1. Comparison of INSTI vs EFV  STARTMRK  GS-US-236-0102  SINGLE

2. Sax PE. Lancet 2012;379:2439-48 GS-US-236-0102  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 EFV/FTC/TDF placebo EFV/FTC/TDFQD 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-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD N = 352 N = 348 W48W192

3. EVG/c/FTC/TDF N = 348 EFV/FTC/TDF N = 352 Mean age, years38 Female12%10% HIV RNA (log 10 c/mL), median4.754.78 HIV RNA >100,000 c/mL34%33% CD4 cell count (/mm 3 ), median376383 CD4 < 200 per mm 3 12%14% Hepatitis B / hepatitis C coinfection3% / 5%3% / 4% Discontinuation by W4810.6%13.1% For lack of efficacyN = 5N = 4 For adverse eventN = 12N = 18 Lost to follow-upN =10N = 12 Non-complianceN = 3N = 6 Discontinuation by W9615.2%17.3% Discontinuation by W14418.4%23% Baseline characteristics and patient disposition Sax PE. Lancet 2012;379:2439-48 ; Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 GS-US-236-0102 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

4. Mean CD4/mm 3 increase at W48 : + 239 (EVG/c/FTC/TDF) vs + 206 (EFV/FTC/TDF), P = 0.009 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 Sax PE. Lancet 2012;379:2439-48 GS-US-236-0102 HIV RNA < 50 c/mL 25 50 100 75 87.6 84.1 % Adjusted difference (95% CI)= 3.6% (- 1.6 ; 8.8) 94.9 96.0 Primary analysis Adjusted difference (95% CI)= -1.0 % (- 4.4 ; 2.4) ITT, snapshotPer protocol EVCG/c/FTC/TDF EFV/FTC/TDF 0 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

5. Response to treatment at week 96 and week 144 Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 GS-236-0103 HIV RNA < 50 c/mL at week 96 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 EVCG/c/FTC/TDF EFV/FTC/TDF 0 HIV RNA < 50 c/mL at week 144 25 50 100 75 80.2 75.3 % Adjusted difference (95% CI)= 4.9 % (- 1.3; 11.1) Adjusted difference (95% CI)= 4.1 % (- 1.9 ; 10.0) ITT, snapshotITT, M = F 82.2 78.1 EVCG/c/FTC/TDF EFV/FTC/TDF 0 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

6. Secondary efficacy outcomes at week 144 EVG/c/FTC/TDFEFV/FTC/TDF HIV-1 RNA < 50 c/mL in patients with baseline HIV-1 RNA < 100,000 c/mL 81.7%74.2% Adjusted difference: 7.6% ; 95% CI : 0.1% ; 15.1% HIV-1 RNA 100,000 c/mL 77.1%77.6% Mean CD4/mm 3 increase+ 321+ 300 Sax PE. Lancet 2012;379:2439-48 ; Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 EVG/c/FTC/TDFEFV/FTC/TDFP Creatinine (  mol/l) 13 (5 ; 20)1 (-6 ; 8)< 0.001 eGFR (mL/min)- 14.3 (-24.2 ; -4.3)- 3.0 (-11.2 ; 8.2)< 0.001 Median (IQR) change in creatinine and eGFR at week 48 GS-236-0103 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

7.  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 = 348 EFV/FTC/TDF N = 352 Analysed for the development of resistance14 (4%)17 (5%) Emergent primary integrase mutations7*- Emergent reverse transcriptase resistance88 M184V/I K65R NNRTI mutation 83-83- 2 8** * Q148R, N = 1, N155H, N = 1, E92Q, N = 7, T66I, N = 1 ; ** K103N, N = 7, K101E, N = 3, V108I, N = 1, Y188F/H/K, N = 1, G190A, N = 1 Sax PE. Lancet 2012;379:2439-48 GS-US-236-0102 Resistance data at week 48 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

8. EVG/c/FTC/TDF N = 348 EFV/FTC/TDF N = 352 Total D0- W48 W48- W96 W96- W144 Total D0- W48 W48- W96 W96- W144 Emergent resistance, n1082014824 INSTI resistance9720- E92Q7700 N155H3120 Q148R1100 T66I1100 NRTI resistance108204211 M184V/I108204211 K65R43103210 NNRTI resistance-14824 K103N13724 GS-236-0103 Resistance data at week 144 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 ; White KL. Antiviral Therapy 2015, ePub ahead of print

9. EVG/c/FTC/TDFEFV/ FTC/TDF Total at week 4813 (4%)18 (5%) Nausea10 General Disorder13 Liver injury10 Drug hypersensitivity01 Infection12 Neoplasm11 Neuropsychiatric disorder49 Creatinine increased20 Renal failure20 Fanconi syndrome10 Dyspnoea02 Rash, drug eruption04 Other03 Total at week 9617 (4.9%)24 (6.8%) Total at week 14421 (6.0%)26 (7.4%) Treatment-emergent adverse events leading to premature discontinuation of study drugs GS-US-236-0102 Sax PE. Lancet 2012;379:2439-48 ; Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

10. EVG/c/FTC/TDFEFV/FTC/TDFP Diarrhoea80 (23 %)66 (19 %)- Nausea72 (21 %)48 (14 %)0.016 Upper respiratory tract infection48 (14 %)38 (11 %)- Dizziness23 (7%)86 (24%)< 0.001 Headache49 (14 %)34 (10 %)- Abnormal dreams53 (15 %)95 (27 %)< 0.001 Insomnia30 (9%)49 (14 %)0.031 Depression33 (9%)39 (11%)- Rash22 (6%)43 (12%)0.009  Adverse events occurring in > 10% of patients in either group (W48) EVG/c/FTC/TDFEFV/FTC/TDFP Total cholesterol (mmol/L), median change0.250.49< 0.001 LDL cholesterol (mmol/L), median change0.260.44 0.001 HDL cholesterol (mmol/L), median change0.130.200.001 Graded ALT abnormality15 %34 %< 0.001 Graded AST abnormality18 %31 %< 0.001  Laboratory test results at week 48 Sax PE. Lancet 2012;379:2439-48 GS-US-236-0102 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

11. GS-US-236-0102  Discontinuation for renal event –EVG/c/FTC/TDF 5 between D0 and W48: 4/5 patients developed signs of tubular toxicity (hypophosphataemia, and/or glycosuria, and/or proteinuria 2 between W48 and W96 : decreased GFR, renal failure 1 between W96 and W144 : creatinine increase, without tubulopathy –EFV/FTC/TDF No discontinuation  Discontinuation for neuropsychiatric event –EVG/c/FTC/TDF 3 before W48, none after –EFV/FTC/TDF 6 before W48, 4between W48 and W96, none between W96 and W144  Discontinuation for rash –EVG/c/FTC/TDF No discontinuation –EFV/FTC/TDF 4 before W48, none between W48 and W144 Sax PE. Lancet 2012;379:2439-48 ; Zolopa A, JAIDS 2013;63:96-100 ; Wohl DA, JAIDS 2014;65:e118-121 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD

12.  Summary of week 48 results –EVG/c/FTC/TDF QD is virologically non inferior to EFV/FTC/TDF –Similar virologic reponse of the 2 regimens in different subgroups of patients, including those high HIV RNA at enrolment –Discontinuation because of adverse events : 4 % vs 5 % –Development of major resistance mutations occurred in 8 patients on EVG/c/FTC/TDF : 7 with integrase mutations, 8 with NRTI mutations 8 patients on EFV/FTC/TDF : 8 with NNRTI mutations, 2 with NRTI mutations –Incidence of adverse events was similar except for neuropsychiatric adverse events and rash (more frequent with EFV/FTC/TDF), and nausea (more frequent with EVG/c/FTC/TDF) –Median increases in creatinine with decreases in estimated glomerular filtration rate more pronounced with EVG/c/FTC/TDF –Five patients on EVG/c/FTC/TDF discontinued for renal events  Week 144 results –D urable efficacy of EVG/c/FTC/TDF, with no new renal safety signal and a longer-term safety profile that is differentiated from EFV/FTC/TDF Sax PE. Lancet 2012;379:2439-48 ; Wohl DA, JAIDS 2014;65:e118-121 GS-US-236-0102 Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD