Rilpivirine vs Efavirenz for a Viral Load Under 100,000
Rilpivirine vs Efavirenz for a Viral Load Under 100,000
ECHO (TMC278-C209; NCT00540449) and THRIVE (TMC278-C215; NCT00543725) were phase 3, randomized, double-blind, double-dummy, active-controlled, international trials. The design and methodology of these trials have been reported previously. The primary objective of ECHO and THRIVE was to demonstrate the noninferiority, as assessed by response rates (viral load < 50 copies/mL), of rilpivirine vs. efavirenz at week 48 using an ITT population and a TLOVR imputation algorithm.
The trials enrolled antiretroviral treatment-naïve, HIV-1-infected adults with baseline viral load ≥ 5000 copies/mL, confirmed viral sensitivity to the background nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) and no documented evidence of NNRTI resistance.
Patients were randomized 1:1 to receive rilpivirine 25 mg with efavirenz placebo once daily, or efavirenz 600 mg with rilpivirine placebo once daily. In ECHO, patients received a fixed N[t]RTI background regimen of tenofovir disoproxil fumarate and emtricitabine. In THRIVE, patients received an investigator-chosen N[t]RTI background regimen of tenofovir disoproxil fumarate/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine. Randomization was stratified by background regimen (THRIVE) and screening viral load (≤ 100 000 copies/mL, 100 001–500 000 copies/mL and > 500 000 copies/mL).
Resistance analyses of the 96-week database were performed on the pooled ITT ECHO/THRIVE populations. Virological failure for the resistance analysis (VFres) was defined as either: (1) first achieving two consecutive viral load values < 50 copies/mL then having two consecutive (or only one if treatment was stopped) viral load values ≥ 50 copies/mL (rebounder); or (2) never achieving two consecutive viral load values < 50 copies/mL and having an increase in viral load ≥ 0.5 log10 copies/mL above the nadir (never suppressed).
Safety and tolerability were assessed throughout the trials. Laboratory parameters and changes in plasma lipids were also assessed.
Only statistical comparisons between treatment groups that were preplanned for specific AEs and lipid measurements for the overall population are presented for this 96-week analysis of data for the pooled ECHO/THRIVE population with baseline viral load ≤ 100 000 copies/mL. For statistical comparison of AEs, Fisher's exact test (5% significance level) was used. For statistical comparison of lipids, the Wilcoxon rank-sum test was used.
Methods
ECHO (TMC278-C209; NCT00540449) and THRIVE (TMC278-C215; NCT00543725) were phase 3, randomized, double-blind, double-dummy, active-controlled, international trials. The design and methodology of these trials have been reported previously. The primary objective of ECHO and THRIVE was to demonstrate the noninferiority, as assessed by response rates (viral load < 50 copies/mL), of rilpivirine vs. efavirenz at week 48 using an ITT population and a TLOVR imputation algorithm.
The trials enrolled antiretroviral treatment-naïve, HIV-1-infected adults with baseline viral load ≥ 5000 copies/mL, confirmed viral sensitivity to the background nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) and no documented evidence of NNRTI resistance.
Patients were randomized 1:1 to receive rilpivirine 25 mg with efavirenz placebo once daily, or efavirenz 600 mg with rilpivirine placebo once daily. In ECHO, patients received a fixed N[t]RTI background regimen of tenofovir disoproxil fumarate and emtricitabine. In THRIVE, patients received an investigator-chosen N[t]RTI background regimen of tenofovir disoproxil fumarate/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine. Randomization was stratified by background regimen (THRIVE) and screening viral load (≤ 100 000 copies/mL, 100 001–500 000 copies/mL and > 500 000 copies/mL).
Resistance analyses of the 96-week database were performed on the pooled ITT ECHO/THRIVE populations. Virological failure for the resistance analysis (VFres) was defined as either: (1) first achieving two consecutive viral load values < 50 copies/mL then having two consecutive (or only one if treatment was stopped) viral load values ≥ 50 copies/mL (rebounder); or (2) never achieving two consecutive viral load values < 50 copies/mL and having an increase in viral load ≥ 0.5 log10 copies/mL above the nadir (never suppressed).
Safety and tolerability were assessed throughout the trials. Laboratory parameters and changes in plasma lipids were also assessed.
Only statistical comparisons between treatment groups that were preplanned for specific AEs and lipid measurements for the overall population are presented for this 96-week analysis of data for the pooled ECHO/THRIVE population with baseline viral load ≤ 100 000 copies/mL. For statistical comparison of AEs, Fisher's exact test (5% significance level) was used. For statistical comparison of lipids, the Wilcoxon rank-sum test was used.