Switch ABC/3TC to TAF/FTC ARV-trial.com Switch ABC/3TC to TAF/FTC GS-US-1717 Study 1

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC Randomisation 1 : 1 Double-blind Design W48 W96 TAF/FTC * + continuation 3rd agent + ABC/3TC placebo HIV+ adults On ABC/3TC + 3rd agent ≥ 6 months HIV-1 RNA < 50 c/mL ≥ 6 months Any CD4 Creatinine clearance ≥ 50 mL/min N = 280 ABC/3TC + continuation 3rd agent + TAF/FTC placebo N = 276 * TAF/FTC : 100/200 mg when coadministered with ATV boosted, DRV boosted or LPV/r ; 25/200 mg when co-administered with NNRTI, RAL, DTG or MVC Objective Primary endpoint: non-inferiority of TAF/FTC at W48: % HIV-1 RNA < 50 c/mL by ITT, snapshot analysis ; lower limit of the 95% CI for the difference = - 10%, 90% power GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC Baseline characteristics and patient disposition TAF/FTC N = 280 ABC/3TC N = 276 Median age, years 52 Female, % 14 22 Race : white / black, % 73 / 23 72 / 24 CD4/mm3, median 654 700 Median duration on ABC/3TC, years 8 Third agent, % NNRTI Boosted PI INI 51 30 19 53 30 16 Discontinuation by W48, N (%) For lack of efficacy, N For adverse event, N Withdrew consent / Lost to follow-up, N Investigator decision, N Non compliance / Protocol violation, N Death, N 31 (11) 1 12 10 / 3 3 1 / 0 18 (7) 9 6 / 0 0 / 2 GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC 88 Efficacy at W48 (ITT, snapshot) Per protocol analysis TAF/FTC (N = 253) ABC/3TC (N = 248) HIV RNA < 50 c/mL at W48 TAF/FTC : 99.1% ABC/3TC : 99.1% Difference : 0.0% (95% CI: -2.5 to 2.3) Difference (95% CI) : 0.8% (- 1.5 to 3.3) HIV RNA < 50 c/mL > 50 c/mL No virologic data 2 1 9 6 93 90 20 40 60 80 100 Difference : - 3.0% (95%CI : - 8.2 to 2.0) % Emergence of resistance, N TAF/FTC ABC/3TC Genotype at virologic failure * 4 1 Emergence of resistance NRTI : K65K/R PI : M46I + I50L + N88S 1 0 * Confirmed HIV RNA > 50 c/mL or unconfirmed > 400 c/mL at last visit GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC ARV-trial.com GS-US-1717 Study: Switch ABC/3TC to TAF/FTC Adverse events TAF/FTC ABC/3TC Adverse events ≥ 5% in either arm, % Nasopharyngitis Upper respiratory tract infection Diarrhea Headache Arthralgia Cough Fatigue Back pain Urinary tract infection 13 9 9 7 6 6 5 5 2 11 12 9 5 7 5 4 6 5 Adverse events leading to drug discontinuation, N (%) 12 (4) * 9 (3) ** Grade 3-4 laboratory abnormalities ≥ 2% in either arm, % LDL-cholesterol Hyperbilirubinemia Creakine kinase Amylase Hypercholesterolemia 22 5 5 3 3 2 18 5 3 4 2 2 * Considered related to study drug (n = 8) : abdominal distension + myalgia, nausea + vomiting + dehydration, nausea + feeling jittery + decrease appetite, anxiety, Brugada syndrome, increased creatinine, burning sensation + headache + paresthesia, vision blurred + visual field defect + eye pain ; not related to study drug : cough, tuberculosis, sudden cardiac death, neutropenia ** Considered related to study drug (n = 8) : affective disorder, panic attack, depression + bone pain + arthralgia, dermatitis + pruritus, rash + pruritus, diarrhea, myalgia + dysesthesia, tinnitus + dry mouth + dyspnea ; not related to study drug : depression + suicide attempt GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71 5

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC 89 Median changes in creatinine clearance (Q1, Q3), mL/min TAF/FTC ABC/3TC 12 24 36 48 -10 10 1.3 mL/min - 1.1 mL/min p = 0.05 Weeks No difference between groups in changes at W48: in renal biomarkers (urine RBP:creatinine and B2M:creatinine ratios) in bone mineral density (hip and lumbar spine) Median changes in fasting lipids at W48, mg/dL TAF/FTC ABC/3TC -1 3 2 4 -2 -10 10 Total cholesterol LDL- cholesterol HDL- cholesterol Triglycerides p = 0.18 p = 0.54 p = 0.48 p < 0.001 GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71

GS-US-1717 Study: Switch ABC/3TC to TAF/FTC ARV-trial.com GS-US-1717 Study: Switch ABC/3TC to TAF/FTC Conclusion Switch from ABC/3TC to TAF/FTC was non inferior to ABC/3TC in maintaining virologic suppression in combination with a variety of third agents No differences of TAF/FTC vs ABC/3TC in Renal biomarkers Bone mineral density Fasting lipids In virologically suppressed patients with creatinine clearance > 50 mL/min, TAF/FTC provides an alternative backbone to ABC/3TC with similar effects on kidney and bone GS-US-1717 Winston A, Lancet HIV.2018 ; 5:e162-71 7