Lersivirine — a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) from the class of efavirenz (Sustiva^®) nevirapine (Viramune^®), rilpivirine (Edurant®)and etravirine (Intelence^®)— has shown promise in early clinical trials, but its comparative efficacy has not been established. In a manufacturer-sponsored, placebo-controlled, double-blind, phase IIb, dose-seeking study, 195 HIV-infected adults with viral loads 1000 copies/mL and CD4 counts 200 cells/mm3 were randomized to receive tenofovir/FTC plus either lersivirine (500 or 750 mg once daily) or efavirenz (600 mg once daily). In a modified intent-to-treat analysis, the proportion of patients with viral loads <50 copies/mL at week 48 was 78.5% in both lersivirine arms and 85.7% in the efavirenz group. Virologic failure was somewhat more common with lersivirine, but efavirenz had a slightly higher adverse-event rate.

Comment: Lersivirine is a novel NNRTI with a unique resistance pattern, broad cross-clade activity, and a promising adverse-event profile. Although the current study was not adequately powered to assess noninferiority to efavirenz, the results in all three arms were similar enough to justify large-scale, appropriately powered studies of lersivirine. Unfortunately, the makers of the drug have decided not to pursue further development, so trials to determine the drug’s true safety and efficacy will not take place.

CITATION: Vernazza P et al. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment–naive HIV-1–infected patients: Week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J Acquir Immune Defic Syndr 2013 Feb 1; 62:171.

Published in Journal Watch HIV/AIDS Clinical Care