ARV-trial.com Switch to E/C/F/TAF GS-US-292-0112 Study 1

GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Design Open-label W24 W96 HIV+ ≥ 18 years Undetectable HIV-1 RNA ≥ 6 months HIV-1 RNA < 50 c/mL at screening Estimated creatinine clearance (Cockroft-Gault) 30-69 mL/min, stable in past 3 months CD4 ≥ 50/mm3 No resistance to EVG, TDF or FTC No HBV or HCV co-infection N = 242 Switch to E/C/F/TAF Co-formulated EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg (E/C/F/TAF) qd with food Endpoints Primary: change from baseline at W24 in estimated glomerular filtration rate by various formulas: Cockroft-Gault, CKD-EPI-cystatin C, CKD-EPI-creatinine Secondary: eGFR at W48 and W96, measured GFR, renal and bone biomarkers, hip and spine BMD (DXA), adverse events, virologic control GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7

Baseline characteristics ARV-trial.com GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Baseline characteristics Baseline eGFR < 50 mL/min N = 80 ≥ 50 mL/min N = 162 Median age, years 59 58 Female 26% 18% Race : black 19% HIV-1 RNA < 50 c/mL 98% CD4 cell count (/mm3), median 622 635 eGFR, median Cockroft-Gault, mL/min CKD-EPI, creatinine, mL/min/1.73 m2 CKD-EPI, cystatin C, mL/min/1.73 m2 43 45 57 60 77 Dipstick proteinuria : grade 1 or 2 44% 27% Urine protein:creatinine (UPCR) ≥ 200 mg/g 56% 35% Urine albumin:creatinine (UACR) ≥ 30 mg/g 64% 42% Pre-switch TDF use 58% 69% Hypertension 50% 34% Diabetes 15% 13% GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7 3

Estimated GFR (mL/min): Median change from Baseline to Week 24 GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Estimated GFR (mL/min): Median change from Baseline to Week 24 eGFRCG mL/min eGFRCKD-EPI Cr mL/min/1.73m2 eGFRCKD-EPI cys C mL/min/1.73m2 < 50 mL/min ≥ 50 mL/min Total -0.4 +1.2 - 0.9 -1.8 + 0.3 -2.2 +3.8 - 5 No clinically appreciable change in estimated creatinine clearance In 32 patients, GFR was measured by iohexol clearance: actual GFR was not affected over 24 weeks of treatment for the whole group, subgroups with baseline eGFRCG < 50 vs ≥ 50, or with or without TDF prior to switch GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7

Proteinuria: median value (mg/g) at baseline and W48 GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Proteinuria: median value (mg/g) at baseline and W48 Total* TDF* Non-TDF† Baseline Week 48 3 477 1 563 200 189 1 600 1 525 161 160 1 200 109 120 801 800 105 80 85 78 399 41 400 40 29 228 18 197 214 207 221 10 10 14 166 151 UPCR UACR RBP:Cr b-2-m:Cr Tubular Proteins *All Total and TDF changes statistically significant; †all non-TDF changes not statistically significant. GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7

Clinically significant proteinuria and albuminuria: baseline and W48 GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Clinically significant proteinuria and albuminuria: baseline and W48 Proteinuria (UPCR) Albuminuria (UACR) BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 Total eGFR < 50 mL/min eGFR ≥ 50 mL/min Total eGFR < 50 mL/min eGFR ≥ 50 mL/min GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7

BMD: mean change (%, SD) from baseline to W48 GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment BMD: mean change (%, SD) from baseline to W48 TDF Non-TDF Total Spine Hip 4 4 2.95* 2.29* 2 2 1.85* 1.47* 0.99 0.70 -2 -2 Baseline N = 236 W24 N = 226 W48 N = 214 Baseline N = 236 W24 N = 225 W48 N = 216 Spine Hip *p < 0.05 by two-sided Wilcoxon signed-rank test 6 % 4 % BMD change at week 48 37 % > 3 % gain 37 % Gain or loss < 3 % 59 % > 3 % loss 72 % GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7

ARV-trial.com GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Adverse events Most common adverse events Diarrhea 11% Upper respiratory tract infection 9% Arthralgia 9% Bronchitis 8% Osteopenia 8% Nausea 8% Headache 7% Pain in extremity 7% Back pain 7% Dizziness 6% Fatigue 6% Renal cyst 6% Cough 6% Adverse events leading to study drug discontinuation, N = 8 (3%), 2/8 for decreased GFR (both patients with hypertension) Fractures, N = 6, all related to mechanical trauma GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7 8

ARV-trial.com GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Fasting lipid changes Decrease in patients who used non-TDF-containing regimens prior to switching to E/C/F/TAF Increase in those using TDF-containing regimens prior to E/C/F/TAF Pharmacokinetics EVG and COBI: in the range of historical data in patients without renal impairment FTC: higher than historical data in patients without renal impairment, higher in patients with eGFR < 50 mL/min vs ≥ 50 mL/min TAF: consistent with historical data in patients without renal impairment TFV: higher than historical data in patients without renal impairment, but well below the TFV exposures from TDF-containing regimens Efficacy at W48 HIV-1 RNA < 50 c/mL: 92% Virologic failure: 1% (N = 3) GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7 9

ARV-trial.com GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment Conclusion In virologically suppressed HIV-infected subjects with renal impairment, switch to E/C/F/TAF was associated with minimal change in eGFR Proteinuria and albuminuria significantly improved Bone mineral density significantly improved in patients receiving TDF-containing regimens prior to switching to E/C/F/TAF Virologic success was maintained in 92% of patients These data support the efficacy and safety of once daily E/C/F/TAF in HIV-1 infected patients with mild (eGFR 50-69 mL/min) or moderate (eGFR 30-49 mL/min) renal impairment without dose adjustment GS-US-292-0112 Pozniak A. JAIDS 2016;71:530-7 10