DOWNLOAD THIS SLIDE KIT

ECHO Study: RPV + TDF/FTC QD vs EFV + TDF/FTC QD

Design :

* 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)

Baseline characteristics and patient disposition :

Response to treatment at week 48 :

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])

Mean CD4/mm3 increase at W48 :
+ 196 (RPV + TDF/FTC) vs
+ 182 (EFV + TDF/FTC), p = 0.13

Virologic response to treatment at week 48 by subgroups :

Virologic failure definition :

• Never suppressed : never achieved 2 consecutive HIV RNA < 50 c/mL and increaseof 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 resistance testing :

• All virological failures

Treatment-emergent adverse events :

Adverse events of interest of any grade :

Grade 3-4 laboratory abnormalities :

Mean (95% CI) change in fasting lipids from baseline to week 48 :

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

THRIVE Study: RPV + 2 NRTI vs EFV + 2 NRTI

Design :

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)

Baseline characteristics and patient disposition :

Response to treatment at week 48 :

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])

Mean CD4/mm3 increase at W48 :
+ 189 (RPV + 2 NRTI) vs
+ 171 (EFV + 2 NRTI), P = 0.09

Virologic response to treatment at week 48 by subgroups :

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 resistance testing :

• All virological failures

Treatment-emergent adverse events :

Adverse events of interest of any grade, n (% of patients) :

Grade 3-4 laboratory abnormalities :

Mean (95% CI) change in fasting lipids from baseline to week 48 :

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

ECHO & THRIVE Study: W96 results

Response to treatment at week 96 :

* TDF/FTC = 80%, ZDV/3TC = 15%, ABC/3TC = 5%

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])

Discontinuation by 96 weeks (RPV vs EFV)
- For virologic endpoint : 8% vs 3%
- For adverse events : 4% vs 9%

Virologic response to treatment at week 96 by subgroups :

*Randomisation was stratified by clinical site and by HIV RNA (< or > 100,000 c/mL) at screening

• Non inferiority of EFV 400 mg at W48: % HIV RNA < 200 c/mL by modified intention to treat analysis (all randomised participants who received at least 1 dose of study drug and at least one follow-up visit), 2-sided significance level of 5%, lower margin of the 95% CI for the difference = -10%, 90% power

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

Adverse events and treatment-emergent grade 2-4 laboratory abnormalities :