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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

Vernazza, Pietro MD*; Wang, Cunshan PhD; Pozniak, Anton MD; Weil, Elizabeth MS; Pulik, Piotr MD§; Cooper, David. A. MD; Kaplan, Richard MD; Lazzarin, Adriano MD#; Valdez, Hernan MD**; Goodrich, James PhD, MD††; Mori, Julie PhD‡‡; Craig, Charles PhD‡‡; Tawadrous, Margaret MD, MS

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2013 - Volume 62 - Issue 2 - p 171–179
doi: 10.1097/QAI.0b013e31827a2ba2.
Clinical Science

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.

*Cantonal Hospital, St. Gallen, Switzerland

Pfizer Inc, New London, CT

Chelsea and Westminster Hospital, London, United Kingdom

§Provincial Infectious Hospital of Warsaw, Warsaw, Poland

Kirby Institute, University of New South Wales, Sydney, Australia

Desmond Tutu HIV Foundation, Cape Town, South Africa

#Universita Vita-Salute San Raffaele, Milan, Italy

**Pfizer Inc, New York, NY

††ViiV Healthcare, Research Triangle Park, NC

‡‡Pfizer Global Research and Development, Sandwich Laboratories, Kent, United Kingdom. Julie Mori is now with Retroscreen Virology Ltd, Queen Mary BioEnterprises Innovation Centre, London, United Kingdom.

Correspondence to: Pietro Vernazza, MD, Chefarzt Infektiologie/Spitalhygiene, Cantonal Hospital, Rorschacher Strasse 95, CH-9007 St. Gallen, Switzerland (e-mail: pietro.vernazza@kssg.ch).

This study was conducted by Pfizer Inc and funded by ViiV Healthcare. Editorial support was provided by Dr Bethan Hahn at Complete Medical Communications and funded by ViiV Healthcare.

P. Vernazza has previously been a consultant (with money paid to himself and his institution) for BMS, Gilead Sciences, MSD, Abbott and Janssen Cilag; received payment for lectures from ViiV Healthcare, Janssen Cilag and MSD; and his institution has previously received travel/accommodation/meeting expenses from ViiV Healthcare, Janssen, MSD, BMS, Abbott, Pfizer and Roche.

A. Pozniak receives payment for lectures from ViiV Healthcare, Gilead Sciences and BMS, and travel/accommodation/meeting expenses from BMS and Gilead.

P. Pulik is a board member for BMS and was previously a board member for Janssen Cilag and Roche; is employed by the Hospital for Infectious Diseases, Warsaw, Poland; receives payment for lectures from Boehringer Ingelheim and Roche and has received this previously from BMS and Janssen Cilag; and, along with his institution, received payment from Pfizer Inc for conducting this study.

D. Cooper has received grants and consulting fees from Pfizer Inc, and ViiV Healthcare.

R. Kaplan is employed by the Desmond Tutu HIV Foundation, which was one of the clinical sites where the study took place.

A. Lazzarin receives consulting fees from ViiV Healthcare, Abbott, BMS, and Janssen Cilag; is a board member for BMS and Janssen Cilag; has received payment for lectures from Abbott, Gilead, BMS, and ViiV Healthcare and travel/accommodation/meeting expenses from MSD, Abbott and BMS; and his institution receives grants from Abbott, BMS, ViiV Healthcare, Gilead Sciences and MSD and support for travel to meetings from MSD, BMS and Abbott.

C. Wang, E. Weil, H. Valdez and M. Tawadrous are employees of Pfizer Inc and own stock/stock options in Pfizer Inc. Julie Mori was an employee of Pfizer Inc when the study was conducted and owns stock/stock options in Pfizer Inc.

C. Craig was an employee of Pfizer Inc when the study was conducted, is now employed as a consultant (including travel/accommodations/meeting expenses) to Pfizer Inc, and holds shares in GlaxoSmithKline.

J. Goodrich is an employee of ViiV Healthcare.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (http://www.jaids.com).

Received May 15, 2012

Accepted October 18, 2012

© 2013 Lippincott Williams & Wilkins, Inc.