1. Comparison of RTV vs Cobi  GS-US-216-0114

2. Gallant JE. JID 2013;208:32-9 GS-US-216-0114  Design  Objective –Non inferiority of COBI compared with RTV at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower limit for the 95% CI for the difference = -12%, 95% power) COBI + RTV placebo + ATV 300 mg + FTC/TDF QD COBI placebo + RTV + ATV 300 mg + FTC/TDF QD Randomisation* 1 : 1 Double-blind > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count eGFR > 70 mL/min Sensitivity to ATV, FTC And TDF on genotype * Randomisation was stratified by HIV RNA ( 100,000 c/mL) at screening Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF N = 348 N = 344 W48W192

3. COBI + ATV + FTC/TDF N = 344 RTV + ATV + FTC/TDF N = 348 Mean age, years3738 Female17%18% HIV RNA (log 10 c/mL), median4.784.84 HIV RNA > 100,000 c/mL38.4%41.1% CD4 cell count (/mm 3 ), mean353351 CD4 < 200 per mm 3 12%16% Hepatitis B / hepatitis C coinfection5% / 6%3% / 5% Discontinuation by W4817%11% For lack of efficacyN = 2N = 0 For adverse eventN = 25 Lost to follow-upN = 11N = 4 Non-complianceN = 43 Baseline characteristics and patient disposition Gallant JE. JID 2013;208:32-9 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF

4. HIV RNA < 50 c/mL Mean CD4/mm 3 increase at W48 : + 213 COBI vs + 219 RTV Response to treatment at week 48 Viral suppression was high in both treatment arms, for various subgroups, including patients with HIV RNA > 100,000 c/mL at baseline Gallant JE. JID 2013;208:32-9 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF 25 50 100 75 % Adjusted difference (95% CI) = -2.2%( - 7.4 ; 3.0) 98.0 Primary analysis Adjusted difference (95% CI) = -0.1 % ( - 2.5 ; 2.3) COBI + ATV + FTC/TDF RTV + ATV + FTC/TDF ITT, snapshotPer protocol 98.0 85.2 87.4 0

5. Gallant JE. JAIDS 2015;69:338-40 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF Response to treatment at week 144 (ITT, snapshot) Virologic successVirologic failureNo data HIV RNA < 50 c/mL W48W144W48W144W48W144 0 20 40 60 80 100 85 87 72 74 6 4 8 5 9 9 2021 % COBI + ATV + FTC/TDF RTV + ATV + FTC/TDF Adjusted difference (95% CI) = -2.1%( -8.7 ; 4.5)

6.  Criteria for resistance testing : confirmed HIV-1 RNA load rebound of ≥ 400 c/mL or not obtaining HIV RNA < 400 c/mL by or after week 8 COBI + ATV + FTC/TDF N = 344 RTV + ATV + FTC/TDF N = 348 At W48W48-W144At W48W48-W144 Analysed for the development of resistance12 (3.5%)9 (2.6%)12 (3.4%)7 (2.1%) Available data10-12- Emergent reverse transcriptase resistance2201 M184V211 V118I010 Emergent mutations to protease inhibitors0000 Gallant JE. JID 2013;208:32-9 ; Gallant JE. JAIDS 2015;69:338-40 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF Resistance data up to week 144

7. COBI + ATV + FTC/TDFRTV + ATV + FTC/TDFp Jaundice20.9%15.5%0.076 Scleral icterus17.7%18.4%- Nausea17.7%16.4%- Diarrhea15.4%20.4%0.093 Headache11.0%15.5%0.093 Nasopharyngitis10.8%15.2%0.09 Hyperbiluribinemia11.3%9.8%  Adverse events occurring in > 10% of patients in either group (W48) Gallant JE. JID 2013;208:32-9 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF COBI + ATV + FTC/TDFRTV + ATV + FTC/TDF Median increase of creatinine (mg/dL) at W48+ 0.13+ 0.09 (P < 0.001) Grade 3-4 hyperbilirubinemia65.3%56.6% Grade 3-4 elevation of ALT / AST3.2% / 2.9%2.0% / 2.0% Increase in total cholesterol (mg/dL) at week 48+ 5 + 9 (NS) Increase in triglycerides (mg/dL) at week 48+ 19 + 32 (NS)  Laboratory abnormalities at W48

8.  Adverse events leading to discontinuation of study drug COBI + ATV + FTC/TDF N = 344 RTV + ATV + FTC/TDF N = 348 W48W48-W144W48W48-W144 Total number of patients (%)25 (7.3%)925 (7.2%)8 Scleral icterus8441 Jaundice9170 Hyperbilirubinemia1021 Rash1000 Allergic dermatitis2000 Renal AEs6456 Gallant JE. JID 2013;208:32-9 ; Gallant JE. JAIDS 2015;69:338-40 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF  Proximal renal tubulopathy –7 in each group –In 5 of the 7 patients in the COBI group and 6 of the 7 patients in the RTV group, PRT occurred after week 48

9. 20 10 0 -10 -20 -30 -40 BL24487296120144 -15.1 -13.7 -12.9 -9.1 -8.3 -7.5 Week GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF Change in eGFR (mL/min), median [IQR]Change in serum creatinine (mg/dL), median [IQR] 0.4 0.3 0.2 0.1 0.0 -0.1 -0.2 0.13 BL24487296120144 0.07 0.080.09 0.13 0.12 Week Serum Creatinine and eGFR Gallant JE. JAIDS 2015;69:338-40 COBI + ATV + FTC/TDF RTV + ATV + FTC/TDF

10.  No difference in TC:HDL ratio changes between arms (- 0.3 vs -0.2) Median change in fasting lipids at week 144 (mg/dL) GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF Gallant JE. JAIDS 2015;69:338-40 Total cholesterolLDL-c HDL-c Triglycerides p = 0.35p = 0.11 p = 0.49 20 15 10 5 0 12 16 9 14 7 5 11 15 COBI + ATV + FTC/TDF RTV + ATV + FTC/TDF

11.  Summary –COBI was non inferior to RTV in combination with ATV plus FTC/TDF up to week 144 Both regimens achieved high rates of virologic success –Safety and tolerability profiles of the 2 regimens were comparable –Once-daily COBI is a safe and effective pharmaco-enhancer of the protease inhibitor ATV –Renal safety was comparable between treatment arms Discontinuation due to renal events was 2.9% in the COBI group and 3.2% in the RTV group at W144 Proximal renal tubulopathy occurred in 7 vs 7 patients (2.0%) A small, but significantly higher with COBI, increase in creatinine was seen in both groups, as early as week 2, with peak at week 8, and stabilization through 144 weeks Gallant JE. JID 2013;208:32-9 ; Gallant JE. JAIDS 2015;69:338-40 GS-US-216-0114 Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF