1. Comparison of PI vs PI  ATV/r vs DRV/rATADAR

2. ATV/r 300/100 mg + TDF/FTC qd N = 91 N = 89 DRV/r 800/100 mg + TDF/FTC qd  Design Randomisation 1: 1 Open-label  Objective –Primary Endpoint : mean change in total cholesterol at W24 (ITT analysis) –90 patients per arm needed to detect a difference ≥ 21 mg/dL between arms in total cholesterol change, power 80%, 5% bilateral significance –Secondary endpoints : mean change in other lipid parameters, insulin resistance, total bilirubin, eGFR (MDRD equation), CD4 and CD8 cell counts, HIV RNA, discontinuation for AEs ATADAR Martinez E. HIV Medicine 2014;15:330-8 ≥ 18 years Antiretroviral naïve HIV RNA > 1,000 c/mL No diabetes, BMI < 30 kg/m 2 No current use of drugs affecting lipid or glucose metabolism W24W96 ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC

3. Baseline characteristics and disposition ATV/r + TDF/FTC, N = 90DRV/r + TDF/FTC, N = 88 Age, years3537 Female13%11% HIV RNA log 10 c/mL4.8 CD4/mm 3 328341 Total cholesterol, mg/dL158 LDL-cholesterol, mg/dL9798 HDL-cholesterol, mg/dL39 Total cholesterol:HDL-cholesterol ratio4.54.4 Triglycerides, mg/dL106108 HOMA-IR2.42.5 Total bilirubin, mg/dL0.540.58 eGFR (MDRD), mL/min/1.73 m 2 110106 Discontinued at W24N = 8 (9%) Adverse event53 Withdrew consent / lost to follow-up1 / 20 / 5 Data expressed as mean ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. HIV Medicine 2014;15:330-8

4. Virological efficacy and overall tolerability at W24 ATV/r + TDF/FTC, N = 90 DRV/r + TDF/FTC, N = 88 Confirmed HIV RNA > 50 c/mL, n78 Any AE, all grade, %63.362.5 Grade 3-4 AEs, %22.48.0 (p< 0.01) Bilirubin elevations, n170 Jaundice3/170 AEs leading to study drug discontinuation, n (%)5 (5.6%)3 (3.4%) Jaundice, n30 Rash, n12 Suicide attempt, n10 Gastrointestinal symptoms, n01 ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. HIV Medicine 2014;15:330-8

5. Lipid changes from baseline to W24 ATV/r + TDF/FTC N = 90 DRV/r + TDF/FTC N = 88 p Total cholesterol, mg/dL + 7.26 ± 26.76+ 11.47 ± 25.85 0.29 LDL-cholesterol, mg/dL - 2.14 ± 21.45+ 3.14 ± 21.97 0.12 HDL-cholesterol, mg/dL + 5.50 ± 10.36+ 3.88 ± 8.42 0.26 Total:HDL-cholesterol ratio - 1.16 ± 6.38- 0.14 ± 0.86 0.07 Triglycerides+ 16.29 ± 61.76+ 18.40 ± 64.240.83 No participant was prescribed lipid-lowering agents or other drugs potentially affecting plasma lipids ATV/r + TDF/FTC N = 90 DRV/r + TDF/FTC N = 88 p HOMA-IR + 0.08 ± 0.24+ 0.03 ± 0.34 0.38 Total bilirubin, mg/dL + 1.85 ± 1.30- 0.02 ± 0.30 < 0.01 eGFR, mL/min/1.73m 2 - 6.89 / 22.16- 5.64 ± 14.540.67 Other laboratory changes from baseline to W24 ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. HIV Medicine 2014;15:330-8

6.  Metabolic sub-study in 86 participants (ATV/r = 45, DRV/r = 41) – LDL subfraction phenotype and Lp-PLA2 at W48, Framingham risk score change. Patients assessed at W48 : 40/45 and 37/41 – LDL subfraction phenotype : predominance of the more favorable phenotype at baseline (around 75% of participants) – ATV/r : increase in cholesterol content in small and dense LDL particles, associated with coronary artery disease risk (p = 0.015) at W48 – DRV/r : increase in LDL size (p = 0.017) and large LDL particles (p = 0.008) (improved atherogenic properties) at W48 – No change in total Lp-PLA2 activity and no shift in its relative distribution in LDL or HDL particles at W48, with no differences between arms – Framingham score very low at baseline (1%) with no changes at W48 – Insulin increased only in the ATV/r group (p = 0.017), but HOMA-IR showed no changes in either arm at W48 – BMI increased in the ATV/r arm (+1.01 kg/m 2 at W48, p = 0.004) [p= 0.06 vs DRV/r] – Waist increased in the DRV/r arm (+ 3 cm at W48, p < 0.001) [p = 0.027 vs ATV/r] ATADAR Saumoy M. J AntimicrobChemother 2015;70:1130-8 ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC

7.  W96 results (efficacy and resistance) ATV/r + TDF/FTC N = 90 DRV/r + TDF/FTC N = 88 Discontinuation by W9621 (23%)17 (19%) For AE / virologic failure7 / 25 / 2 % free of treatment failure62%70%95% CI : - 0.6 to 21.6 % free of virologic failure (VF) 79%85%95% CI : - 0.5 to 17.6 Resistance testing ♯ 6/17 VF5/13 VF PI mutations detected (none major)4*/64**/5 * V45M ; E35D + K43K/N + D60E + I93L ; A71V + E35D + M36I + I62V + I93L ; L24I/V ** I15V ; E35D + L63P ; E35D + L63P ; I13V + M36I/M + I62I/V + L63H/Q ♯ no baseline resistance test ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. CID 2015;60:811-20

8.  W96 results (safety) ATV/r + TDF/FTC, N = 72DRV/r + TDF/FTC, N = 74p Serious AEs26%8%0.002 Grade 3-4 AEs44%14%< 0.0001 AE leading to discontinuation7.8%5.7%0.25 ATV/rDRV/r p Total cholesterol, mg/dL+ 11.31+ 14.63 All non significant LDL-cholesterol, mg/dL+ 1.86+ 8.22 HDL-cholesterol, mg/dL+ 4.8+ 4.9 Total:HDL-cholesterol ratio- 0.82- 0.29 Triglycerides+ 38.89+ 15.65 eGFR (MDRD), mL/min/1.73 m 2 - 8.63-7.27 Overall safety Lipid and other laboratory changes, mean ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. CID 2015;60:811-20

9. ATV/r + TDF/FTC, N = 78DRV/r + TDF/FTC, N = 80p BMI, kg/m 2 + 1.25+ 0.670.13 Body fat, g+ 3373+ 10960.009 Body fat-free mass, g+ 894+ 6610.71 Limb fat, g+ 1235-1680.007 Trunk fat, g+ 1566+ 5410.10 Subcutaneous abdominal adipose tissue, cm 2 + 38.8+ 14.90.036 Visceral adipose tissue, cm 2 + 38.8+ 30.10.47 Total abdominal adipose tissue, cm 2 + 77.3+ 45.10.06 Bone mineral content, g- 79.8- 80.20.99 Changes in body composition (DXA and abdominal CT-scan) at W96 Data expressed as mean In the ATV/r arm : significant correlations between changes in HOMA-IR and changes in BMI, body fat, and SAT In the DRV/arm : no correlations between HOMA-IR changes and changes in BMI and body fat parameters ATADAR ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC Martinez E. CID 2015;60:811-20

10.  Conclusion – No major differences between ATV/r + TDF/FTC and DRV/r + TDF/FTC in efficacy, clinically relevant side effects, or plasma cholesterol fractions, over 96 weeks – However, ATV/r led to higher triglycerides and more total and subcutaneous fat than DRV/r – Fat gains with ATV/r were associated with insulin resistance – In contrast with what occurred in the ATV/r arm, the LDL subfraction phenotype improved with DRV/r at W48. This difference was associated with a lower impact on plasma triglycerides with DRV/r – Most Grade 3-4 AE were due to hyperbilirubinemia, in the ATV/r arm ATADAR Martinez E. CID 2015;60:811-20 ; Saumoy M. J AntimicrobChemother 2015;70:1130-8 ATADAR Study: ATV/r + TDF/FTC vs DRV/r + TDF/FTC