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.

1508

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