1 / 23

Comparison of NNRTI vs NNRTI

Comparison of NNRTI vs NNRTI. ENCORE EFV vs RPV ECHO-THRIVE STAR EFV vs ETR SENSE DOR vs EFV DRIVE-AHEAD. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD. Design. Randomisation* 1 : 1 Double-blind. W48. W96. > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count

loe
Download Presentation

Comparison of NNRTI vs NNRTI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Comparison of NNRTI vs NNRTI • ENCORE • EFV vs RPV • ECHO-THRIVE • STAR • EFV vs ETR • SENSE • DOR vs EFV • DRIVE-AHEAD

  2. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD • Design Randomisation* 1 : 1 Double-blind W48 W96 > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count eGFR> 50 mL/min No R to TDF or FTC No NNRTI resistance mutations No HIV-2 infection N = 346 N =348 * Randomisation was stratified by HIV RNA (< or > 100,000 c/mL, < 500,000 or > 500,000 c/mL ) at screening RPV taken with meal, EFV taken on an empty stomach in the evening • Objective • Non inferiority of RPV vs EFV at W48: % HIV RNA < 50 c/mL by intention to treat, TLOVR analysis (lower margin of the 2-sided 95% CIfor the difference = 12%, 95% power) Molina JM. Lancet 2011;378:238:46 ECHO

  3. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD Baseline characteristics and patient disposition Molina JM. Lancet 2011;378:238:46 ECHO

  4. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD Response to treatment at week 48 HIV RNA < 50 c/mL RPV + TDF/FTC % EFV + TDF/FTC Primaryanalysis 100 84 83 83 83 ITT-TLOVR censoring for non-virologic failure, HIV RNA < 50 c/mL : • RPV + TDF/FTC = 86% • EFV + TDF/FTC = 94% (difference : -7.9% [95% CI : -12.5 ; -3.3]) 75 50 25 Mean CD4/mm3 increase at W48 : • + 196 (RPV + TDF/FTC) vs • + 182 (EFV + TDF/FTC), p = 0.13 0 ITT, TLOVR Per protocol, TLOVR Adjusted difference from logistic-regression model (95% CI)= - 0.4% (- 5.9 ; 5.2) Adjusted difference (95% CI)= 0.8 % (- 4.8 ; 6.5) Molina JM. Lancet 2011;378:238:46 ECHO

  5. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD Virologic response to treatment at week 48 by subgroups HIV RNA < 50 c/mL (ITT, TLOVR) according to baseline HIV RNA HIV RNA < 50 c/mL (ITT, TLOVR) according to adherence rate RPV + TDF/FTC EFV + TDF/FTC % % 90 100 100 87 86 83 83 81 79 73 68 75 75 62 50 50 25 25 0 0 181 163 131 134 34 47 275 262 44 56 < 100,000 c/mL 100,000-500,000 c/mL > 500,000 c/mL Adherence > 95% Adherence < 95% Molina JM. Lancet 2011;378:238:46 ECHO

  6. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD • Virologic failure definition • Never suppressed : never achieved 2 consecutive HIV RNA < 50 c/mL and increaseof HIV RNA > 0.5 log10c/mL above the nadir • Rebounder : achieved 2 consecutive HIV RNA < 50 c/mL with 2 subsequent consecutive (or 1 if last available) HIV RNA > 50 c/mL • Criteria for resistance testing • All virological failures Resistance data at week 48 Molina JM. Lancet 2011;378:238:46 ECHO

  7. Treatment-emergent adverse events ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD Molina JM. Lancet 2011;378:238:46 ECHO

  8. Adverse events of interest of any grade ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD Molina JM. Lancet 2011;378:238:46 ECHO

  9. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD • Grade 3-4 laboratory abnormalities • Mean (95% CI) change in fasting lipids from baseline to week 48 Molina JM. Lancet 2011;378:238:46 ECHO

  10. ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD • Summary of week 48 results • RPV QD is virologically non inferior to EFV, when given in combination with TDF/FTC • Response rate was lower in the RPV group for patients with highest baseline viral loads • Discontinuation because of virologic failure was higher for RPV, and discontinuation because of adverse events was higher for EFV • Proportion of virological failures with • > 1 emergent NNRTI resistance-associated mutation : similar in both groups • Most frequent mutations on RPV lead to NNRTI cross resistance • At EFV failure, K103 N was the most frequent mutation, with conserved sensitivity to etravirine • > 1 emergent NRTI resistance mutation : higher in the RPV group • More favorable overall safety profile of RPV than EFV : lower rate of • grade 2-4 AE possibly related to treatment • rash • neurological and psychiatric adverse events • increases in proatherogenic lipid parameters Molina JM. Lancet 2011;378:238:46 ECHO

  11. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI • Design Randomisation 1 : 1 Double-blind W48 W96 > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count eGFR> 50 mL/min No R to background NtRTI No NNRTI resistance mutations No HIV-2 infection N = 340 N = 340 Randomisation was stratified by HIV RNA (< or > 100,000 c/mL, < 500,000 or > 500,000 c/mL ) at screening * Open-label NRTI combination selected by investigator : ZDV+3TC BID or ABC+3TC QD or TDF+FTC QD • Objective • Non inferiority of RPV vs EFV at W48: % HIV RNA < 50 c/mL by intention to treat, TLOVR analysis (lower margin of the 2-sided 95% CI for the difference = 12%, 95% power) Cohen CJ. Lancet 2011;378:229-37 THRIVE

  12. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Baseline characteristics and patient disposition Cohen CJ. Lancet 2011;378:229-37 THRIVE

  13. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Response to treatment at week 48 HIV RNA < 50 c/mL RPV + 2 NRTI % EFV + 2 NRTI Primaryanalysis 100 86 86 82 82 ITT-TLOVR censoring for non-virologic failure, % HIV RNA < 50 c/mL : • RPV + 2 NRTI = 91% • EFV + 2 NRTI = 94% (difference : -2.0% [95% CI : - 6.3 ; 2.2]) 75 50 25 Mean CD4/mm3 increase at W48 : • + 189 (RPV + 2 NRTI) vs • + 171 (EFV + 2 NRTI), P = 0.09 0 ITT, TLOVR Per protocol, TLOVR Adjusted difference from logistic-regression model (95% CI)= 3.5% (- 1.7 ; 8.8) Adjusted difference (95% CI)= 3.7 % (- 1.9 ; 9.3) Cohen CJ. Lancet 2011;378:229-37 THRIVE

  14. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Virologic response to treatment at week 48 by subgroups HIV RNA < 50 c/mL (ITT, TLOVR) according to baseline HIV RNA HIV RNA < 50 c/mL (ITT, TLOVR) according to adherence rate RPV + 2 NRTI EFV + 2 NRTI % % 91 100 100 90 89 84 82 80 77 69 75 75 64 62 50 50 25 25 0 0 187 167 118 136 35 35 272 230 36 39 < 100,000 c/mL 100,000-500,000 c/mL > 500,000 c/mL Adherence > 95% Adherence < 95% Cohen CJ. Lancet 2011;378:229-37 THRIVE

  15. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI • Virologic failure definition • Never suppressed : never achieved 2 consecutive HIV RNA < 50 c/mL and increase of HIV RNA > 0.5 log10 c/mL above the nadir • Rebounder : achieved 2 consecutive HIV RNA < 50 c/mL with 2 subsequent consecutive (or 1 if last available) HIV RNA > 50 c/mL • Criteria for resistancetesting • All virologicalfailures Resistance data at week 48 Cohen CJ. Lancet 2011;378:229-37 THRIVE

  16. Treatment-emergent adverse events THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Cohen CJ. Lancet 2011;378:229-37 THRIVE

  17. Adverse events of interest of any grade, n (% of patients) THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Cohen CJ. Lancet 2011;378:229-37 THRIVE

  18. THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI • Grade 3-4 laboratoryabnormalities • Mean (95% CI) change in fasting lipids from baseline to week 48 Cohen CJ. Lancet 2011;378:229-37 THRIVE

  19. Summary of week 48 results RPV QD is virologically non inferior to EFV, when given in combination with 2 NRTI Response rates seemed highest in the RPV group for patients with lowest baseline viral loads Background NRTI regimen had no significant effect on responses (limitation : no randomisation, no stratification by NRTI) Discontinuation because of adverse events or other reasons was lower for RPV Proportion of virological failures with > 1 emergent NNRTI resistance-associated mutation : similar in both groups, > 1 emergent NRTI resistance mutation : higher in the RPV group More favorable overall safety profile of RPV than EFV : lower rate of grade 2-4 AE possibly related to treatment rash dizziness increases in proatherogenic lipid parameters THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI Cohen CJ. Lancet 2011;378:229-37 THRIVE

  20. ECHO & THRIVE Study: W96 results Response to treatment at week 96 HIV RNA < 50 c/mL RPV + 2 NRTI* % EFV + 2 NRTI* Primaryanalysis * TDF/FTC = 80%, ZDV/3TC = 15%, ABC/3TC = 5% 100 79 78 78 78 ITT-TLOVR censoring for non-virologic failure, % HIV RNA < 50 c/mL : • RPV + 2 NRTI = 85% • EFV + 2 NRTI = 91% (difference : - 6.2% [95% CI : - 9.9 ; - 2.5]) 75 50 Discontinuation by 96 weeks (RPV vs EFV) • For virologic endpoint : 8% vs 3% • For adverse events : 4% vs 9% 25 0 ITT, TLOVR Per protocol, TLOVR Adjusted difference from logistic-regression model (95% CI)= - 0.4% (- 4.6 ; 3.8) Adjusted difference (95% CI)= 0.4 % (- 4.0 ; 4.9) Cohen CJ. AIDS 2013;27:939-50 ECHO-THRIVE

  21. ECHO & THRIVE Study: W96 results Virologic response to treatment at week 96 by subgroups HIV RNA < 50 c/mL (ITT, TLOVR) according to baseline HIV RNA HIV RNA < 50 c/mL (ITT, TLOVR) according to adherence rate RPV + 2 NRTI EFV + 2 NRTI % % 100 100 84 84 81 80 76 73 71 75 75 65 65 56 50 50 25 25 0 0 368 329 249 270 69 83 552 499 87 100 < 100,000 c/mL 100,000-500,000 c/mL > 500,000 c/mL Adherence > 95% Adherence < 95% Cohen CJ. AIDS 2013;27:939-50 ECHO-THRIVE

  22. ECHO & THRIVE Study: W96 results Resistance data at week 96 • The majority of virologic failures occurred in the first 48 weeks (76% in the RPV group and 69% in the EFV group) • Virologic failure and treatment-emergent RT mutations were similar at low baseline viral load but more frequent at high baseline viral load in RPV-treated than in EFV-treated patients Cohen CJ. AIDS 2013;27:939-50 ; Rimsky L. JAIDS 2012;59:39-46 ; Rimsky L. AntivirTher 2013;18:967-77 ECHO-THRIVE

  23. Adverse events and treatment-emergent grade 2-4 laboratory abnormalities ECHO & THRIVE Study: W96 results Cohen CJ. AIDS 2013;27:939-50 ECHO-THRIVE

More Related