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.

A 96-week clinical study was planned to estimate the antiviral activity and safety of lersivirine in treatment-naive HIV-1-infected patients. This ongoing international, multicenter, double-blind, randomized, Phase IIb exploratory study evaluates the efficacy and safety of 2 doses of lersivirine or 1 of efavirenz, each combined with tenofovir disoproxil fumarate/emtricitabine. Patients were randomized 1:1:1 to receive lersivirine (500 or 750 mg once daily) or efavirenz (600 mg once daily), each administered with tenofovir disoproxil fumarate/emtricitabine (300 mg/200 mg, once daily). The primary endpoint is the proportion of patients with HIV-1 RNA <50 copies per milliliter (missing/discontinuation = failure) at week 48. For the 193 patients in the study, baseline mean plasma HIV-1 RNA was 4.7 log10 copies per milliliter, and median CD4 cell count was 312 cells per cubic millimeter. At week 48, the percentage of patients with HIV-1 RNA <50 copies per milliliter was 78.5% (51/65), 78.5% (51/65), and 85.7% (54/63) in the lersivirine 500 mg, 750 mg, and efavirenz groups, respectively. CD4 cell count changes from baseline were similar across groups. Virologic failure occurred in 7 patients (11%) in each of the lersivirine groups and 3 patients (5%) in the efavirenz group. The pattern of lersivirine resistance was distinct from other nonnucleoside reverse transcriptase inhibitors. Overall incidences of all-causality treatment-related or grade 3/4 adverse events (AEs) or AE-related discontinuations were lower with lersivirine than with efavirenz, and serious AEs occurred at similar rates across treatment groups. Both lersivirine doses showed broadly comparable efficacy to efavirenz over 48 weeks in treatment-naive patients, with different AE profiles from efavirenz.