Combined Primary Results of
Studies GS-US-292-0104 and GS-US-292-0111
David Wohl 1 , Anton Pozniak 2 , Melanie Thompson 3 , Edwin DeJesus 4 ,
Daniel Podzamczer 5 , Jean-Michel Molina 6 , Gordon Crofoot 7 ,
Christian Callebaut 8 , Hal Martin 8 , Scott McCallister 8
1 University of North Carolina, Chapel Hill, NC; 2 Chelsea and Westminster Hospital,
NHS Foundation Trust, London, UK; 3 AIDS Research Consortium of Atlanta, Atlanta, GA;
4 Orlando Immunology Center, Orlando, FL; 5 Hospital Universitari de Bellvitge, Barcelona,
Spain; 6 Hôpital Saint Louis, Paris, France; 7 Gordon Crofoot Research, Houston, TX;
8 Gilead Sciences, Foster City, CA
Abstract 113LB
CROI 2015, Seattle

 Dr. Wohl has served as an advisor to Gilead Sciences and Janssen, and the University of North Carolina Chapel Hill has received funding from Gilead Sciences and Merck
2

 Tenofovir disoproxil fumarate (TDF) is included in most recommended antiretroviral regimens, and although potent and generally well tolerated, has been associated with clinically significant renal and bone toxicity 1-3
 Relative to TDF 300 mg, tenofovir alafenamide (TAF) 25 mg has 90% lower circulating plasma TFV, while maintaining high antiviral activity 4
 In Phase 2, efficacy of elvitegravir, cobicistat, emtricitabine, and TAF
(E/C/F/TAF) was comparable to E/C/F/TDF, and demonstrated significant improvements in renal and bone safety 5
 We sought to confirm the efficacy of E/C/F/TAF in two fully powered clinical trials
1. DeJesus E, et al. Lancet 2012;379:2429-38; 2. Gallant JE, et al. J Infect Dis 2013;208:32-9; 3. Sax PE, et al. Lancet
2012;379:2439-48; 4. Ruane P, et al. J Acquir Immune Defic Syndr 2013; 63:449-55; 5. Sax PE, et al. J Acquir Immune
Defic Syndr 2014;67:52-8.
3

Week 0
Primary Endpoint
48 96 144
TxNaïve Adults
HIV-1 RNA
≥1000 c/mL eGFR
≥50 mL/min
1:1 n=866
E/C/F/TAF QD n=867
E/C/F/TDF QD (Stribild, STB)
 Two Phase 3 randomized, double-blind, double-dummy, active-controlled studies
– Study 104 (North America, EU, Asia), Study 111 (North America, EU, Latin America)
– Stratified by HIV-1 RNA, CD4 cell count, geographic region
 Primary endpoint: proportion of patients with HIV-1 RNA <50 copies/mL (Taqman 2.0)
– Non-inferiority (12% margin) based on Week 48 FDA snapshot analysis
– Combined efficacy analysis pre-specified
– Pre-specified Week 48 safety endpoints: serum creatinine, proteinuria, hip BMD, spine BMD
4

Studies 104 and 111: Week 48 Combined Analysis
Median age, years
Sex, %
Male
Female
Race/ethnicity, %
Black or African descent
Hispanic/Latino ethnicity
Median HIV-1 RNA, log
10 c/mL
% with HIV-1 RNA >100,000 c/mL
Median CD4 count, cells/
μL
% with CD4 count <200
Median estimated GFR*, mL/min
*Cockcroft-Gault.
E/C/F/TAF n=866
33
E/C/F/TDF n=867
35
85
15
26
19
4.58
23
404
13
117
85
15
25
19
4.58
23
406
14
114
5

Studies 104 and 111: Week 48 Combined Analysis
Screened
(N=2,175)
Randomized, treated with E/C/F/TAF n=866
5% Discontinued (n=45)
• Adverse event (8)
• Death (1)
• Lack of efficacy (2)
• Withdrew consent (12)
• Lost to follow-up (15)
• Subject non-compliance (2)
• Protocol violation (5)
95% on Treatment n=821
Randomized, treated with E/C/F/TDF n=867
8% Discontinued (n=71)
• Adverse event (13)
• Death (2)
• Lack of efficacy (3)
• Withdrew consent (16)
• Lost to follow-up (18)
• Subject non-compliance (1)
• Protocol violation (6)
• Investigator discretion (7)
• Pregnancy (5)
92% on Treatment n=796
6

Studies 104 and 111: Week 48 Combined Analysis
92
90
Virologic Outcome
E/C/F/TAF (n=866)
E/C/F/TDF (n=867) 100
80
60
40
20
0
Success
4 4
Failure
4
6
No Data
Treatment Difference (95% CI)
Favors E/C/F/TDF Favors E/C/F/TAF
‒12%
‒0.7%
2.0%
4.7%
0 +12%
 E/C/F/TAF was non-inferior to E/C/F/TDF at Week 48 in each study
– 93% E/C/F/TAF vs 92% E/C/F/TDF (Study 104)
– 92% E/C/F/TAF vs 89% E/C/F/TDF (Study 111)
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Studies 104 and 111: Week 48 Combined Analysis
100
80
60
40
20
0
Overall
92
90
800
866
784
867
E/C/F/TAF (n=866)
94
Viral Load
91
87
89
E/C/F/TDF (n=867)
86
Cell Count
93
89
91
629
670
610
672
≤100,000
171
196
174
195
>100,000
HIV-1 RNA (c/mL)
96
112
<200
104
117
703
753
≥200
680
750
CD4 (cells/ μL)
8

Studies 104 and 111: Week 48 Combined Analysis
100
Overall
92
90
80
60
40
20
0
800
866
784
867
E/C/F/TAF (n=866)
92
90
Age
94
91
E/C/F/TDF (n=867)
92 91
Sex
95
87
94 93
Race
88
83
716
777
680
753
84
89
104
114
<50 years ≥50 years
674
733
673
740
Male
126
133
111
127
Female
603
643
607
654
197
223
177
213
Non-Black Black
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Studies 104 and 111: Week 48 Combined Analysis
E/C/F/TAF E/C/F/TDF
300
200
211
181 p=0.024
100
0
0 2 4 8 12 16 20 24 28 32 36 40 44 48 52
Weeks
10

Studies 104 and 111: Week 48 Combined Analysis
E/C/F/TAF n=866
16 (1.8)
7 (0.8)
3
4
7
5
1
6
1
2
0
1
E/C/F/TDF n=867
19 (2.2) Patients analyzed for resistance*, n (%)
Primary Genotypic
Resistance
NRTI Resistance, n
INSTI Resistance, n
Any, n (%)
Study 104, n
Study 111, n
Any
M184V/I
M184V/I + K65R
Any
T66A
E92Q
Q148R
Q148R + T66I/A
Q148R + E92Q 0 1
N155H 1 0
*With 2 consecutive HIV1 RNA ≥50 c/mL after first achieving <50 c/mL and the second ≥400 c/mL; or had ≥400 c/mL at Week 48 or last study visit.
5 (0.6)
3
2
5
3
0
3
2
1
1
0
11

Studies 104 and 111: Week 48 Combined Analysis
Any AE
E/C/F/TAF n=866
%
90
Any drug-related AE
Any Grade 3 or 4 AE
Any drug-related Grade 3 or 4 AE
Any serious AE
Any drug-related serious AE
Any AE-related discontinuation
0.3
0.9
Deaths
* Stroke (1), alcohol intoxication (1).
† Alcohol and drug intoxication (1), myocardial infarction (2).
0.2*
1
8
40
8
E/C/F/TDF n=867
%
90
1
7
42
9
0.2
1.5
0.3
†
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Studies 104 and 111: Week 48 Combined Analysis
E/C/F/TAF n=866
0.9% (8) % (n)
Type • Blood triglycerides increased
• Cerebral infarction, hemorrhagic transformation stroke
• Dyspnea, hyperkeratosis, abdominal distention & pain, back pain, lipodystrophy acquired
• Dysphagia, pharyngitis
• Erectile dysfunction
• Eye irritation, eye pain, eye pruritus
• Proctalgia, penile pain
• Rash erythematous
E/C/F/TDF n=867
1.5% (13)
• Arthropod bite, dermatitis
• Abdominal pain, temporomandibular joint syndrome, headache, depression
• Cardiac arrest
• Dysphagia, nausea, vomiting
• Decreased GFR
• Hyperamylasemia
• Immune reconstitution inflammatory syndrome
• Iridocyclitis
• Nephropathy
• Rash generalized
• Renal failure (2)
• Vomiting, bladder spasm, pyrexia, headache, myalgia, rash maculopapular
13
13

Studies 104 and 111: Week 48 Combined Analysis
AEs in ≥5% of patients, %
Diarrhea
Nausea
Headache
Upper respiratory tract infection
Nasopharyngitis
Fatigue
Cough
Vomiting
Arthralgia
Back pain
Insomnia
Rash
Pyrexia
Dizziness
E/C/F/TAF n=866
17
15
14
11
7
7
7
9
8
8
5
5
7
6
E/C/F/TDF n=867
19
17
13
13
6
5
7
9
8
7
5
4
6
5
14

Studies 104 and 111: Week 48 Combined Analysis
Any grade 3 or 4 lab abnormalities*
Creatine kinase elevation
LDL elevation (fasting)
Hypercholesterolemia (fasting)
Hematuria (quantitative)
AST elevation
Serum amylase elevation
Neutropenia (<1000 cells/µL)
ALT elevation
*≥1% on E/C/F/TAF arm.
E/C/F/TAF n=866
%
20
7
5
2
2
2
2
2
1
E/C/F/TDF n=867
%
20
6
2
1
2
2
3
2
1
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Studies 104 and 111: Week 48 Combined Analysis
 92% of patients treated with E/C/F/TAF achieved virologic suppression through Week 48 (combined analysis)
– Virologic response for E/C/F/TAF, 93% (Study 104) and 92% (Study 111)
– E/C/F/TAF was non-inferior to E/C/F/TDF
– High and similar response rates, irrespective of age, sex, race, HIV-1 RNA, and CD4 cell count
 Low rates of virologic failure, with resistance <1% in both arms
 Both drugs were well tolerated and safe
─ Discontinuations due to AEs were low in both arms
─ 0.9% (8) for E/C/F/TAF vs 1.5% (13) for E/C/F/TDF
─ No proximal tubulopathy cases
─ Common AEs similar between treatment arms
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 Detailed resistance analysis (Margot, Poster #6)
– HIV Drug Resistance Workshop (Feb 21-22)
 Off-target side effects of tenofovir (renal, bone, lipid) (Sax, #143LB)
– Feb 26 th Oral Abstract Session: Cardiovascular, Bone, and Kidney Health
 Patients with mild to moderate renal impairment (eGFR 30-69 mL/min) who switch to E/C/F/TAF, bone mineral density and markers of kidney function improved through 48 weeks (Pozniak, Poster #795)
 Complete results of Studies 104 and 111 submitted for peer-reviewed publication
 Health authority filings submitted and under review in multiple countries
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We extend our thanks to the patients, their partners and families, and all participating Study 104 & 111 investigators
C Achenbach, F Ajana, B Akil, H Albrecht, J Andrade Villanueva, J Angel, A Antela Lopez, J Arribas Lopez, A
Avihingsanon, D Baker, J-G Baril, D Bell, N Bellos, P Benson, J Berenguer, I Bica, A Blaxhult, M Bloch, P
Brachman, I Brar, K Brinkman, C Brinson, B Brown, J Brunetta, J Burack, T Campbell, M Cavassini, A Cheret, P
Chetchotisakd, A Clarke, B Clotet, N Clumeck, C Cohen, P Cook, L Cotte, D Coulston, M Crespo, C Creticos, G
Crofoot, F Cruickshank, J Cunha, E Daar, E DeJesus, J De Wet, M Doroana, R Dretler, M Dube, J Durant, H
Edelstein, R Elion, J Fehr, R Finlayson, D Fish, J Flamm, S Follansbee, H Furrer, F Garcia, J Gatell Artigas, J
Gathe, S Gilroy, P-M Girard, J-C Goffard, E Gordon, P Grant, R Grossberg, C Hare, T Hawkins, R Hengel, K
Henry, A Hite, G Huhn, M Johnson, M Johnson, K Kasper, C Katlama, S Kiertiburanakul, JM Kilby, C Kinder, D
Klein, H Knobel, E Koenig, M Kozal, R Landovitz, J Larioza, A Lazzarin, R LeBlanc, B LeBouche, S Lewis, S
Little, C Lucasti, C Martorell, C Mayer, C McDonald, J McGowan, M McKellar, G McLeod, A Mills, J-M Molina, G
Moyle, M Mullen, C Mussini, R Nahass, C Newman, S Oka, H Olivet, C Orkin, P Ortolani, O Osiyemi, F Palella,
P Palmieri, D Parks, A Petroll, G Pialoux, G Pierone, D Podzamczer Palter, C Polk, R Pollard, F Post, A Pozniak,
D Prelutsky, A Rachlis, M Ramgopal, B Rashbaum, W Ratanasuwan, R Redfield, G Reyes Teran, J Reynes, G
Richmond, A Rieger, B Rijnders, W Robbins, A Roberts, J Ross, P Ruane, R Rubio Garcia, M Saag, J Santana-
Bagur, L Santiago, R Sarmento e Castro, P Sax, B Schmied, T Schmidt, S Schrader, A Scribner, S Segal-
Maurer, B Sha, P Shalit, D Shamblaw, C Shikuma, K Siripassorn, J Slim, L Sloan, D Smith, K Squires, D Stein, J
Stephens, K Supparatpinyo, K Tashima, S Taylor, P Tebas, E Teofilo, A Thalme, M Thompson, W Towner, T
Treadwell, B Trottier, T Vanig, N Vetter, P Viale, G Voskuhl, B Wade, S Walmsley, D Ward, L Waters, D Wheeler,
A Wilkin, T Wilkin, E Wilkins, T Wills, D Wohl, M Wohlfeiler, K Workowski, B Yangco, Y Yazdanpanah, G-P Yeni,
M Yin, B Young, A Zolopa, C Zurawski
This study was funded by Gilead Sciences, Inc.
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