Rilpivirine vs. efavirenz in HIV-1 patients with baseline viral load 100,000 copies/ml or less: week 48 phase III analysis.

OBJECTIVES: To compare efficacy, resistance development, and safety between rilpivirine and efavirenz in treatment-naive, HIV-1-infected adults with baseline viral load 100,000 copies/ml or less in the pooled 48-week dataset of the ECHO (Efficacy Comparison in treatment-naive HIV-infected subjects Of TMC278 and EFV) and THRIVE (TMC278 against HIV, in a once-daily RegImen Vs. Efavirenz) trials.

DESIGN: Phase III, double-blind, double-dummy, randomized trials.

METHODS: Patients received rilpivirine 25 mg once daily (q.d.) or efavirenz 600 mg q.d. with two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. This analysis considers the subpopulation of 368 rilpivirine and 330 efavirenz patients with baseline viral load 100,000 copies/ml or less.

RESULTS: Significantly higher 48-week response rates (viral load <50 copies/ml, intent-to-treat-time-to-loss-of-virological response) were observed with rilpivirine vs. efavirenz [90 vs. 84%, respectively; difference 6.6% (95% confidence interval 1.6-11.5%)]. The proportion of patients experiencing virological failure (VF(res)) was 5% in each treatment group. A comparable proportion of VF(res) patients in each group developed nonnucleoside reverse transcriptase inhibitor resistance-associated mutations (RAMs) [rilpivirine: 6/16 (38%) vs. efavirenz: 5/12 (42%)]. A numerically higher proportion of rilpivirine VF(res) patients developed N(t)RTI RAMs [7/16 (44%)] vs. efavirenz [2/12 (17%)]; P = 0.2232. A significantly lower incidence for rilpivirine vs. efavirenz was observed for the following events: treatment-related grade 2-4 overall adverse events (17 vs. 30%; P <0.0001), rash (any type; 2 vs. 12%; P <0.0001), and neurological adverse events (19 vs. 40%; P <0.0001), including dizziness (10 vs. 29%; P <0.0001). There was no significant difference between groups in the total cholesterol/high-density lipoprotein cholesterol ratio.

CONCLUSION: In treatment-naive patients with baseline viral load 100,000 copies/ml or less, rilpivirine along with two N(t)RTIs achieved a high response, with a comparable frequency of VF(res) and more favorable tolerability than efavirenz.