The Managerial Task of Installing Wellconceived Stateoftheart Information and

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State-of-the-Fine art in Antiretroviral Management Joel East. Gallant, MD, MPH Medical Managing director, Specialty Services Southwest Intendance Heart Santa Fe, New Mexico FORMATTED: MM/DD/YY New Orleans, Louisiana: December xv -17, 2015

Slide 6 of 38 START: 57% Reduced Risk of Serious Events or Death With Immediate ART one. viii% vs iv. ane% in deferred vs immediate arms experienced serious AIDS or non-AIDS related event or death: Hour = 0. 43 (95% CI: 0. thirty to 0. 62); P <. 001 Cumulative Per centum With Event § 10 eight Deferred Art vi iv Immediate Art 2 0 0 6 Lundgren J, et al. N Engl J Med. 2015 12 18 24 30 36 Month 42 48 54 threescore

Slide 17 of 38 GS 104/111: Smaller decline in hip and spine BMD with TAF § Smaller decline in hip and spine BMD with TAF Mean % Modify From BL TAF/FTC/EVG/COBI (due north = 866) TDF/FTC/EVG/COBI (n = 867) 2 0 -2 -4 -6 0 P <. 001 -1. xxx -ii. 86 0 n =845 n =850 24 Wk 797 816 Sax P, et al. CROI 2015. Abstract 143. 48 784 773 2 0 -2 -iv -six 0 P <. 001 -0. 66 -2. 95 0 836 848 24 Wk 789 815 48 780 767

Slide nineteen of 38 GS 104/111: TAF vs. TDF: Quantitative Proteinuria Urine [protein]: Creatinine Ratio Median % Change from Baseline (Q one, Q 3) Protein (UPCR) Albumin (UACR) RBP 76 Beta ii microglobulin 133 168 75 51 50 24 20 25 7 nine 0 -25 -three p <0. 001 for all -v -32 -50 Baseline 44 mg/yard Eastward/C/F/TAF E/C/F/TDF 5 mg/g Sax P, et al. 22 nd CROI; Seattle, WA; February 23 -26, 2015. Abst. 143 LB. 64 μg/g 67 μg/k 101 μg/one thousand 103 μg/g

Slide 23 of 38 GS-109: Switch from TDF-based Regimens to Due east/C/F/TAF: Renal and Os Outcomes • Hip BMD was similarly increased for pts treated with TAF regimen Median % Change in BMD (Q 1, Q iii) 4 3 two i 0 -1 -2 -iii Baseline EVG/COBI/FTC/TAF TDF-Based Regimen EVG/COBI/ FTC/TAF (n = 959) i. 79 P <. 001 -0. 28 Week 24 Week 48 Mills A, et al. IAS 2015. Abstract TUAB 0102. Renal Events Leading to Discontinuation Regimen TDF-Based Regimen (n = 477) § Astute renal failure § Interstitial nephritis § Chronic kidney illness § Elevated serum creatinine § Fanconi syndrome (mild jaundice) § Increased creatinine § Nephretic colic (nephrolithiasis)

GS-112: Switching to E/C/F/TAF Regimen With Renal Impairment (e. GFR xxx -threescore) Slide 24 of 38 Multicenter, open-label phase Iii trial, N=242 (158 on TDF, 84 on non-TDF-based regimen) Changes in e. GFR to Wk 48 Total TDF Total Non-TDF 4 0 -ten Baseline: *P < 0. 05. +0. 2 -0. 6 -1. 8*-1. five -2. 7* 56 58 53 54 56 50 e. GFRCG yard. Fifty/min due east. GFRCKD-EPI Cr m. L/min/ane. 73 m 2 Gupta Southward, et al. IAS 2015. Abstruse TUAB 0103. Hateful % Change Spine BMD Median Modify from Baseline ten Changes in spinal BMD to Wk 48 2 two. 95* 2. 29* 0. 99 0 -2 *P < 0. 05.

Slide 26 of 38 GS 119: Virologic Suppression Afterwards Switch to EVG/COBI/FTC/TAF + DRV Like rates of maintained virologic suppression at Wk 24, but significantly college rates with switch vs baseline Art at Wk 48 Patients (%) 100 97 91 80 Treatment deviation: 5. three% (95% CI: -three. 4 to 17. four; P =. 23) 60 EVG/COBI/FTC/TAF + DRV Baseline ART 94 76 Treatment difference: 18. iii% (95% CI: iii. 5 to 33; P =. 004) forty 20 0 2 0 VL< 50 Virologic Failure Week 24 Huhn S, et al. ID Week 2015. Abstruse 726. i nine No Data 2 VL < 50 11 Virologic Failure Week 48 thirteen 3 No Data

Slide 29 of 38 STRIIVING: Virologic Outcomes at Wk 24 § Switch to DTG/ABC/3 TC noninferior to maintaining baseline ART § No cases of protocol-defined virologic failure – 3 pts in DTG/ABC/three TC arm (i%) and 4 pts in BL Art arm (1%) had VL > l but < 100 through Wk 24 Main Efficacy Assay: ITT-Exposed and Per Protocol Populations HIV-one RNA < 50 c/1000. L (%) 100 85 88 93 93 DTG/ABC/3 TC (ITT-E, n = 274) Baseline ART (ITT-E, due north = 277) DTG/ABC/3 TC (PP, due north = 220) Baseline ART (PP, due north = 215) 80 sixty forty 20 0 one 1<12 Virologic Success 14 10 -3. 4 -9. 1 -12 -8 2. 3 -4 0 4 PP Population 6 5 Virologic Nonresponse Data Trottier B, et al. ICAAC 2015. Baseline Art DTG/ABC/three TC ITT-E Population viii 12 -0. 3 -iv. 9 -12 -8 -iv 4. 4 0 iv

Slide 32 of 38 PADDLE: All Pts Virologically Suppressed past Wk 8 of DTG + 3 TC § Included 4 pts with VL > 100, 000 at BL Pt # 1 two three 4 v 6 7 8 9 ten 11 12 xiii 14 15 16 17 eighteen 19 20 Screen BL Day 2 Day 4 Twenty-four hours 7 5584 8887 67, 335 99, 291 34, 362 16, 024 37, 604 25, 071 14, 707 10, 679 50, 089 13, 508 28, 093 15, 348 23, 185 11, 377 39, 100 lx, 771 82, 803 5190 10, 909 10, 233 151, 569 148, 370 20, 544 14, 499 18, 597 24, 368 10, 832 7978 273, 676 64, 103 33, 829 xv, 151 23, 500 3910 25, 828 73, 069 106, 320 7368 3701 5671 37, 604 11, 797 4680 3754 2948 6264 Not done 5671 160, 974 3496 37, 350 3994 15, 830 370 11, 879 31, 170 35, 517 3433 383 318 1565 3303 1292 1634 819 1377 516 318 68, 129 3296 26, 343 791 4217 97 1970 2174 2902 147 101 < 50 1178 432 570 162 61 Not done 202 < 50 3880 135 539 198 192 143 460 692 897 56 Figueroa MI, et al. EACS 2015. Abstruse 1066. HIV-ane RNA (copies/m. L) Twenty-four hours 10 Wk two Wk iii 71 < 50 266 179 168 < 50 2247 351 268 98 69 < 50 147 358 352 < 50 97 178 107 < 50 105 < fifty 784 351 61 < fifty 52 156 168 < 50 53 55 < 50 < l 290 84 < 50 61 < fifty 76 < 50 Wk 4 Wk 6 Wk 8 Wk 12 Wk 24 < l < l < 50 288 67 < 50 64 < l < 50 < 50 < 50 147 < l Not done < 50 < l < 50 < 50 < 50 < 50 < 50 < fifty < fifty < fifty < 50 < l < 50 < 50 < 50 < fifty < 50

Slide 33 of 38 LATTE: Virologic Success Through Maintenance Calendar week 96 VL < 50 c/k. L past Snapshot Algorithm (%) 100 § Induction Phase Maintenance Phase 84% 75% 68% 63% eighty sixty 40 CAB 10 mg (north = 60) CAB thirty mg (n = 60)* CAB threescore mg (due north = 61) EFV 600 mg (n = 62) 20 0 BL 4 12 24 28 48 72 Wks vi pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48 Margolis D, et al. CROI 2015. Abstract 554 LB. 36 96 *Cabotegravir 30 mg selected for future development

Slide 34 of 38 Recent Switch Studies: Suppressed Patients Trial From To Consequence 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 ✔ Table salt ATV/r + 2 NRTI ATV/r + three TC ✔ OLE LPV/r + 2 NRTIs LPV/r + 3 TC ✔ GS-109 TDF-based Fine art EVG/COBI/FTC/TAF ✔ STRIIVING Suppressive ART DTG/ABC/iii TC ✔ ATLAS-K ATV/r + 2 NRTIs ATV/r + 3 TC ✔ 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 + MVC ✗ HARNESS ii NRTI + 3 rd Agent ATV/r + RAL ✗ Adapted from David Wohl

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