIC/FTC/TAF Median Fasting Lipid Changes at Week 48 (mg/dL) BIC/FTC/TAF Continuation ART Total Cholesterol LDL Cholesterol Triglycerides HDL Cholesterol p = 0.32 p = 0.47 p = 0.13 p = 0.002 30 20 10 -10 -20 -30 1 5 3 -6 4 Total Cholesterol: HDL p = 0.033 -0,2 1,5 1,0 0,5 0,0 -0,5 -1,0 -1,5 Taking lipid lowering agents at baseline: B/F/TAF : 16.2%, Continuation ART : 15.7%, p = 0.91 Initiated lipid lowering agents during the study: B/F/TAF : 2.8%, Continuation ART: 3.5%, p = 0.64 GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56

GS-US-380-1878 Study: Switch to BIC/FTC/TAF Conclusions Switching to BIC/FTC/TAF was non-inferior to remaining on a boosted protease inhibitor + 2 NRTI 1.7% of subjects in each arm had HIV-1 RNA ≥ 50 c/mL through 48 weeks 92.1% of subjects treated with BIC/FTC/TAF maintained virologic suppression vs 88.9% in the continuation arm No treatment emergent resistance in patients who switched to BIC/FTC/TAF 1 subject who continued DRV/r + ABC/3TC developed resistance mutation to ABC BIC/FTC/TAF was well tolerated Adverse events were comparable between arms at week 48 mild headache was reported more with BIC/FTC/TAF but was mostly transient and low grade Less than 1% of patients discontinued due to an adverse event in both arms No difference in grade 3 or 4 laboratory abnormalities between arms, except for more total bilirubin abnormalities in continuation arm due to ATV use Statistically significant improvements in triglycerides and total cholesterol:HDL ratio in subjects who switched to BIC/FTC/TAF GS-US-380-1878 Daar ES. Lancet 2018;5:e347-56