Switch to E/C/F/TAF + DRV Study GS-US-292-0119
A study (GS-US-292-0119) on switching to E/C/F/TAF + DRV regimen for HIV treatment in patients with prior failures and resistance. The study design, baseline characteristics, and pharmacokinetic results are presented, demonstrating non-inferiority of E/C/F/TAF compared to standard regimen. Explore the impact on treatment success and key findings from this research.
Uploaded on | 0 Views
Download Presentation
Please find below an Image/Link to download the presentation.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author. If you encounter any issues during the download, it is possible that the publisher has removed the file from their server.
You are allowed to download the files provided on this website for personal or commercial use, subject to the condition that they are used lawfully. All files are the property of their respective owners.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author.
E N D
Presentation Transcript
Switch to E/C/F/TAF + DRV Study GS-US-292-0119
GS-US-292-0119 Study: switch to E/C/F/TAF + DRV Design Randomisation* 2: 1 Open-label W48 W144 W24 18 years N = 89 4 months with HIV RNA < 50 c/mL on ART containing DRV/r 2 prior failures + 2 class resistance by historical genotype ( 3 TAMS + K65R) No Q151M, T69ins, or DRV mutations Historical genotype with no INSTI-R INSTI-na ve or suppressed on INSTI eGFR > 50 mL/min E/C/F/TAF + DRV 800 mg QD E/C/F/TAF + DRV 800 mg QD Baseline regimen N = 46 Objective Primary Endpoint: proportion with treatment success (HIV RNA < 50 c/mL) at W24, ITT, FDA snapshot: non-inferiority of E/C/F/TAF with a lower margin of 12%, by 2-sided 95% CI Huhn GD, JAIDS 2017; 74:193.200 GS-US-292-0119
GS-US-292-0119 Study: switch to E/C/F/TAF + DRV Baseline characteristics and disposition at W48 E/C/F/TAF + DRV, N = 89 Baseline regimen, N = 46 Median age, years 49 47 Female, % 18 39 CD4/mm3, median 519 518 eGFR (Cockroft-Gault), mL/min, median 99 100 Baseline regimen Number of pills/day, median 6 pills/day, % At least BID dosing, % TDF / ABC / Other NRTIs, % RAL 5 40 65 5 37 65 61 / 11 / 12 56 54 /11 / 13 50 Resistance 2-class / 3-class resistance, % M184V/I K65R TAMs ( 3 TAMs) NNRTI-R / PI-R GSS at study entry, mean 70 / 26 85 20 43.8 (16.8) 89 / 38 2.45 74 / 20 78 30 39.1 (17.4) 87 / 28 2.56 Discontinuation before W24, N (%) Lack of efficacy / Adverse event 2 (2.2%) 0 / 0 5 (10.9%) 0 / 0 Huhn GD, JAIDS 2017; 74:193.200 GS-US-292-0119
GS-US-292-0119 Study: switch to E/C/F/TAF + DRV Pharmacokinetic substudy Results (N = 15) Once-daily dosing of E/C/F/TAF (150/150/200/10 mg) + DRV 800 mg ASC Cmax (ng/mL) Cthough (ng/mL) Mean (% CV) (ng*h/mL) EVG 26 400 (44) 2 180 (35) 464 (79) DRV 76 500 (43) 6 670 (25) 1 250 (99) TAF 89,9 (45) 98,1 (58) NA COBI 7 900 (43) 997 (30) 36 (129) EVG Ctrough>10-fold above IC95(45 ng/mL) DRV Ctrough>22-fold above EC50(55 ng/mL) TAF exposures in efficacious range demonstrated in pivotal Phase 3 studies COBI exposure associated with robust boosting TFV exposure (mean [%CV] AUC 367 [33] ng*h/mL) well below levels observed following TDF-containing regimens Huhn GD, JAIDS 2017; 74:193.200 GS-US-292-0119
GS-US-292-0119 Study: switch to E/C/F/TAF + DRV Efficacy and Safety Results Virologic outcome at W48 HIV RNA < 50 c/mL (ITT, snapshot) E/C/F/TAF + DRV Baseline regimen E/C/F/TAF + DRV Baseline regimen W24 W48 HIV RNA < 20 c/mL 90% 72% (p = 0.012) % 97 100 M184V + K65R in 1 patient on RAL + ETR + DRV/r with BL PI-R and NRTI-R (3 TAMs) and history of TDF + FTC 94 * Emergence of resistance mutations 91 0 76 80 60 Safety, % 40 Baseline regimen E/C/F/TAF + DRV 20 Study-drug related AE 15 0 AEs leading to discontinuation 0 0 0 (95% IC) 18,3 (3.5 ; 33.0) p = 0.004 (95% IC) 5,3 (- 3.4 ; 17.4) Grade 3-4 adverse events study-drug related 13 1 13 0 Serious adverse events study-drug related 10 0 2 0 * 91% if prior DRV/r dose 800 QD vs 100% if prior DRV/r dose 600/100 BID Grade 3-4 lab. abnormalities 11 9 Huhn GD, JAIDS 2017; 74:193.200 GS-US-292-0119
GS-US-292-0119 Study: switch to E/C/F/TAF + DRV Conclusion Simplifying therapy from ~5 pills/day to once-daily, 2-pill E/C/F/TAF + DRV Provided efficacious plasma exposures of EVG, DRV, and TAF Maintained virologic suppression through Week 24 Was superior to staying on baseline regimen at Week 48 at both < 50 and < 20 c/mL Switch to TAF improved proximal tubular proteinuria without change in eGFR E/C/F/TAF + DRV was safe, well tolerated, and associated with greater treatment satisfaction For treatment-experienced individuals with 2 class resistance on complex, high-pill burden regimens, switching to E/C/F/TAF + DRV provides a simple, once-daily, two-pill option with superior efficacy and comparable tolerability Huhn GD, JAIDS 2017; 74:193.200 GS-US-292-0119
