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Maraviroc Once-Daily Nucleoside Analog-Sparing Regimen in Treatment-Naive Patients: Randomized, Open-Label Pilot Study

Mills, Anthony MD*; Mildvan, Donna MD; Podzamczer, Daniel MD, PhD; Fätkenheuer, Gerd MD§; Leal, Manuel MD, PhD; Than, Soe MD, PhD; Valluri, Srinivas R. PhD#; Craig, Charles PhD**; McFadyen, Lynn PhD**; Vourvahis, Manoli PharmD#; Heera, Jayvant MD, MFPM; Valdez, Hernan MD#; Rinehart, Alex R. PhD††; Portsmouth, Simon MD, FRCP#

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2013 - Volume 62 - Issue 2 - p 164–170
doi: 10.1097/QAI.0b013e31827b51b5
Clinical Science

Objective: This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients.

Design: A phase 2b, randomized, open-label pilot study.

Methods: In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm3) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48.

Results: At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed.

Conclusions: The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.

Supplemental Digital Content is Available in the Text.

*Anthony Mills MD Inc., Los Angeles, CA

Division of Infectious Diseases, Beth Israel Medical Center, New York, NY

HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain

§First Department of Internal Medicine, University Hospital of Cologne, Köln, Germany

Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Infectious Disease Service, Virgen del Rocio University Hospital, Seville, Spain

¶ Medicines development group, Pfizer Inc, Groton, CT

#Medicines development group, Pfizer Inc, New York, NY

**Medicines development group, Pfizer Inc, Sandwich, Kent, United Kingdom

††Research and Development, ViiV Healthcare, Research Triangle Park, NC.

Correspondence to: Simon Portsmouth, MD, FRCP, Mail stop 219-08-02, Pfizer Inc, 235 East 42nd Street, New York, NY 10017 (e-mail: simon.portsmouth@pfizer.com).

Presented at the International AIDS Society—6th Conference on HIV Pathogenesis, Treatment & Prevention, July 17–20, 2011, Rome.

Supported by ViiV Healthcare.

A. Mills has acted as a consultant for Gilead and Janssen; has received payment for lectures (including service on speaker’s bureau) from Abbott, Gilead, Janssen, and Merck; and has received research grants from Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer Inc, and ViiV Healthcare. D. Mildvan has received research grants from Pfizer Inc, and travel/accommodation/meeting expenses unrelated to the activities listed from Pfizer Inc. D. Podzamczer has acted as a consultant and provided expert testimony for, has received research grants and payment for lectures (including service on speaker’s bureau) from Boehringer Ingelheim, GSK, ViiV Healthcare, Pfizer Inc, BMS, Abbott, Gilead, Janssen, and Merck, and has received travel/accommodation/meeting expenses unrelated to activities listed from Boehringer Ingelheim. G. Fätkenheuer has acted as a consultant for Abbott, Boehringer Ingelheim, MSD, Janssen, Gilead, and ViiV Healthcare; and has received payment for lectures (including service on speaker’s bureau) from Abbott, BMS, Boehringer Ingelheim, Gilead, Janssen, ViiV Healthcare, MSD, Pfizer Inc, and Roche. M. Leal has received research grants from Pfizer Inc. S. R. Valluri, L. McFadyen, M. Vourvahis, J. Heera, H. Valdez, S. Than, and S. Portsmouth are employees of Pfizer Inc, and hold stock/stock options in Pfizer Inc. A. R. Rinehart is an employee of ViiV Healthcare and holds stock/stock options in ViiV Healthcare. C. Craig is a former employee of Pfizer Inc, and holds stock/stock options in Pfizer Inc.

The authors have no other conflicts of interest to disclose.

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 (www.jaids.com).

Received March 21, 2012

Accepted October 26, 2012

© 2013 Lippincott Williams & Wilkins, Inc.