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,1 Jaime Andrade-Villanueva,2 Giovanni DiPerri,3 Jan Van Lunzen,4 Ellen
Koenig,5 Richard Elion,6 Matthias Cavassini,7 Jose Valdez-Madruga,8 Jason Brunetta,9
David Shamblaw,10 Edwin DeJesus,11 Andrew Plummer,12 YaPei Liu,12 and 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; 4Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany;
5Instituto Dominicano de Estudios Virológicos, Santo Domingo, Dominican Republic; 6Whitman-Walker
Health, Washington, DC, USA; 7Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland;
8Centro de Referência 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
E/C/F/TDF
(n=459)
Virologically
Suppressed
Adults
Week 0
n=959
48
96
Switch to E/C/F/TAF
EFV/FTC/TDF
(n=376)
Boosted* ATV + FTC/TDF
(n=601)
n=477
Continue TDF-Based
Regimen
 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
TDF-Based Regimen
n=477
Median age, years
41
40
Female, %
11
11
White
68
66
Black or African descent
18
21
Hispanic/Latino ethnicity
26
17
Median CD4 count, cells/mm3
675
662
0.5
0.8
106
108
Grade 1
8.5
9.2
Grade 2
0.4
0.6
Race, %
Patients with <200 cells/mm3, %
Median estimated GFR, mL/min*
Dipstick proteinuria, %
*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
HIV-1 RNA <50 c/mL, %
100
93
TDF-Based Regimen
n=477
TDF Based
E/C/F/TAF
80
60
4.1
40
1.6
20
1
1
2
6.7
6
0
Success
n=
932
444
Failure
10
6
No Virologic
Data
17
‒12%
0
+12%
27
5
GS-US-292-0109
Virologic Outcome, Prior Treatment Regimens
Primary Endpoint
E/C/F/TAF
TDF-Based Regimen
Patients With HIV-1 RNA <50 c/mL, %
p <0.001
100
97
93
80
60
40
20
0
932
959
444
477
All Prior Regimens
95% CI =
1.6—6.7
241
251
112
125
390
402
183
199
301
306
149
153
Prior
EFV/FTC/TDF
Prior
Boosted
ATV + FTC/TDF
Prior
E/C/F/TDF
—
0.5‒12.1
0.4‒8.7
6
GS-US-292-0109
Virologic Outcome, Prior Treatment Regimens
Primary Endpoint
Patients With HIV-1 RNA <50 c/mL, %
p <0.001
100
97
93
E/C/F/TAF
TDF-Based Regimen
p=0.02
96
90
80
60
40
20
0
95% CI =
932
959
444
477
241
251
112
125
All Prior Regimens
Prior
EFV/FTC/TDF
1.6—6.7
0.5—12.3
390
402
183
199
301
306
149
153
Prior
Boosted
ATV + FTC/TDF
Prior
E/C/F/TDF
0.5‒12.1
0.4‒8.7
7
GS-US-292-0109
Virologic Outcome, Prior Treatment Regimens
Primary Endpoint
Patients With HIV-1 RNA <50 c/mL, %
p <0.001
100
97
93
E/C/F/TAF
p=0.02
TDF-Based Regimen
p=0.02
97
96
90
92
80
60
40
20
0
95% CI =
932
959
444
477
241
251
112
125
390
402
183
199
All Prior Regimens
Prior
EFV/FTC/TDF
Prior
Boosted
ATV + FTC/TDF
1.6—6.7
0.5—12.3
0.9—9.2
301
306
149
153
Prior
E/C/F/TDF
0.4‒8.7
8
GS-US-292-0109
Virologic Outcome, Prior Treatment Regimens
Primary Endpoint
Patients With HIV-1 RNA <50 c/mL, %
p <0.001
100
97
93
E/C/F/TAF
p=0.02
TDF-Based Regimen
p=0.02
97
96
90
p=NS
98
97
301
306
149
153
92
80
60
40
20
0
95% CI =
932
959
444
477
241
251
112
125
390
402
183
199
All Prior Regimens
Prior
EFV/FTC/TDF
Prior
Boosted
ATV + FTC/TDF
Prior
E/C/F/TDF
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*
Age, y
Sex
Race
Adherence
<50*
≥50
Male*
Female
Black
Non-Black*
<95%
≥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
Any abnormality
25
31
Creatine kinase
AST
ALT
Neutropenia
Phosphate (↓)
Uric acid (↑)
Alkaline phosphatase
Leukopenia
Platelets
Total bilirubin
Hemoglobin
Creatinine
10
5
5
4
New Data TK
2
2
<1
<1
<1
<1
0
0
10
7
5
3
3
1
<1
<1
<1
24
<1
<1
Patients, %
11
GS-US-292-0109
Fasting Lipid Results
E/C/F/TAF
Baseline
Week 48
5
Median Values (mg/dL)
250
200
TDF-Based Regimen
Baseline
Week 48
204
4
185
182
181
150
116
100
116
116
120
3.7
3.6
3.6
3
130
125
3.8
114
113
2
52
50
50
1
49
49
0
0
Total Cholesterol
LDL
HDL
Triglycerides
TC:HDL Ratio
p <0.001
p <0.001
p <0.001
p <0.001
p=0.004
 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
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
Participants, %
13
GS-US-292-0109
AEs Leading to Discontinuation
Participants
%
E/C/F/TAF
n=959
TDF-Based Regimen
n=477
0.9
2.5
• Acute renal failure†
• Interstitial nephritisǂ
•
•
•
•
•
Chronic kidney disease
Elevated serum creatinine
Fanconi syndrome, mild jaundice
Increased creatinine
Nephretic colic (nephrolithiasis)
• 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
Renal Events
All Other
Events
†After
cancer chemotherapy, participant hospitalized with neutropenia, sepsis, and multi-system organ failure
hematuria on treatment, subsequent off-treatment diagnosis of Hodgkin’s Lymphoma
ǂRecurrent
14
GS-US-292-0109
DXA Scan Results: Spine BMD
Median % Change in BMD (Q1, Q3)
Change From Baseline to Week 48
All Participants (N=1,369)
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
Median % Change in BMD (Q1, Q3)
Change From Baseline to Week 48
All Participants (N=1,354)
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
100
Patients, %
80
5.8
4.8
36
32
59
64
7.2
7.6
35
37
57
56
60
40
20
0
E/C/F/TAF Week
E/C/F/TAF
TDF
TDF
Baseline
48
Baseline
Week
48
Baseline Week 48 Regimen Regimen
E/C/F/TAF
TDF-Based
Baseline Regimen
Week 48
n=912
n=457
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
100
Patients, %
80
5.8
4.8
36
32
59
64
7.2
7.6
35
37
57
56
60
40
20
0
E/C/F/TAF Week
E/C/F/TAF
TDF
TDF
Baseline
48
Baseline
Week
48
Baseline Week 48 Regimen Regimen
E/C/F/TAF
TDF-Based
Baseline Regimen
Week 48
n=912
n=457
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
100
Patients, %
80
5.8
4.8
36
32
Hip
7.2
35
7.6
37
100
80
60
60
40
40
59
64
57
56
20
20
0
0
E/C/F/TAF Week
E/C/F/TAF
TDF
TDF
Baseline
48
Baseline
Week
48
Baseline Week 48 Regimen Regimen
E/C/F/TAF
TDF-Based
Baseline Regimen
Week 48
n=912
n=457
0.7
0.7
31
26
69
73
1.3
2.1
32
32
67
66
E/C/F/TAF
TDF
TDF 48
Baseline E/C/F/TAF
Week 48
Baseline
Week
Baseline Week 48 Regimen Regimen
E/C/F/TAF
TDF-Based Week
Regimen
Baseline
48
n=902
n=452
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
β-2-m:Cr
30
TDF-Based
Regimen
20
Median % Change
19
18
10
10
9
0
-10
-20
E/C/F/TAF
-21
-18
-33
-30
-40
-50
Each difference between treatment arms
was statistically significant (p <0.001).
-52
-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; β-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 Arastéh, J Arribas López, 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 Fätkenheuer, 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 Jäger, 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 SaavedraSanquirico, L Salazar, L Santiago, T Schmidt, B Schmied, S Schneider, A Scribner, S Segal-Maurer, M
Sension, R Serrão, 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 Fernández, 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