Maraviroc for previously treated patients with R5 HIV-1 infection
Por:
Gulick, RM, Lalezari, J, Goodrich, J, Clumeck, N, DeJesus, E, Horban, A, Nadler, J, Clotet, B, Karlsson, A, Wohlfeiler, M, Montana, JB, McHale, M, Sullivan, J, Ridgway, C, Felstead, S, Dunne, MW, van der Ryst, E and Mayer, H
Publicada:
2 oct 2008
Categoría:
Medicine (miscellaneous)
Resumen:
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 log(10) 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 log(10) 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. (ClinicalTrials. gov numbers, NCT00098306 and NCT00098722.).
Filiaciones:
Gulick, RM:
Weill Cornell Med Coll, New York, NY 10065 USA
Lalezari, J:
Quest Clin Res, San Francisco, CA USA
Univ Calif San Francisco, Mt Zion Hosp, San Francisco, CA 94143 USA
Goodrich, J:
Pfizer Global Res & Dev, New London, CT USA
Clumeck, N:
Ctr Hosp Univ St Pierre, Brussels, Belgium
DeJesus, E:
Orlando Immunol Ctr, Orlando, FL USA
Horban, A:
Wojewodzki Szpital Zakazny, Warsaw, Poland
Nadler, J:
Univ S Florida, Coll Med, Tampa, FL USA
:
Fdn Irsicaixa, Badalona, Spain
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
Karlsson, A:
Karolinska Univ Hosp, Stockholm, Sweden
Wohlfeiler, M:
Wohlfeiler Piperato & Assoc, N Miami Beach, FL USA
McHale, M:
Pfizer Global Res & Dev, Sandwich, Kent, England
Sullivan, J:
Pfizer Global Res & Dev, Sandwich, Kent, England
Ridgway, C:
Pfizer Global Res & Dev, Sandwich, Kent, England
Felstead, S:
Pfizer Global Res & Dev, Sandwich, Kent, England
Dunne, MW:
Pfizer Global Res & Dev, New London, CT USA
van der Ryst, E:
Pfizer Global Res & Dev, Sandwich, Kent, England
Mayer, H:
Pfizer Global Res & Dev, New London, CT USA
Green Accepted
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