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

GS-US-380-1844 Study: Switch to BIC/FTC/TAF Design Randomisation 1 : 1 Double-blind W48 N = 282 BIC/FTC/TAF 50/200/25 mg QD + DTG/ABC/3TC placebo HIV+ ≥ 18 years On DTG, ABC and 3TC HIV RNA < 50 c/mL ≥ 3 months eGFR (Cockroft-Gault) > 50 mL/min No active HBV infection BIC/FTC/TAF DTG/ABC/3TC 50/600/300 mg QD + BIC/FTC/TAF placebo Open-label extension N = 281 Endpoints 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-380-1844 Molina JM. CROI 2018, Abs. 22

GS-US-380-1844 Study: Switch to BIC/FTC/TAF Baseline characteristics BIC/FTC/TAF N = 282 DTG/ABC/3TC N = 281 Median age, years 47 45 Female, % 12 10 Ethnicity: white / black / hispanic, % 73 / 21 / 16 73 / 22 / 19 CD4 cell count (/mm3), median 732 661 eGFR (Cockroft-Gault), mL/min, median 101 GS-US-380-1844 Molina JM. CROI 2018, Abs. 22

GS-US-380-1844 Study: Switch to BIC/FTC/TAF Virologic outcome at W48 BIC/FTC/TAF (N = 282) DTG/ABC/3TC (N = 281) Difference : 0.7% (95.002% CI : - 1.0 to 2.8) 1.1 0.4 93.6 5.3 95.0 4.6 HIV RNA < 50 c/mL No virologic data 20 40 60 80 100 % HIV RNA ≥ 50 c/mL No emergence of resistance in either group GS-US-380-1844 Molina JM. CROI 2018, Abs. 22

Adverse events between D0 and W48, % GS-US-380-1844 Study: Switch to BIC/FTC/TAF Adverse events between D0 and W48, % BIC/FTC/TAF N = 282 DTG/ABC/3TC N = 281 Discontinuation for adverse event 6 (2.1%) * 2 (0.7%) ** Adverse event in ≥ 5% of either arm, % Upper respiratory tract infection Nasopharyngitis Headache Diarrhea Arthralgia Insomnia 10 7 7 9 7 3 10 8 7 5 4 5 Any study-drug related adverse event 23 (8.2%) 44 (15.7%) p = 0.01 Study drug-related adverse event in ≥ 1%, % Abnormal dreams Flatulence Nausea Fatigue 3 < 1 < 1 2 1 * Headache (N = 2), vomiting (N = 1), cerebrovascular accident (N = 1), abnormal dreams (N = 1), suicidal ideation (N = 1) ; ** headache (N = 1), pruritus (N = 1) GS-US-380-1844 Molina JM. CROI 2018, Abs. 22

Grade 3 or 4 laboratory abnormalities, N (%) GS-US-380-1844 Study: Switch to BIC/FTC/TAF Grade 3 or 4 laboratory abnormalities, N (%) BIC/FTC/TAF N = 282 DTG/ABC/3TC N = 281 Any 47 (17) 32 (11) Abnormality in ≥ 2% of either arm LDL-cholesterol Amylase ALT CK Fasting hyperglycemia 14 (5) 7 (2) * 6 (2) ** 6 (2) *** 6 (2) 13 (5) 2 (< 1) * All elevations transient and not associated with pancreatitis : lipase normal in 4/7 ** Acute HCV infection (N = 3), acute HAV infection (N = 1), alcohol (N = 1), NASH (N = 1) *** No case of rhabdomyolysis GS-US-380-1844 Molina JM. CROI 2018, Abs. 22

GS-US-380-1844 Study: Switch to BIC/FTC/TAF DTG/ABC/3TC Median percent change in quantitative proteinuria at W48 Median change in fasting lipids (mg/dL) at week 48 10 20 30 40 14 % 9 29 21 17 Total cholesterol p = 0.77 LDL cholesterol p = 0.42 HDL cholesterol p = 0.13 Triglycerides p = 0.028 Total cholesterol: HDL-chol. p = 0.56 Mean % change in bone mineral density UACR: urine albumin:creatinine ratio RBP: retinol-binding protein β-2-m: beta-2 microglobulin Spine Hip 2 1 24 48 256 244 233 262 253 0.69 0.42 p = 0.33 2 1 24 48 256 246 229 265 253 242 0.16 0.30 p = 0.47 Median change in eGFRCG at W48: - 4.3 mL/min BIC/FTC/TAF vs + 0.2 mL/min DTG/ABC/3TC (p < 0.001) n n GS-US-380-1844 Molina JM. CROI 2018, Abs. 22

GS-US-380-1844 Study: Switch to BIC/FTC/TAF Conclusion Switching to BIC/FTC/TAF was non-inferior to remaining on DTG/ABC/3TC, at W48 No treatment emergent resistance Discontinuation for adverse event was rare: 2% on BIC/FTC/TAF and 1% on DTG/ABC/3TC at W48 Study drug-related adverse events occurred with significantly higher frequency in DTG/ABC/3TC arm Increased grade 3-4 amylase was seen in 2% of BIC/FTC/TAF and no patient on DTG/ABC/3TC The lipid, bone and renal parameters of switching to BIC/FTC/TAF were comparable to remaining on DTG/ABC/3TC through 48 weeks GS-US-380-1844 Molina JM. CROI 2018, Abs. 22