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Home > Treatment > HIV Meds Quarterly > Summer 2011 > Lersivirine
Lersivirine: A New NNRTI

Lersivirine (UK-453,061) is an investigational second-generation NNRTI that (in in vitro studies) is active against many HIV strains with NNRTI resistance mutations. At the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Rome this summer, researchers presented data on a multicenter Phase 2b study of lersivirine in treatment-naive individuals. Subjects (n = 193) were randomized to 1 of 2 dosages of lersivirine (500 mg QD or 750 mg QD) or to efavirenz, each in combination with tenofovir/emtricitabine. Mean baseline HIV RNA was 4.7 log10 copies/mL (one third of subjects had RNA levels of >100,000 copies/mL), and the median CD4 count was 320 cells/µL.

At 48 weeks, 79% of subjects in each of the lersivirine groups had HIV RNA levels of <50 copies/mL, as did 86% of subjects receiving efavirenz. The study was not powered for noninferiority analyses. In subjects with baseline HIV RNA of >100,000 copies/mL, the lersivirine groups had numerically lower overall rates of virologic suppression than the efavirenz group: 75% and 62% of the lersivirine 500 mg and 750 mg groups, respectively, achieved HIV RNA levels of <50 copies/mL through week 48, versus 82% of the efavirenz group. This difference was driven primarily by subjects from South African sites, in whom virologic suppression rates were sharply lower among lersivirine recipients with pretreatment viral loads of >100,000 copies/mL (50% and 38% in the 500 mg and 750 mg groups, respectively, versus 78% among efavirenz recipients); the presenter attributed this to adherence differences involving a small number of subjects (rather than to differences in HIV clade or other factors), but did not provide supporting data. CD4 increases were approximately 190 cells/µL in each treatment group.

Nausea, mostly Grade 1, occurred at higher rates in both lersivirine groups (23% and 42% in the 500 mg and 750 mg groups, respectively) than in the efavirenz group (13%), but neuropsychiatric symptoms and rash were noted more frequently in the efavirenz group. Lersivirine had quite neutral effects on serum lipids, whereas efavirenz increased all lipid parameters.

Clinical bottom line

Larger studies are needed to define more fully the efficacy and tolerability of lersivirine in initial therapy, and to characterize patient groups in which lersivirine would be best suited; Phase 3 studies are under way.


1.Vernazza P, Wang C, Pozniak A, et al. Efficacy and safety of lersivirine (UK-453,061) vs. efavirenz in antiretroviral treatment-naive HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicentre, randomised, double-blind, phase IIb trial (study A5271015). In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome. Abstract TUAB0101.