Switching to Tenofovir Alafenamide (TAF) Regimen in Virologically Suppressed Adults

Switching From a Tenofovir Disoproxil Fumarate (TDF)-Based Regimen to a Tenofovir Alafenamide (TAF)-Based Regimen: Data in Virologically Suppressed Adults Through 48 Weeks of Treatment Anthony Mills,1Jaime Andrade-Villanueva,2Giovanni DiPerri,3Jan Van Lunzen,4Ellen Koenig,5Richard Elion,6Matthias Cavassini,7Jose Valdez-Madruga,8Jason Brunetta,9 David Shamblaw,10Edwin DeJesus,11Andrew Plummer,12YaPei Liu,12and Scott McCallister,12 on behalf of the Gilead GS-US-292-0109 Study Team 1Southern California Men s Medical Group, Los Angeles, CA, USA; 2Hospital Civil de Guadalajara, Mexico; 3Amedeo di Savoia Hospital, Turin, Italy; 4Universit tsklinikum Hamburg-Eppendorf, Hamburg, Germany; 5Instituto Dominicano de Estudios Virol gicos, Santo Domingo, Dominican Republic; 6Whitman-Walker Health, Washington, DC, USA; 7Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland; 8Centro de Refer ncia e Treinamento em DST/AIDS, Sao Paolo, Brazil; 9Maple Leaf Research, Toronto, Canada; 10La Playa Medical Group, San Diego, CA, USA; 11Orlando Immunology Center, Orlando, FL, USA; 12Gilead Sciences, Inc., Foster City, CA, USA IAS 2015, Vancouver

Disclosures Dr. Anthony Mills is a study investigator for study GS-US-292-0109. He also serves as an advisory board member for Gilead and has received travel expenses related to this. Dr. Mills reports grants, personal fees and non-financial support from Gilead, during the conduct of the study. He has also received grants and personal fees from ViiV, grants and personal fees from Merck, grants from BMS, grants and personal fees from Janssen, outside the submitted work. 2

GS-US-292-0109 Switch to E/C/F/TAF in Virologically Suppressed Adults Primary Endpoint HIV-1 RNA <50 c/mL Randomized (2:1), active-controlled, open-label study 96 Week 0 48 E/C/F/TDF (n=459) n=959 Switch to E/C/F/TAF EFV/FTC/TDF (n=376) Virologically Suppressed Adults Continue TDF-Based Regimen Boosted* ATV + FTC/TDF n=477 (n=601) All patients HIV-1 RNA <50 copies/mL for 96 weeks on stable TDF-based regimen Estimated GFR >50 mL/min E/C/F/TAF = EVG 150 mg, COBI 150 mg, FTC 200 mg, TAF 10 mg E/C/F/TDF = EVG 150 mg, COBI 150 mg, FTC 200 mg, TDF 300 mg *Boosted by RTV or COBI 3

GS-US-292-0109 Baseline Characteristics E/C/F/TAF n=959 41 TDF-Based Regimen n=477 40 Median age, years Female, % 11 11 Race, % White 68 66 Black or African descent 18 21 Hispanic/Latino ethnicity 26 17 Median CD4 count, cells/mm3 675 662 Patients with <200 cells/mm3, % 0.5 0.8 Median estimated GFR, mL/min* 106 108 Dipstick proteinuria, % Grade 1 8.5 9.2 Grade 2 0.4 0.6 *Cockcroft-Gault. 4

GS-US-292-0109 HIV-1 RNA <50 Copies/mL at Week 48 Treatment Difference (95% CI) Virologic Outcome E/C/F/TAF n=959 97 100 93 TDF-Based Regimen n=477 TDF Based E/C/F/TAF HIV-1 RNA <50 c/mL, % 80 60 4.1 40 1.6 6.7 20 6 2 1 1 0 Success Failure No Virologic Data 17 +12% 12% 0 n= 932 444 10 6 27 5

GS-US-292-0109 Virologic Outcome, Prior Treatment Regimens Primary Endpoint E/C/F/TAF TDF-Based Regimen p <0.001 97 100 93 Patients With HIV-1 RNA <50 c/mL, % 80 60 40 20 932 959 444 477 241 251 112 125 390 402 183 199 301 306 149 153 0 All Prior Regimens Prior Prior Boosted ATV + FTC/TDF Prior EFV/FTC/TDF E/C/F/TDF 95% CI = 1.6 6.7 0.5 12.1 0.4 8.7 6

GS-US-292-0109 Virologic Outcome, Prior Treatment Regimens Primary Endpoint E/C/F/TAF TDF-Based Regimen p <0.001 p=0.02 97 96 100 93 Patients With HIV-1 RNA <50 c/mL, % 90 80 60 40 20 932 959 444 477 241 251 112 125 390 402 183 199 301 306 149 153 0 All Prior Regimens Prior Prior Boosted ATV + FTC/TDF Prior EFV/FTC/TDF E/C/F/TDF 95% CI = 1.6 6.7 0.5 12.3 0.5 12.1 0.4 8.7 7

GS-US-292-0109 Virologic Outcome, Prior Treatment Regimens Primary Endpoint E/C/F/TAF TDF-Based Regimen p <0.001 p=0.02 p=0.02 97 97 96 100 93 92 Patients With HIV-1 RNA <50 c/mL, % 90 80 60 40 20 932 959 444 477 241 251 112 125 390 402 183 199 301 306 149 153 0 All Prior Regimens Prior Prior Boosted ATV + FTC/TDF Prior EFV/FTC/TDF E/C/F/TDF 95% CI = 1.6 6.7 0.5 12.3 0.9 9.2 0.4 8.7 8

GS-US-292-0109 Virologic Outcome, Prior Treatment Regimens Primary Endpoint E/C/F/TAF TDF-Based Regimen p <0.001 p=0.02 p=0.02 p=NS 98 97 97 97 96 100 93 92 Patients With HIV-1 RNA <50 c/mL, % 90 80 60 40 20 932 959 444 477 241 251 112 125 390 402 183 199 301 306 149 153 0 All Prior Regimens Prior Prior Boosted ATV + FTC/TDF Prior EFV/FTC/TDF E/C/F/TDF 95% CI = 1.6 6.7 0.5 12.3 0.9 9.2 -1.9 3.9 9

GS-US-292-0109 Virologic Outcome, Differences by Subgroup TDF-Based Regimen E/C/F/TAF Overall* <50* Age, y 50 Male* Sex Female Black Race Non-Black* <95% Adherence 95%* -12 -6 0 6 12 Treatment Difference in Participants with HIV-1 RNA <50 c/mL, % (95% CI) *Statistically significant difference favoring E/C/F/TAF treatment. 10

GS-US-292-0109 Grade 2 4 Lab Abnormalities E/C/F/TAF n=959 TDF-Based Regimen n=477 Patients, % Any abnormality Creatine kinase AST ALT Neutropenia Phosphate ( ) Uric acid ( ) Alkaline phosphatase Leukopenia Platelets Total bilirubin Hemoglobin Creatinine 25 10 5 5 4 31 10 7 5 3 3 1 <1 <1 <1 24 <1 <1 New Data TK 2 2 <1 <1 <1 <1 0 0 11

GS-US-292-0109 Fasting Lipid Results E/C/F/TAF Baseline Week 48 TDF-Based Regimen Baseline Week 48 5 250 204 4 200 Median Values (mg/dL) 3.8 185 3.7 182 181 3.6 3.6 3 150 130 125 116 120 114 113 116 116 2 100 52 1 50 49 50 49 0 0 Total Cholesterol p <0.001 LDL p <0.001 HDL p <0.001 p <0.001 p=0.004 Triglycerides TC:HDL Ratio Participants initiating lipid-modifying medications: E/C/F/TAF: 7.9%; TDF-based regimen: 5.9%. 12

GS-US-292-0109 Adverse Events >5% (All Grades) E/C/F/TAF n=959 TDF-Based Regimen n=477 Participants, % Upper respiratory tract infection 16 11 Diarrhea 10 9 Nasopharyngitis 9 8 Headache 7 4 Cough 7 5 Arthralgia 6 5 Bronchitis 6 5 Osteopenia 6 5 Syphilis 5 6 Insomnia 5 6 Sinusitis 5 5 Back pain 5 5 Nausea 5 3 13

GS-US-292-0109 AEs Leading to Discontinuation E/C/F/TAF n=959 TDF-Based Regimen n=477 Participants % 0.9 2.5 Acute renal failure Interstitial nephritis Chronic kidney disease Elevated serum creatinine Fanconi syndrome, mild jaundice Increased creatinine Nephretic colic (nephrolithiasis) Renal Events Depression Leg swelling, impaired concentration Memory loss, speech disturbance, lack of motivation Nausea, vomiting, headache Panic attack Reiter syndrome Suicide attempt Abnormal dreams Depression, insomnia, irritability Depression, insomnia, nightmares Elevated bilirubin Icterus (n=2) Increased forgetfulness All Other Events After cancer chemotherapy, participant hospitalized with neutropenia, sepsis, and multi-system organ failure Recurrent hematuria on treatment, subsequent off-treatment diagnosis of Hodgkin s Lymphoma 14

GS-US-292-0109 DXA Scan Results: Spine BMD Change From Baseline to Week 48 All Participants (N=1,369) Median % Change in BMD (Q1, Q3) 4 E/C/F/TAF 3 TDF-Based Regimen 2 1.79 1 p <0.001 0 -0.28 -1 -2 -3 Baseline Week 24 Week 48 Regardless of prior treatment regimen, differences between arms were statistically significant More than 2% difference between the arms at Week 48 15

GS-US-292-0109 DXA Scan Results: Hip BMD Change From Baseline to Week 48 All Participants (N=1,354) Median % Change in BMD (Q1, Q3) 3 E/C/F/TAF 2 TDF-Based Regimen 1.37 1 p <0.001 0 -0.26 -1 -2 Baseline Week 24 Week 48 Regardless of prior treatment regimen, differences between arms were statistically significant More than 1.6% difference between arms at Week 48 16

GS-US-292-0109 Change in Diagnosis of Osteopenia or Osteoporosis (Defined by T-Score) Normal Osteopenia Osteoporosis Spine 7.6 5.8 4.8 7.2 100 80 32 36 35 37 Patients, % 60 40 64 59 57 56 20 0 E/C/F/TAF Baseline E/C/F/TAF n=912 E/C/F/TAF Week 48 TDF TDF Baseline Week 48 Baseline TDF-Based Regimen n=457 Week 48 Regimen Baseline Regimen Week 48 Differences between E/C/F/TAF and TDF-based regimens were statistically significant (p <0.001) 17

GS-US-292-0109 Change in Diagnosis of Osteopenia or Osteoporosis (Defined by T-Score) Normal Osteopenia Osteoporosis Spine 7.6 5.8 4.8 7.2 100 80 32 36 35 37 Patients, % 60 40 64 59 57 56 20 0 E/C/F/TAF Baseline E/C/F/TAF n=912 E/C/F/TAF Week 48 TDF TDF Baseline Week 48 Baseline TDF-Based Regimen n=457 Week 48 Regimen Baseline Regimen Week 48 Differences between E/C/F/TAF and TDF-based regimens were statistically significant (p <0.001) 18

GS-US-292-0109 Change in Diagnosis of Osteopenia or Osteoporosis (Defined by T-Score) Normal Osteopenia Osteoporosis Spine Hip 7.6 5.8 4.8 2.1 7.2 1.3 0.7 0.7 100 100 26 31 32 32 80 80 32 36 35 37 Patients, % 60 60 40 40 73 69 67 66 64 59 57 56 20 20 0 0 E/C/F/TAF Baseline E/C/F/TAF n=912 E/C/F/TAF Week 48 TDF TDF E/C/F/TAF Baseline E/C/F/TAF Week 48 TDF Baseline TDF-Based Regimen n=452 TDF Week 48 Baseline Week 48 Baseline TDF-Based Regimen n=457 Week 48 Baseline Week 48 Regimen Baseline Regimen Week 48 Regimen Baseline Regimen Week 48 E/C/F/TAF n=902 Differences between E/C/F/TAF and TDF-based regimens were statistically significant (p <0.001) 19

GS-US-292-0109 Renal Safety Results Tubular Proteinuria UPCR UPCR UACR UACR RBP: Cr Ratio RBP:Cr B2MG: Cr Ratio -2-m:Cr E/C/F/TAF 30 TDF-Based Regimen 20 19 18 10 10 9 Median % Change 0 -10 -18 -21 -20 -33 -30 -40 Each difference between treatment arms was statistically significant (p <0.001). -52 -50 -60 Statistically significant improvements for participants who switched from either E/C/F/TDF or from boosted ATV + FTC/TDF Serum creatinine (p <0.001); eGFR (p <0.001) Fractional excretion of phosphate, FEPO4 (p=0.05); fractional excretion of uric acid, FEUA (p <0.001) Changes began by Week 2 and persisted to Week 48 UPCR: urine protein: creatinine ratio; UACR: urine albumin: creatinine ratio; RBP, retinol-binding protein; -2-m:Cr , beta-2 microglobulin. 20

Week 48 Conclusions Study GS-292-0109 is the largest randomized switch study conducted in HIV-positive virologically suppressed adults Participants who switched to E/C/F/TAF were significantly more likely to maintain virologic success Had significant improvements in spine and hip BMD Had significant reductions in osteopenia/osteoporosis Had significant improvements in proteinuria and other markers of renal function 21

Acknowledgments We extend our thanks to the participants, their partners and families, and all GS-US-292-0109 investigators. F Ajana, B Akil, H Albrecht, J Andrade Villanueva, J Angel, A Antinori, K Arast h, J Arribas L pez, D Baker, J Baril, N Bellos, P Benson, D Berger, L Bhatti, A Blaxhult, M Bloch, R Bolan, I Brar, U Bredeek, J Brunetta, J Burack, M Cavassini, P Chetchotisakd, A Clarke, N Clumeck, B Conway, P Cook, D Cooper, L Cotte, D Coulston, C Creticos, G Crofoot, F Cruickshank, E DeJesus, G Di Perri, M Doroana, R Dretler, J Durant, H Edelstein, G F tkenheuer, J Fehr, R Finlayson, J Flamm, H Furrer, F Garcia, J Gathe, J Gerstoft, S Gilroy, P Girard, J Goffard, D Goldstein, P Grant, P Greiger-Zanlungo, B Grinsztejn, R Grossberg, B Haas, C Hare, T Hawkins, P Hay, K Henry, A Hite, C Hoffmann, R Hsu, G Huhn, H J ger, T Jefferson, M Johnson, K Kasper, C Katlama, W Kern, S Kiertiburanakul, C Kinder, D Klein, E Koenig, M Kozal, T Kuberski, A LaMarca, A Lazzarin, R LeBlanc, C Lucasti, T Lutz, J Madruga, C Martorell, S Mauss, C Mayer, C McDonald, J McGowan, M McKellar, G McLeod, J McMahon, D Mildvan, A Mills, J Molina, R Moore, J Morales-Ramirez, G Moyle, O Munhoz Leite, D Murphy, R Nahass, H Olivet, C Orkin, A Paez, P Palmieri, D Parks, A Petroll, D Podzamczer Palter, R Pollard, D Prelutsky, A Rachlis, F Raffi, M Ramgopal, B Rashbaum, W Ratanasuwan, G Richmond, A Rieger, B Rijnders, G Rizzardini, W Robbins, A Roberts, J Rockstroh, A Rosengren, N Roth, P Ruane, K Ruxrungtham, M Saag, S Saavedra- Sanquirico, L Salazar, L Santiago, T Schmidt, B Schmied, S Schneider, A Scribner, S Segal-Maurer, M Sension, R Serr o, P Shalit, D Shamblaw, C Shikuma, J Slim, D Smith, M Sokol-Anderson, M Somero, T Souza, K Squires, D Stein, C Stephan, J Stephens, K Supparatpinyo, P Tebas, M Thompson, W Towner, J vaLunzen, T Vanig, P Viciana Fern ndez, G Voskuhl, S Walmsley, D Ward, M Wensley, D Wheeler, E Wilkins, T Wills, D Wohl, B Yangco, Y Yazdanpanah, B Young, C Zurawski This study was funded by Gilead Sciences, Inc. 22