1. Comparison of INSTI vs PI  FLAMINGO  GS-236-0103  ACTG A5257  WAVES

2. DeJesus E. Lancet 2012;379:2429-38  Design  Objective –Non inferiority of EVG/c/FTC/TDF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided 95% CI for the difference = -12%, 95% power) EVG/c/FTC/TDF 150/150/200/300 mg QD ATV/r + TDF/FTC placebo ATV/r 300/100 mg + TDF/FTC QD EVG/c/FTC/TDF placebo Randomisation* 1 : 1 Double-blind > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count eGFR> 70 mL/min *Randomisation was stratified by HIV RNA ( 100,000 c/mL) at screening Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD N = 355 N = 353 W48W192 GS-236-0103

3. EVG/c/FTC/TDF N = 353 ATV/r + FTC/TDF N = 355 Mean age, years3839 Female8%11% HIV RNA (log 10 c/mL), mean 4.8±0.614.8±0.62 HIV RNA > 100,000 c/mL42%40% CD4 cell count (/mm 3 ), median351366 CD4 < 200 per mm 3 15%11% Hepatitis B / hepatitis C coinfection1% / 5%2% / 3% Discontinuation by W489.3%11.3% For lack of efficacyN = 4N = 1 For adverse eventN = 13N = 18 Lost to follow-upN = 7 Non-complianceN = 5 Discontinuation by W9614%15% Baseline characteristics and patient disposition DeJesus E. Lancet 2012;379:2429-38 ; Rockstroh JK, JAIDS 2013;62:483-6 GS-236-0103 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

4. Response to treatment at week 48 DeJesus E. Lancet 2012;379:2429-38 GS-236-0103 Mean CD4/mm 3 increase at W48 : + 207 (EVG/c/FTC/TDF) vs + 211 (ATV/r + FTC/TDF) Viral suppression was high in both treatment arms, for various subgroups including patients with HIV RNA > 100 000 c/mL at baseline 25 50 100 75 89.5 86.8 Adjusted difference (95% CI)= 3.0 % (- 1.9; 7.8) 97.5 97.7 Adjusted difference (95% CI)= = -0.1 % (- 2.6; 2.4) ITT, snapshotPer protocol EVG/c/FTC/TDF ATV/r + FTC/TDF HIV RNA < 50 c/mL Primary analysis % 0 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

5. DeJesus E. Lancet 2012;379:2429-38 GS-236-0103 ARN VIH < 50 c/ml Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

6. Response to treatment at week 96 and week 144 Rockstroh JK, JAIDS 2013;62:483-6 ; Clumeck N, JAIDS 2014;65:e121-4 GS-236-0103 25 50 100 75 83.3 82.3 % Adjusted difference (95% CI)= 1.1 % (- 4.5 ; 6.7) 86.7 85.4 Adjusted difference (95% CI)= 1.4 % (- 3.8 ; 6.5) ITT, snapshotITT, M = F EVG/c/FTC/TDF ATV/r + FTC/TDF HIV RNA < 50 c/mL at week 96 0 25 50 100 75 77.6 74.6 % Adjusted difference (95% CI)= 3.1 % (- 3.2; 9.4) Adjusted difference (95% CI)= 2.3 % (- 3.6 ; 8.2) ITT, snapshotITT, M = F 81.0 78.9 HIV RNA < 50 c/mL at week 144 EVG/c/FTC/TDF ATV/r + FTC/TDF 0 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

7. Response to treatment at week 144 EVG/c/FTC/TDFATV/r + FTC/TDF Virologic failure7.9 %7.3 % Mean CD4/mm 3 increase+ 280+ 293 No treatment difference in virologic success for various subgroups, including patients with HIV RNA > 100,000 c/mL at baseline, except for adherence > 95 % (favoring EVG/c/FTC/TDF) EVG/c/FTC/TDFATV/r + FTC/TDF W48W96W144W48W96W144 Lumbar spine- 2.63 %- 1.96 %- 1.43%*- 3.33 %- 3.54 %-3.68%* Hip- 3.06 %- 3.16 %- 2.83%- 3.88 %- 4.19 %-3.77% * p = 0.018 DeJesus E. Lancet 2012;379:2429-38 ; Rockstroh JK, JAIDS 2013;62:483-6 ; Clumeck N, JAIDS 2014;65:e121-4 GS-236-0103 Mean decrease in bone mineral density Secondary outcomes Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

8.  Virologic failure definition –Suboptimal virologic response : 2 consecutive visits with HIV RNA ≥ 50 c/mL and <1 log 10 c/mL below baseline at or after week 8 –Virologic rebound (2 consecutive visits with HIV RNA either ≥ 400 c/mL after achieving HIV RNA 1 log 10 c/mL increase from nadir) –HIV RNA ≥ 400 c/mL at their last visit (at or after week 8)  Criteria for resistance testing –Virological failure or HIV RNA > 400 c/mL at study discontinuation (at or after W8 and taking study drug) EVG/c/FTC/TDF N = 353 ATV/r + FTC/TDF N = 355 Analysed for the development of resistance12 (3.4%)8 (2.3%) Emergent primary integrase mutations4*, **- Emergent reverse transcriptase resistance40 M184V K65R 4141 ---- Emergent primary protease mutation-0 * Q148R, N = 2, N155H, N = 1, T66I + E92Q + N155H, N = 1 ; ** 1 had also M184V + K65R and 2 M184V DeJesus E. Lancet 2012;379:2429-38 GS-236-0103 Resistance data at week 48 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

9. EVG/c/FTC/TDF N = 353 ATV/r + FTC/TDF N = 355 Total D0- W48 W48- W96 W96- W144 Total D0- W48 W48- W96 W96- W144 Emergent resistance, n85*12**2002 INSTI resistance6411- E92Q2110 N155H2200 Q148R2200 T66I1100 T97A1001 NRTI resistance74122002 M184V/I74122 K65R11000 Protease mutation-0 Resistance data at week 144 Rockstroh JK, JAIDS 2013 62:483-6 ; Clumeck N, JAIDS 2014;65:e121-4 * INSTI + NRTI resistance, N = 3, ** INSTI + NRTI resistance, N = 1 GS-236-0103 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

10. EVG/c/FTC/TDFATV/r + FTC/TDF Total at week 4813 (3.7%)18 (5.1%) Ocular icterus/Jaundice0 / 04 / 2 Gastro-intestinal disorder45 General disorder32 Drug hypersensitivity10 Infection12 Overdose01 Aminotransferase increased20 Creatinine increased10 Nephropathy toxic01 Limb discomfort or rhabdomyloysis20 Neoplasm11 Neuropsychiatric disorder43 Rash, drug eruption24 Other30 Total at week 9615 (4.2%)21 (5.9%) Total at week 14421 (5.9%)30 (8.5%) DeJesus E. Lancet 2012;379:2429-38 ; Rockstroh JK, JAIDS 2013;62:483-6 ; Clumeck N, JAIDS 2014;65:e121-4 GS-236-0103  Treatment-emergent adverse events leading to premature discontinuation of study drugs Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

11. EVG/c/FTC/TDFATV/r + FTC/TDF Diarrhoea77 (22%)97 (27%) Nausea70 (20%)69 (19%) Upper respiratory tract infection54 (15%)58 (16%) Headache53 (15%)44 (12%) Fatigue50 (14%)45 (13%) Ocular icterus2 (1%)51 (14%)  Treatment-emergent adverse events occurring in > 10% of patients in either group (week 48) DeJesus E. Lancet 2012;379:2429-38 EVG/c/FTC/TDFATV/r + FTC/TDFP Triglycerides (mg/dL), median change0.090.260.006 Creatinine (  mo/L), median change (IQR) 11 (5 ; 18)7 (1 ; 15)< 0.001 eGFR (mL/min), median change (IQR)- 12.7 (- 21.8 ; 4.3)- 9.5 (- 17.9 ; 0.2)< 0.001 Graded ALT abnormality15.3%21.6%0.041 Severe/life threatening bilirubin abnormality0.6%58.2%< 0.001  Laboratory test results at week 48 GS-236-0103 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

12. Discontinuations due to renal event EVG/c/FTC/TDFATV/r + FTC/TDF W48W96W144W48W96W144 Discontinuation for renal event212116 Proximal renal tubulopathy000003 DeJesus E. Lancet 2012;379:2429-38 ; Rockstroh JK, JAIDS 2013; 62:483-6 ; Clumeck N, JAIDS 2014;65:e121-4 GS-236-0103 Median change in serum creatinine (  mol/L) concentration from baseline EVG/c/FTC/TDF ATV/r + FTC/TDF -5 5 20 10 Weeks -10 0 15 0248121624324048 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD

13.  Summary (W48 results) –EVG/c/FTC/TDFQD was virologically non inferior to ATV/r + FTC/TDF –Similar virologic reponse of the 2 regimens in different subgroups of patients, including those with high HIV RNA at enrolment –Discontinuation because of adverse events was lower with EVG/c/FTC/TDF : 3.7% vs 5.1% –Development of major resistance mutations occurred in 5 patients on EVG/c/FTC/TDF : 4 with integrase mutations (3/4 had also NRTI mutations), 1 with only RT mutation (M184V) none on ATV/r + FTC/TDF –Incidence of adverse events was similar except for jaundice/icterus –Median increases in creatinine with accompanying decreases in estimated glomerular filtration rate occurred in both study groups by week 2 generally stabilized by week 8 and did not change up to week 48 median change : + 11 μmol/L vs + 7 μmol/L ; P < 0.001 DeJesus E. Lancet 2012;379:2429-38 GS-236-0103 Study GS-236-0103: EVG/c/FTC/TDF QD vs ATV/r + FTC/TDF QD