1. Phase 2 of new ARVs TAF (TFV prodrug) - Study 292-0102 - Study 299-0102

2.  Design  Objective –Primary endpoint : non inferiority of D/C/F/TAF at W24: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2 sided 95% CI for the difference = -12%) –Secondary endpoints : HIV RNA < 50 c/mL at W48, safety, tolerability D/C/F/TAF STR 800/150/200/10 mg QD DRV 400 mg x 2 + COBI + F/TDF placebos QD DRV 400 mg x 2 + COBI 150 mg + F/TDF 200/300 mg QD D/C/F/TAF STR QD placebo Randomisation* 2 : 1 Double-blind Adults ≥ 18 years ARV-naïve HIV RNA > 5,000 c/mL CD4 cell count > 50/mm 3 eGFR ≥ 70 mL/min Sensitive to DRV, FTC and TDF * Randomisation was stratified by HIV RNA ( 100,000 c/mL) and race (black or nonblack) Study GS-US-299-0102: D/C/F/TAF QD STR vs DRV + COBI + F/TDF QD N = 50 N = 100 W24W48 Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102 D = darunavir ; C = cobicistat ; F = FTC

3. D/C/F/TAF N = 103 DRV + COBI + F/TDF N = 50 Median age, years3136 Female8%6% Black35%34% HIV RNA (log 10 c/mL), median4.74.6 HIV RNA > 100,000 c/mL22%14% CD4 cell count (/mm 3 ), median368433 CD4 < 200 per mm 3 10.7%20% eGFR (Cockroft-Gault), mL/min, median116110 Discontinuation by W4819 (18%)8 (16%) For investigator’s discretion10 For adverse event22 Lost to follow-up / Withdrew consent10 / 44 / 2 Non-compliance20 Baseline characteristics and patient disposition Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102

4. Response to treatment HIV RNA < 50 c/mL, ITT, snapshot analysis D/C/F/TAFDRV + COBI + F/TDF 171/ 196 174/ 195 96/ 112 104/ 117 703 /753 680/ 750 25 50 100 75 74.8 74.0 % Adjusted difference (95% CI) = 3.3% (- 11.4 ; 18.1) 76.7 84.0 Primary analysis, W24 (Overall) 0 W48 Adjusted difference (95% CI) = -6.2% (- 19.9 ; 7.4) D/C/F/TAF DRV + COBI + F/TDF Virologic failure16%12% No data8%4% Outcome at W48 D/C/F/TAF DRV + COBI + F/TDF W24+ 186+ 139 W48+ 231+ 212 p : not significant CD4/mm 3 response Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102

5. Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD D/C/F/TAF N = 103 DRV + COBI + F/TDF N = 50 Virologic failure6 (5.8%)2 (4%) No emergence of resistance to TDF, FTC or DRV  Criteria for resistance testing –Confirmed virologic failure : 2 consecutive HIV RNA > 50 c/mL and an HIV RNA > 400 c/mL at or after W8 –Second, confirmatory, sample, tested for resistance Resistance data at week 48 Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102

6. D/C/F/TAFDRV + COBI + F/TDF Grade 3-4 AE6.8%8.0% AEs (all grades) in ≥ 10% of patients in either group Diarrhea21.4%26% Upper respiratory tract infection15.5%14% Fatigue13.6%18% Nausea12.6%10% Rash11.7%8% Flatulence4.9%12% Pain in extremity7.8%10% Vitamin D deficiency1.9%10% Vomiting3.9%10% Serious AEs4.9%4.0% AE leading to discontinuation N = 2 Rash; Substance dependance N = 2 Worsening of diarrhea ; Proximal renal tubulopathy Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Adverse events by W48 Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102

7. Renal outcome at W48 D/C/F/TAFDRV + COBI + F/TDFP Mean (95% CI) change from baseline in creatinine, mg/dL + 0.06 (0.04 - 0.08)+ 0.09 (0.05 - 0.14)0.053 Median decrease in eGFR (Cockroft-Gault), mL/min -2.9-10.60.017 Median change in urine retinol binding protein/creatinine ratio, mg/g + 9%+ 54%0.003 Median change in urine beta-2 microglobulin/creatinine ratio, mg/g -42%+2.3%0.002 Median change in urine albumin/creatinine ratio, mg/g -13.1% -22.6% 0.17 Median change in urine protein/creatinine ratio, mg/g -8.22%-27.52% 0.19 Median change in fractional excretion of phosphates + 2.4%+ 1.8%ns Emergent dipstick proteinuria32%34%ns Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102

8. Mean percentage change from baseline in bone mineral density (DEXA) Total hipLumbar spine -0.53 -0.84 -2.09 -3.82 -5 -4 -3 -2 0 P < 0.001 W24W48 -1.09 -1.57 -3.82 -3.62 -4 -3 -2 0 P < 0.001P = 0.003 W24W48 Bone sub-study outcome at W48 D/C/F/TAFDRV + COBI + F/TDFP BMD decline > 3% in hip18.3%61.7%< 0.001 BMD decline > 3% in lumbar spine32.5%55.3%0.002 P1NP (bone formation) increase+ 4.7%+ 52.5%< 0.001 CTx (bone resorption) increase+ 23.2%+ 74.4%< 0.001 P1NP : pro-collagen Type 1 N-terminal propeptide ; CTx : C-terminal telopeptide Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102 D/C/F/TAF DRV + COBI + F/TDF

9. Median change in fasting metabolic parameters at Week 48 D/C/F/TAFDRV + COBI + F/TDFP Total cholesterol, mg/dL+ 40+ 5< 0.001 LDL-cholesterol, mg/dL+ 26+ 4< 0.001 HDL-cholesterol, mg/dL+ 7+ 30.009 Total cholesterol:HDL-cholesterol ratio0.0-0.20.15 Triglycerides, mg/dL+ 29-50.007 Serum glucose, mg/dL+ 5+ 70.33 Initiation of lipid lowering agent by W486.8%8% Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015, epub ahead of print GS-US-299-0102

10. Study GS-US-299-0102: D/C/F/TAF QD vs DRV + COBI + F/TDF QD Mills A, JAIDS 2015,epub ahead of print GS-US-299-0102  Conclusion –D/C/F/TAF had significantly improved renal and bone safety parameters than DRV + COBI + F/TDF in antiretroviral-naïve, HIV-1 infected subjects : Less proteinuria Less change in hip and spine BMD –Study limitations Small sample size Each participant had to take 5 tablets (double-blind) not optimal for patient’s adherence and retention in the study Few women enrolled –This D/C/F/TAF STR offers a promising option for initial HIV treatment, with The high barrier to resistance of DRV And the potential for improved long-term renal and bone safety with TAF