Journal article
Maraviroc for Previously Treated Patients with R5 HIV-1 Infection
The New England journal of medicine, Vol.359(14), pp.1429-1441
2008
DOI: 10.1056/NEJMoa0803152
PMCID: PMC3078519
PMID: 18832244
Abstract
BACKGROUND
CC chemokine receptor 5 antagonists are a new class of antiretroviral agents.
METHODS
We conducted two double-blind, placebo-controlled, phase 3 studies — Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 — with patients who had R5 human immunodeficiency virus type 1 (HIV-1) only. They had been treated with or had resistance to three antiretroviral-drug classes and had HIV-1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy (OBT) based on treatment history and drug-resistance testing. Safety and efficacy were assessed after 48 weeks.
RESULTS
A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater with maraviroc than with placebo: –1.66 and –1.82 log10 copies per milliliter with the once-daily and twice-daily regimens, respectively, versus –0.80 with placebo in MOTIVATE 1, and –1.72 and –1.87 log10 copies per milliliter, respectively, versus –0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P<0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo (increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P<0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups.
CONCLUSIONS
Maraviroc, as compared with placebo, resulted in significantly greater suppression of HIV-1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV-1 who were receiving OBT.
Details
- Title: Subtitle
- Maraviroc for Previously Treated Patients with R5 HIV-1 Infection
- Creators
- Roy M GULICK - Weill-Cornell Medical College, New York, United StatesJacob LALEZARI - Quest Clinical Research and Mount Zion Hospital of the University of California, San Francisco, San Francisco, United StatesJohn B MONTANA - Weill-Cornell Medical College, New York, United StatesMary MCHALE - Pfizer Global Research and Development, Sandwich, United KingdomJohn SULLIVAN - Pfizer Global Research and Development, Sandwich, United KingdomCaroline RIDGWAY - Pfizer Global Research and Development, Sandwich, United KingdomSteve FELSTEAD - Pfizer Global Research and Development, Sandwich, United KingdomMichael W DUNNE - Pfizer Global Research and Development, New London, CT, United StatesElna VAN DER RYST - Pfizer Global Research and Development, Sandwich, United KingdomHoward MAYER - Pfizer Global Research and Development, New London, CT, United StatesJames GOODRICH - Pfizer Global Research and Development, New London, CT, United StatesNathan CLUMECK - Centre Hospitalier Universitaire St-Pierre, Brussels, BelgiumEdwin DEJESUS - Orlando Immunology Center, Orlando, FL, United StatesAndrzej HORBAN - Wojewodzki Szpital Zakazny, Warsaw, PolandJeffrey NADLER - University of South Florida, College of Medicine, Tampa, United StatesBonaventura CLOTET - Fundacio Irsicaixa and Hospital Universitari Germans Trias i Pujol, Badalona, SpainAnders KARLSSON - Venhälsan, Karolinska University Hospital, Stockholm, SwedenMichael WOHLFEILER - Wohlfeiler, Piperato, and Associates, North Miami Beach, FL, United StatesMOTIVATE Study Teams
- Contributors
- Jack T Stapleton (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.359(14), pp.1429-1441
- Publisher
- Massachusetts Medical Society
- DOI
- 10.1056/NEJMoa0803152
- PMID
- 18832244
- PMCID
- PMC3078519
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Language
- English
- Date published
- 2008
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094582002771
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