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Joel E. Gallant, MD, MPH Medical Director, Specialty Services Southwest CARE Center Santa Fe, New Mexico State-of-the-ART in Antiretroviral Management.

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Presentation on theme: "Joel E. Gallant, MD, MPH Medical Director, Specialty Services Southwest CARE Center Santa Fe, New Mexico State-of-the-ART in Antiretroviral Management."— Presentation transcript:

1 Joel E. Gallant, MD, MPH Medical Director, Specialty Services Southwest CARE Center Santa Fe, New Mexico State-of-the-ART in Antiretroviral Management FORMATTED: MM/DD/YY New Orleans, Louisiana: December 15-17, 2015

2 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 Cumulative Percent With Event 06121824303642485460 Month Deferred ART Immediate ART Lundgren J, et al. N Engl J Med. 2015 Slide 6 of 38

3 GS104/111: Smaller decline in hip and spine BMD with TAF  Smaller decline in hip and spine BMD with TAF 02448 0 24 48 0 -6 -4 -2 0 2 Wk 0 -6 -4 -2 0 2 =845 =850 797 816 784 773 836 848 789 815 780 767 -1.30 -2.86 -0.66 -2.95 P <.001 Mean % Change From BL Sax P, et al. CROI 2015. Abstract 143. n TAF/FTC/EVG/COBI (n = 866) TDF/FTC/EVG/COBI (n = 867) Slide 17 of 38

4 GS 104/111: TAF vs. TDF: Quantitative Proteinuria Median % Change from Baseline (Q1, Q3) Protein (UPCR) Albumin (UACR) RBP Beta2- microglobulin p <0.001 for all Urine [protein]:Creatinine Ratio 76133168 E/C/F/TAF E/C/F/TDF Baseline 44 mg/g 44 mg/g 5 mg/g 5 mg/g 64 μg/g 67 μg/g 101 μg/g 103 μg/g Sax P, et al. 22nd CROI; Seattle, WA; February 23-26, 2015. Abst. 143LB. Protein (UPCR) Albumin (UACR) RBP Slide 19 of 38

5 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) 4 3 2 1 0 -2 -3 Median % Change in BMD (Q1, Q3) BaselineWeek 24 EVG/COBI/FTC/TAF TDF-Based Regimen Week 48 1.79 -0.28 P <.001 Slide 23 of 38

6 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 Median Change from Baseline 10 0 -10 -0.6 +0.2 -1.8-1.8* -1.5 -2.7* Baseline:565853545650 eGFR CG mL/min eGFR CKD-EPI Cr mL/min/1.73m 2 *P < 0.05. TotalTDFNon-TDF *P < 0.05. 4 2 0 -2 Mean % Change Spine BMD 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

7 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 + DRV Baseline ART 100 80 60 40 20 0 Patients (%) 97 91 2 0 1 9 Week 48 VL < 50 Virologic Failure No Data 94 76 2 11 3 13 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

8 5 2 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 Populations 100 80 60 40 20 0 Virologic Success Virologic Nonresponse No Virologic Data HIV-1 RNA < 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 14 10 6 1 1 < 1 12-12-8-4048 12-12-8-4048 -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

9 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) ScreenBLDay 2Day 4Day 7Day 10Wk 2Wk 3Wk 4Wk 6Wk 8Wk 12Wk 24 1 558410,909370138310171< 50 2 888710,2335671318< 50 3 67,335151,56937,604156511782669753< 50 4 99,291148,37011,797330343217917855< 50 5 34,36220,54446801292570168107< 50 6 16,02414,49937541634162< 50 7 37,60418,597294881961< 50 8 25,07124,36862641377Not done268105< 50 9 14,70710,832Not done516202< 50 10 10,67979785671318< 50 11 50,089273,676160,97468,12938802247784290288147< 50 12 13,50864,10334963296135351 8467< 50 13 28,09333,82937,35026,34353926861< 50 14 15,34815,151399479119898< 506164< 50 15 23,18523,50015,830421719269< 50 Not done< 50 16 11,377391037097143< 50 17 39,10025,82811,879197046014752< 50 18 60,77173,06931,1702174692358156< 50 19 82,803106,32035,517290289735216876< 50 20 51907368343314756< 50 Slide 32 of 38

10 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/mL by Snapshot Algorithm (%) 100 80 60 40 20 0 BL412242836487296 Induction PhaseMaintenance 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

11 Recent Switch Studies: Suppressed Patients TrialFromToOutcome GS-123 TDF/FTC + RALEVG/COBI/FTC/TDF ✔ GS-264 TDF/FTC/EFVRPV/FTC/TDF ✔ Strategy-NNRTI TDF/FTC + NNRTIEVG/COBI/FTC/TDF ✔ Strategy-PI TDF/FTC + PI/rEVG/COBI/FTC/TDF ✔ SPIRIT 2 NRTI + PI/rRPV/FTC/TDF ✔ SPIRAL 2 NRTI + PI/r (exp’d pts)2 NRTI + RAL ✔ SALT ATV/r + 2 NRTIATV/r + 3TC ✔ OLE LPV/r + 2 NRTIsLPV/r + 3TC ✔ GS-109 TDF-based ARTEVG/COBI/FTC/TAF ✔ STRIIVING Suppressive ARTDTG/ABC/3TC ✔ ATLAS-M ATV/r + 2 NRTIsATV/r + 3TC ✔ GS-119 “Salvage regimen” (exp’d pts)EVG/COBI/FTC/TAF + DRV ✔ LATTE CAB or EFV + 2 NRTIsCAB + RPV ✔ SWITHCMRK 2 NRTI + LPV/r (exp’d pts)2 NRTI + RAL ✗ MARCH 2 NRTI + PI/rPI/r + MVC ✗ HARNESS 2 NRTI + 3 rd AgentATV/r + RAL ✗ Adapted from David Wohl Slide 34 of 38


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