Comparison of NRTI combinations ARV-trial.com Comparison of NRTI combinations ZDV/3TC vs TDF + FTC Study 934 ABC/3TC vs TDF/FTC HEAT Study ACTG A5202 Study ASSERT Study FTC/TDF vs FTC/TAF Studies GS-US-292-0104 and GS-US-292-0111 AMBER Study

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD ARV-trial.com AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Design Randomisation* 1:1 Double-blind W48 W96 N = 362 D/C/F/TAF QD D/C + F/TDF placebo HIV+ Adults ARV-naïve HIV RNA > 1 000 c/mL CD4 cell count > 50/mm3 eGFR > 50 mL/min D/C/F/TAF QD N = 363 D/C + F/TDF QD D/C/F/TAF placebo D/C/F/TAF QD * Randomisation was stratified by HIV RNA (< or ≥ 100 000 c/mL) and CD4 cell count (< or ≥ 200/mm3) Objective Non inferiority of E/C/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 95% CI for the difference = -10%) AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD ARV-trial.com AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Baseline characteristics and patient disposition D/C/F/TAF N = 362 D/C + F/TDF N = 363 Median age, years 34 Female, % 12.2 11.3 HIV RNA (log10 c/mL), median 4.4 4.6 HIV RNA > 100 000 c/mL, % 16.6 19.3 CD4 cell count (/mm3), median 461.5 440 CD4 < 200 per mm3, % 6.1 8 eGFR (Cockroft-Gault), mL/min, median 119 118 Discontinuation by W48, N (%) 23 (6.4) 28 (7.7) For adverse event, N 15 Lost to follow-up / Withdrew consent, N 5 / 4 5 / 6 Physician decision 3 Non-compliance, N 1 Death, N 1 (follow-up phase) Other reasons, N 2 AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD 66 Virologic outcome at W48 (ITT, snapshot) D/C/F/TAF (N = 362) D/C + F/TDF (N = 363) 91.4 4.4 4.1 88.4 3.3 8.3 20 40 60 80 100 HIV RNA < 50 c/mL ≥ 50 c/mL No data % - 1.6 Adjusted difference, % (95% CI) Favours D/C/F/TAF Favours D/C + F/TDF Resistance analysis Virologic failures with paired genotypes (baseline and failure with HIV RNA ≥ 400 c/mL), N = 9 [7 D/C/F/TAF + 2 D/C + F + TDF]: 1 patient with emergence of M184I/V (D/C/F/TAF) AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD 66 Virologic outcome at W48 by baseline strata (ITT, snapshot) D/C/F/TAF (N = 362) D/C + F/TDF (N = 363) 91.7 90.4 20 40 60 80 100 CD4 ≥ 200/mm3 % 92.6 88.6 72.7 86.2 CD4 < 200/mm3 HIV RNA ≤ 100 000 c/mL > 100 000 c/mL 89.8 80.0 N 303 293 340 59 70 334 22 29 Difference (95% CI) 1.3 (-3.4 to 6.1) 9.8 (- 3.3 to 22.5) 4 (- 0.4 to 8.6) - 13.5 (- 37.8 to 9.6) AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Mean (SE) change from baseline in eGFR (mL/min/1.73m2) based on serum creatinine and CKD-EPI formula based on serum cystatin and CKD-EPI formula D/C/F/TAF (N = 340) D/C + F/TDF (N = 330) D/C/F/TAF (N = 337) D/C + F/TDF (N = 329) 4 8 12 16 20 24 28 32 36 40 44 48 Weeks ** -4 -8 -12 -4 -8 -12 4 8 12 16 20 24 28 32 36 40 44 48 Weeks * p < 0.0001 * ** p = 0.0001 AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Mean (SE) changes (mg/g) in proteinuria at W48 D/C/F/TAF Urinary protein: creatinine D/C + F/TDF Urinary albumin: creatinine BL 66.23 (3.66) 77.67 (6.51) BL 11.38 (1.57) 17.92 (5.07) 10 p = 0.033 -22.42 -10.34 -40 -30 -20 -10 p = 0.003 -2.45 -0.58 5 -5 -10 -25 Retinol binding protein: creatinine β-2-microglobulin: creatinine p < 0.0001 401.12 16.84 200 400 600 p < 0.0001 -100.58 837.63 1 500 500 -500 BL 110.66 (7.12) 186.73 (74.66) BL 248.45 (40.36) 379.54 (176.11) AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Mean (SE) % changes in bone mineral density at W48 Spine Hip D/C/F/TAF (N = 96) D/C + F/TDF (N = 85) D/C/F/TAF (N = 96) D/C + F/TDF (N = 85) p < 0.0001 p = 0.00* 1 2 -1 -2 -3 -4 -1.3 -3.4 Weeks 24 48 p < 0.0001 0.3 -1.7 -2.7 0.2 1 2 -1 -2 -3 -4 Weeks 24 48 D/C/F/TAF D/C + F/TDF ≥ 3% decrease 27.1% 41.2% 12.5% 44.7% ≥ 3% increase 4.7% 2.4% AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Median lipid values (mg/dL) TC:HDL-C ratio D/C/F/TAF baseline D/C + F/TDF baseline D/C/F/TAF W48 D/C + F/TDF W48 250 196 4.0 3.9 200 3.8 3.8 4 172 163 162 150 3 123 116 112 97 101 96 97 95 100 2 48 42 42 44 50 1 Total cholesterol LDL-C HDL-C Triglycerides TC:HDL-C ratio AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD ARV-trial.com AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Adverse events through W48, % D/C/F/TAF N = 362 D/C + F/TDF N = 363 Grade 3-4 adverse event 5.2 6.1 Serious adverse event 4.7 5.8 Discontinuation due to adverse event 1.9 * 4.4 ** Death Adverse event possibly related to study drug Diarrhea Rash Nausea 34.8 8.6 6.1 5.5 41.6 11.0 3.9 9.9 Diarrhea, any grade 19.6 18.2 * rash (N = 6); diarrhea (N = 1) ** rash/erythema (N = 7), diarrhea (N = 1), toxic skin eruption (N = 2), Stevens Johnson syndrome (N = 1), bone marrow oedema (N = 1), increased beta-2 macroglobulin (N = 1), arthralgia (N = 1), neoplasm (N = 2) No grade 3 or 4 laboratory abnormalities in ≥ 5% of patients in either arm No discontinuation of D/C/F/TAF for bone, renal or CNS adverse event AMBER Eron J, EACS 2017, Abs. PS8/2

AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD ARV-trial.com AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD Conclusion Through Week 48, D/C/F/TAF resulted in high virologic suppression in treatment-naïve patients (91.4% ; FDA Snapshot) that was non-inferior to DRV/C + F/TDF (88.4%) No development of DRV, primary PI or TDF/TAF RAMs One patient developed M184I/V (D/C/F/TAF arm) Few serious adverse events, grade 3/4 adverse events, or adverse events- related discontinuations No discontinuations due to bone, renal, or CNS adverse events Bone, renal and lipid safety consistent with known profiles of TAF and cobicistat AMBER Eron J, EACS 2017, Abs. PS8/2 11