Efficacy and Safety of Lersivirine (UK-453,061) versus Efavirenz in Antiretroviral Treatment-Naïve HIV-1-Infected Patients: Week 48 Primary Analysis Results from an Ongoing, Multicenter, Randomized, Double-Blind, Phase IIb Trial

Publication

Efficacy and Safety of Lersivirine (UK-453,061) versus Efavirenz in Antiretroviral Treatment-Naïve HIV-1-Infected Patients: Week 48 Primary Analysis Results from an Ongoing, Multicenter, Randomized, Double-Blind, Phase IIb Trial

Journal Paper/Review - Oct 31, 2012

Vernazza Pietro, Craig Charles, Mori Julie, Goodrich James, Valdez Hernan, Lazzarin Adriano, Kaplan Richard, Cooper David A, Pulik Piotr, Weil Elizabeth, Pozniak Anton, Wang Cunshan, Tawadrous Margaret

Citation

Vernazza P, Craig C, Mori J, Goodrich J, Valdez H, Lazzarin A, Kaplan R, Cooper D, Pulik P, Weil E, Pozniak A, Wang C, Tawadrous M. Efficacy and Safety of Lersivirine (UK-453,061) versus Efavirenz in Antiretroviral Treatment-Naïve HIV-1-Infected Patients: Week 48 Primary Analysis Results from an Ongoing, Multicenter, Randomized, Double-Blind, Phase IIb Trial. J Acquir Immune Defic Syndr 2012

Type

Journal Paper/Review (English)

Journal

J Acquir Immune Defic Syndr 2012

Publication Date

Oct 31, 2012

Issn Electronic

1944-7884

Brief description/objective

OBJECTIVE:: A 96-week clinical study was planned to estimate the antiviral activity and safety of lersivirine in treatment-naïve HIV-1-infected patients. METHODS:: This ongoing international, multicenter, double-blind, randomized, Phase IIb exploratory study evaluates the efficacy and safety of two doses of lersivirine or one of efavirenz, each combined with tenofovir disoproxil fumarate (DF)/emtricitabine. Patients were randomized 1:1:1 to receive lersivirine (500 or 750 mg once-daily [QD]) or efavirenz (600 mg QD), each administered with tenofovir DF/emtricitabine (300 mg/200 mg QD). The primary endpoint is the proportion of patients with HIV-1 RNA <50 copies/mL (missing/discontinuation=failure) at Week 48. RESULTS:: For the 193 patients in the study, baseline mean plasma HIV-1 RNA was 4.7 log10 copies/mL, and median CD4 cell count was 312 cells/mm. At Week 48, the percentage of patients with HIV-1 RNA <50 copies/mL 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 seven patients (11%) in each of the lersivirine groups and three patients (5%) in the efavirenz group. The pattern of lersivirine resistance was distinct from other non-nucleoside 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. CONCLUSIONS:: Both lersivirine doses showed broadly comparable efficacy to efavirenz over 48 weeks in treatment-naïve patients, with different AE profiles from efavirenz.