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.
Author(s): Vernazza P(1), Wang C, Pozniak A, Weil E, Pulik P, Cooper DA, Kaplan R, Lazzarin
A, Valdez H, Goodrich J, Mori J, Craig C, Tawadrous M.
Affiliation(s): Author information:
(1)Cantonal Hospital, St. Gallen, Switzerland. pietro.vernazza@kssg.ch
Publication date & source: 2013, J Acquir Immune Defic Syndr. , 62(2):171-9
OBJECTIVE: A 96-week clinical study was planned to estimate the antiviral
activity and safety of lersivirine in treatment-naive HIV-1-infected patients.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Both lersivirine doses showed broadly comparable efficacy to
efavirenz over 48 weeks in treatment-naive patients, with different AE profiles
from efavirenz.
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