Efficacy and safety of tenofovir alafenamide fumarate in ...
1508 Efficacy and Safety of Tenofovir Alafenamide in HIV ...
Transcript of 1508 Efficacy and Safety of Tenofovir Alafenamide in HIV ...
IntroductionTenofovir alafenamide (TAF) – Nucleos(t)ide reverse-transcriptase inhibitor in most guideline-recommended
regimens– Replaced tenofovir disoproxil fumarate (TDF) (IAS–USA)1
– Included in addition to TDF (BHIVA, US DHHS)2,3
Emtricitabine (FTC)/TAF vs FTC/TDF4
– Similar efficacy (94% vs 93%) with less renal and bone toxicities FTC/TAF-containing single-tablet regimens– Elvitegravir/cobicistat/FTC/TAF and rilpivirine/FTC/TAF– Can be used in patients with estimated glomerular filtration rate (eGFR)
as low as 30 mL/min5,6
Black adults are disproportionately affected by HIV and kidney disease7,8
Methods
Results
Efficacy and Safety of Tenofovir Alafenamide in HIV-Infected Black Adults: Subgroup Analysis of a Randomized, Double-blind Switch Study
Edwin DeJesus,1 Rick Ellion,2 Moti Ramgopal,3 Barbara Wade,4 Louis Sloan,5 Howard Edelstein,6 Gerald Pierone,7 Jihad Slim,8 Jeffrey Stephens,9 Mingjin Yan,10 Cecilia Tran-Muchowski,10 Martin Rhee101Orlando Immunology Center, Orlando, FL; 2Whitman-Walker Health, Washington, DC; 3Midway Immunology and Research Center, Fort Pierce, FL; 4Infectious Diseases Associates of Northwest Florida PA, Pensacola, FL; 5North Texas Infectious Diseases Consultants, Dallas, TX;
6Alameda Health System–Highland Hospital, Oakland, CA; 7AIDS Research & Treatment Center of the Treasure Coast, Vero Beach, FL; 8Saint Michael's Medical Center, Newark, NJ; 9Mercer University School of Medicine, Macon, GA; 10Gilead Sciences, Inc., Foster City, CA
Presented at IDWeek™ 2016, October 26–30, 2016, New Orleans, LA © 2016 Gilead Sciences, Inc. All rights reserved.
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Gilead Sciences, Inc. 333 Lakeside Drive
Foster City, CA 94404 800-445-3252
References1. Günthard HF, et al. JAMA 2016;316:191-210; 2. AIDSinfo, 2016. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf; 3. British HIV Association, 2016. http://www.bhiva.org/documents/Guidelines/Treatment/2016/treatment-guidelines-2016-interim-update.pdf; 4. Gallant JE, et al. Lancet HIV2016;3:e158-65; 5. Genvoya [SmPC]. Foster City, CA: Gilead Sciences, Inc., 2015; 6. Odefsey [SmPC]. Foster City, CA: Gilead Sciences, Inc., 2016; 7. Centers for Disease Control and Prevention, 2016. http://www.cdc.gov/hiv/group/racialethnic/africanamericans/index.html; 8. Choi AI, et al. Am J Med 2009;122:672-8.
AcknowledgmentsWe extend our thanks to the patients and their families, and all participating study investigators and staff: J. Angel, N. Bellos, P. Benson, C. Brinson, J. Brunetta, A. Cheret, A. Clarke, N. Clumeck, B. Conway, D. Coulston, G. Crofoot, E. Daar, E. DeJesus, C. Dietz, H. Edelstein, R. Elion, J. Flamm, J. Gallant, J. Gathe, R. Grossberg, B. Hare, K. Henry, R. Hsu, M. Johnson, C. Kinder, D. Klein, LaMarca, A. Lazzarin, K. Lichtenstein, C. Lucasti, F. Maggiolo, C. McDonald,J. McGowan, A. Mills, M. Mogyoros, J. Morales-Ramirez, G. Moyle, H. Olivet, C. Orkin, O. Osiyemi, M. Para, A. Petroll, G. Pierone, C. Polk, F. Post, D. Prelutsky, F. Raffi, M. Ramgopal, B. Rashbaum, J. Reynes, G. Richmond, A. Roberts, P. Ruane, M. Saag, J. Santana-Bagur, L. Santiago, P. Sax, A. Scarsella,G. Schembri, S. Segal-Maurer, P. Shalit, D. Shamblaw, L. Slama, J. Slim, L. Sloan, M. Sokol-Anderson, D. Stein, J. Stephens, M. Thompson, T. Vanig, G. Voskuhl, B. Wade, S. Walmsley, D. Ward, M. Wohlfeiler, Y. Yazdanpanah, B. Young, C. Zurawski. This study was funded by Gilead Sciences, Inc.
In HIV-infected black patients, FTC/TAF (vs FTC/TDF)demonstrated:– High rates of virologic suppression– Improved bone and renal safety – Small increases in lipids with no differences in total
cholesterol:HDL ratioEfficacy and safety of FTC/TAF in black patients were similar to those in nonblack patientsFTC/TAF is an important backbone for black patients living with HIV
Conclusions
94
1 4
90
3 7
Patie
nts,
%
FTC/TDF FTC/TAF
Treatment Difference (95% CI)Virologic Outcome
Treatment Difference (95% CI)
0
20
40
60
80
100
Success Failure No Data
FTC/TAF (n=69)FTC/TDF (n=67)
FTC/TDF FTC/TAF
94
06
94
1 5
-3.6 4.6
0.5
-10 -5 0 5 10 15
-5.7 14.9
4.6
-10 -5 0 5 10 15
Patie
nts,
%
Virologic OutcomeFTC/TAF (n=263)FTC/TDF (n=262)
Success Failure No Data0
20
40
60
80
100
Efficacy at Week 48 (Snapshot)Black Patients
Mean change in CD4 cell count: FTC/TAF 20 vs FTC/TDF 33 cells/µL
Mean change in CD4 cell count: FTC/TAF 19 vs FTC/TDF 19 cells/µL
Nonblack Patients
Med
ian
Cha
nge,
mL/
min
Med
ian
% C
hang
e
-50
-25
0
25
50Urine
Albumin:CrUrine
Protein:CrUrine
β2M:CrUrine
RBP:Cr
-20
-10
0
10
20 eGFR
FTC/TAF FTC/TDF
Med
ian
Cha
nge,
mL/
min
Med
ian
% C
hang
e
-50
-25
0
25
50Urine
Albumin:CrUrine
Protein:CrUrine
β2M:CrUrine
RBP:Cr
-20
-10
0
10
20 eGFR
FTC/TAF FTC/TDF
-17.2
0.5
-3.8 -16.6
15.4
14.5 12.7 14.79.1 3.3
p=0.01 p=0.01 p=0.31 p=0.01 p=0.01
8.2 2.8
-13.7-8.8
-20.7-42.9
7.311.0
18.8 22.5
p <0.001 p <0.001 p <0.001 p <0.001 p <0.001
Change in Renal BiomarkersBlack Patients
Cr, creatinine; RBP, retinol-binding protein; β2M, β2-microglobulin.
Nonblack Patients TotalCholesterol
LDL HDL Triglycerides Total Cholesterol:HDL
Med
ian
at W
eek
48, m
g/dL
Med
ian
at W
eek
48, m
g/dL
0
TotalCholesterol
LDL HDL Triglycerides Total Cholesterol:HDL
0
1
2
3
4
5
0
50
100
150
200
250 p=0.01
p <0.05
p=0.04
p=0.70
p=0.70 210
183
133116
6254
108
97
3.4 3.4
1
2
3
4
5
0
50
100
150
200
250 p <0.001
p <0.001
p=0.41
p <0.01
p=0.03
197183
128114
4948
134118
3.9
3.6
FTC/TAF FTC/TDFIncrease from baseline
Decrease from baseline
LipidsBlack Patients
Nonblack Patients
Mea
n %
Cha
nge
inB
MD
(95%
CI)
Mea
n %
Cha
nge
inB
MD
(95%
CI)
1.2
-0.6
-2
0
2
4
BL 24 48
Spine Hip
Spine Hip
0.4
0.2
-2
0
2
4
BL 24 48FTC/TAF 66 64 63
FTC/TDF 64 63 6166 64 6363 61 60
p <0.01 p=0.84
1.6
-0.1
-2
0
2
4
BL 24 48
1.3
-0.2
-2
0
2
4
BL 24 48
p <0.001p <0.001
FTC/TAF 254 245 236FTC/TDF 255 246 244
254 244 236253 243 242
Change in Bone Mineral DensityBlack Patients
Nonblack PatientsFTC/TAF
n=333FTC/TDF
n=330)97–22( 94 )87–22( 84 )egnar( y ,ega naideM
)61( 45 )41( 84 )%( n ,elameF )%( n ,ecaR
)77( 352 )37( 442 etihW )02( 76 )12( 96 *tnecsed nacirfA ro kcalB )3( 01 )6( 02 rehtO )42( 87 )41( 84 )%( n ,yticinhte onitaL/cinapsiH
Median CD4 count, cells/mm3 426 366 <200 cells/mm3 )1( 4 )2( 5 )%( n ,
001 99 nim/Lm ,RFGe naideM0.5 2.5 y ,tnemllorne erofeb FDT/CTF no noitarud naideM
)%( n ,tnega dr3 fo esU)54( 051 )74( 551 IP detsooB )55( 081 )35( 871 tnega dr3 detsoobnU
Baseline Demographics and Disease Characteristics
*Blacks: self-identified as black or of African descent.
kcalbnoNkcalBPatients, n F TC/TAF, n=69 FTC/TDF, n=67 FTC/TAF, n=263 FTC/TDF, n=262
)%1( 2 )%3( 7 )%2( 1 0 llarevO0 1 0 0 deretla doom/ainmosnI0 1 0 0 aigahpsyD0 1 0 0 noitallirbif lairtA0 1 0 0 aehrraiD0 1 0 0 amede larehpireP0 1 0 0 esodrevO0 1 0 0 amohpmyL
Increased serum creatinine 0 1 0 01 0 0 0 sumsenet latceR
Feeling abnormal/headache 0 0 0 1
Adverse Events Leading to Study Drug Discontinuation
kcalbnoNkcalBAdverse Events, %* FTC/TAF, n=69 FTC/TDF, n=67 FTC/TAF, n=263 FTC/TDF, n=262
1 ehcadaeH 3 9 7 31 hguoC 3 3 5 5
5 6 6 9 sitihcnorB3 4 6 9 niap kcaB
Upper respiratory tract infection 7 10 10 156 8 6 7 sitignyrahposaN01 01 9 6 aehrraiD3 6 2 6 aiglarhtrA5 6 2 4 eugitaF8 4 3 1 sitisuniS
Adverse Events
*Reported in >5% in overall FTC/TAF or FTC/TDF group.
kcalbnoNkcalBPatients, %* 262=n ,FDT/CTF 362=n ,FAT/CTF 76=n ,FDT/CTF 96=n ,FAT/CTF
4 5 01 7 niburilib latoT3 6 2 6 LDL2 2 2 4 airusocylG3 4 5 3 esanik enitaerC1 3 0 3 loretselohc latoT1< 1 2 2 aimecylgrepyH
1 1 8 1 esalymA2 1< 5 1 TGG1< 2 3 1 airutameH
1 1 3 1 TSA
Grade 3–4 Lab Abnormalities
*Reported in >1% in overall FTC/TAF or FTC/TDF group.
n=333
n=330
FTC/TAF qd*FTC/TDF Placebo qdContinue 3rd Agent
FTC/TDF qdFTC/TAF Placebo qd*Continue 3rd Agent
Virologically Suppressed (<50 copies/mL)■ FTC/TDF + 3rd Agent■ eGFR ≥50 mL/min
9648Week 0Primary Endpoint
HIV-1 RNA <50 Copies/mLSecondaryEndpoint
Switch From FTC/TDF to FTC/TAFRandomized, double-blind, double-dummy, active-controlled study(NCT02121795)
*FTC/TAF Dose: – 200/10 mg with boosted PIs– 200/25 mg with unboosted 3rd agents (ie, non-PIs)
Passcode: 1508