Joel E. Gallant, MD, MPHMedical Director, Specialty Services

Southwest CARE CenterSanta Fe, New Mexico

State-of-the-ART in Antiretroviral Management

FORMATTED: MM/DD/YY

New Orleans, Louisiana: December 15-17, 2015

START: 57% Reduced Risk of Serious Events or Death With Immediate ART 1.8% vs 4.1% in deferred vs immediate arms experienced serious AIDS or

non-AIDS related event or death: HR = 0.43 (95% CI: 0.30 to 0.62); P < .001

10

8

6

4

2

0

Cum

ulat

ive

Per

cent

With

Eve

nt

0 6 12 18 24 30 36 42 48 54 60Month

Deferred ART

Immediate ART

Lundgren J, et al. N Engl J Med. 2015

Slide 6 of 38

GS104/111: Smaller decline in hip and spine BMD with TAF Smaller decline in hip and spine BMD with TAF

0 24 48 0 24 480

-6-4-202

Wk Wk

0-6-4-202

=845=850

797816

784773

836848

789815

780767

-1.30-2.86

-0.66-2.95

P < .001 P < .001

Mea

n %

C

hang

e Fr

om

BL

Sax P, et al. CROI 2015. Abstract 143.

n n

TAF/FTC/EVG/COBI (n = 866)TDF/FTC/EVG/COBI (n = 867)

Slide 17 of 38

GS 104/111: TAF vs. TDF: Quantitative ProteinuriaM

edia

n %

Cha

nge

from

B

asel

ine

(Q1,

Q3)

Protein (UPCR)

Albumin (UACR) RBP Beta2-

microglobulin

p <0.001for all

Urine [protein]:Creatinine Ratio

-50

-25

0

25

50

75

-3 -5

9

-32

207

51

24

76 133 168E/C/F/TAFE/C/F/TDF

Baseline 44mg/g

44mg/g

5mg/g

5mg/g

64μg/g

67μg/g

101μg/g

103μg/g

Sax P, et al. 22nd CROI; Seattle, WA; February 23-26, 2015. Abst. 143LB.

Protein (UPCR)

Albumin (UACR) RBP

Slide 19 of 38

GS-109: Switch from TDF-based Regimens to E/C/F/TAF: Renal and Bone Outcomes

• Hip BMD was similarly increased for pts treated with TAF regimen

Mills A, et al. IAS 2015. Abstract TUAB0102.

Regimen Renal Events Leading to Discontinuation

EVG/COBI/FTC/TAF (n = 959)

Acute renal failure Interstitial nephritis

TDF-Based Regimen (n = 477) Chronic kidney disease

Elevated serum creatinine

Fanconi syndrome (mild jaundice) Increased creatinine

Nephretic colic (nephrolithiasis)

43210

-1-2-3M

edia

n %

Cha

nge

in B

MD

(Q1,

Q3)

Baseline Week 24

EVG/COBI/FTC/TAFTDF-Based Regimen

Week 48

1.79

-0.28

P < .001

Slide 23 of 38

GS-112: Switching to E/C/F/TAF Regimen With Renal Impairment (eGFR 30-60)

Changes in eGFR to Wk 48 Changes in spinal BMD to Wk 48

Gupta S, et al. IAS 2015. Abstract TUAB0103.

Total TDF Non-TDF

Med

ian

Cha

nge

from

B

asel

ine

10

0

-10

-0.6+0.2

-1.8 -1.8*-1.5-2.7*

Baseline: 56 58 53 54 56 50eGFRCG

mL/mineGFRCKD-EPI Cr

mL/min/1.73m2

*P < 0.05.

Total TDF Non-TDF

*P < 0.05.

4

2

0

-2Mea

n %

Cha

nge

Spi

ne B

MD

2.95*2.29*

0.99

Multicenter, open-label phase III trial, N=242 (158 on TDF, 84 on non-TDF-based regimen)

Slide 24 of 38

GS 119: Virologic Suppression After Switch to EVG/COBI/FTC/TAF + DRV

Similar rates of maintained virologic suppression at Wk 24, but significantly higher rates with switch vs baseline ART at Wk 48

Huhn S, et al. ID Week 2015. Abstract 726.Week 24

VL< 50 Virologic Failure

No Data

EVG/COBI/FTC/TAF + DRVBaseline ART100

80

60

40

20

0

Pat

ient

s (%

)

9791

2 0 19

Week 48

VL < 50 Virologic Failure

No Data

94

76

211

313

Treatment difference: 5.3% (95% CI: -3.4 to 17.4; P = .23)

Treatment difference: 18.3% (95% CI: 3.5 to 33; P = .004)

Slide 26 of 38

52

STRIIVING: Virologic Outcomes at Wk 24

Switch to DTG/ABC/3TC noninferior to maintaining baseline ART No cases of protocol-defined virologic failure

– 3 pts in DTG/ABC/3TC arm (1%) and 4 pts in BL ART arm (1%) had VL > 50 but < 100 through Wk 24

Trottier B, et al. ICAAC 2015.

Primary Efficacy Analysis: ITT-Exposed and Per Protocol Populations100

80

60

40

20

0VirologicSuccess

VirologicNonresponse

No Virologic Data

HIV

-1 R

NA

< 50

c/

mL

(%)

DTG/ABC/3TC (ITT-E, n = 274)Baseline ART (ITT-E, n = 277)DTG/ABC/3TC (PP, n = 220)Baseline ART (PP, n = 215)

85 88 93 93

14 10 61 1 < 1

12-12 -8 -4 0 4 8

12-12 -8 -4 0 4 8

-4.9-0.3

4.4

2.3-9.1

ITT-E Population

PP Population

-3.4

DTG/ABC/3TCBaseline ART

Slide 29 of 38

PADDLE: All Pts Virologically Suppressed by Wk 8 of DTG + 3TC Included 4 pts with VL > 100,000 at BL

Figueroa MI, et al. EACS 2015. Abstract 1066.

Pt #HIV-1 RNA (copies/mL)

Screen BL Day 2 Day 4 Day 7 Day 10 Wk 2 Wk 3 Wk 4 Wk 6 Wk 8 Wk 12 Wk 241 5584 10,909 3701 383 101 71 < 50 < 50 < 50 < 50 < 50 < 50 < 502 8887 10,233 5671 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 503 67,335 151,569 37,604 1565 1178 266 97 53 < 50 < 50 < 50 < 50 < 504 99,291 148,370 11,797 3303 432 179 178 55 < 50 < 50 < 50 < 50 < 505 34,362 20,544 4680 1292 570 168 107 < 50 < 50 < 50 < 50 < 50 < 506 16,024 14,499 3754 1634 162 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 507 37,604 18,597 2948 819 61 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 508 25,071 24,368 6264 1377 Not done 268 105 < 50 < 50 < 50 < 50 < 50 < 509 14,707 10,832 Not done 516 202 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

10 10,679 7978 5671 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 5011 50,089 273,676 160,974 68,129 3880 2247 784 290 288 147 < 50 < 50 < 5012 13,508 64,103 3496 3296 135 351 351 84 67 < 50 < 50 < 50 < 5013 28,093 33,829 37,350 26,343 539 268 61 < 50 < 50 < 50 < 50 < 50 < 5014 15,348 15,151 3994 791 198 98 < 50 61 64 < 50 < 50 < 50 < 5015 23,185 23,500 15,830 4217 192 69 < 50 < 50 < 50 Not done < 50 < 50 < 5016 11,377 3910 370 97 143 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 5017 39,100 25,828 11,879 1970 460 147 52 < 50 < 50 < 50 < 50 < 50 < 5018 60,771 73,069 31,170 2174 692 358 156 < 50 < 50 < 50 < 50 < 50 < 5019 82,803 106,320 35,517 2902 897 352 168 76 < 50 < 50 < 50 < 50 < 5020 5190 7368 3433 147 56 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

Slide 32 of 38

LATTE: Virologic Success Through Maintenance Week 96

6 pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48

Margolis D, et al. CROI 2015. Abstract 554LB.

VL

< 50

c/m

L by

S

naps

hot A

lgor

ithm

(%

)

100

80

60

40

20

0BL 4 12 24 28 36 48 72 96

Induction Phase Maintenance Phase

CAB 10 mg (n = 60)CAB 30 mg (n = 60)*CAB 60 mg (n = 61)EFV 600 mg (n = 62)

68%63%

84%75%

Wks

*Cabotegravir 30 mg selected for future development

Slide 33 of 38

Recent Switch Studies: Suppressed PatientsTrial From To Outcome

GS-123 TDF/FTC + RAL EVG/COBI/FTC/TDF ✔GS-264 TDF/FTC/EFV RPV/FTC/TDF ✔Strategy-NNRTI TDF/FTC + NNRTI EVG/COBI/FTC/TDF ✔Strategy-PI TDF/FTC + PI/r EVG/COBI/FTC/TDF ✔SPIRIT 2 NRTI + PI/r RPV/FTC/TDF ✔SPIRAL 2 NRTI + PI/r (exp’d pts) 2 NRTI + RAL ✔SALT ATV/r + 2 NRTI ATV/r + 3TC ✔OLE LPV/r + 2 NRTIs LPV/r + 3TC ✔GS-109 TDF-based ART EVG/COBI/FTC/TAF ✔STRIIVING Suppressive ART DTG/ABC/3TC ✔ATLAS-M ATV/r + 2 NRTIs ATV/r + 3TC ✔GS-119 “Salvage regimen” (exp’d pts) EVG/COBI/FTC/TAF + DRV ✔LATTE CAB or EFV + 2 NRTIs CAB + RPV ✔SWITHCMRK 2 NRTI + LPV/r (exp’d pts) 2 NRTI + RAL ✗MARCH 2 NRTI + PI/r PI/r + MVC ✗HARNESS 2 NRTI + 3rd Agent ATV/r + RAL ✗

Adapted from David Wohl

Slide 34 of 38