Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials

Abstract

Objectives: These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.

Methods: ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen. Response rate (the percentage of patients with VL < 50 copies/mL, using an intent-to-treat-population, time-to-loss-of-virological-response algorithm), virological failure (VF), resistance development, safety and tolerability were evaluated.

Results: Baseline characteristics were comparable between the rilpivirine (n = 368) and efavirenz (n = 329) groups. At week 96, response rates [84% for rilpivirine vs. 80% for efavirenz; difference 4.0%; 95% confidence interval (CI) -1.7% to 9.7%] and incidences of VF for the resistance analysis (VFres) (8% for rilpivirine vs. 6% for efavirenz; P = 0.46) were similar in the two groups. Among patients with VFres , a comparable proportion in each group developed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). Among those with VFres , more patients in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs, mostly M184I/V. The mean (95% CI) CD4 cell count increased from baseline to week 96 by 224 (208-240) cells/μL in the rilpivirine group and by 206 (188-225) cells/μL in the efavirenz group. Treatment-related grade 2-4 overall adverse events, any rash and dizziness were less frequent for rilpivirine than for efavirenz (P < 0.0001).

Conclusions: Rilpivirine demonstrated antiviral efficacy similar to that of efavirenz in antiretroviral treatment-naïve adults with baseline VL ≤ 100 000 copies/mL over 96 weeks. Frequencies of VFres and emergent NNRTI RAMs in each group were similar. More patients with VFres in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs (mostly M184I/V). Rilpivirine had a more favourable safety/tolerability profile than efavirenz.

Keywords: TMC278; baseline viral load; efavirenz; nonnucleoside reverse transcriptase inhibitor; rilpivirine; treatment-naïve.