TY - JOUR
T1 - Maraviroc for previously treated patients with R5 HIV-1 infection
AU - Gulick, Roy M.
AU - Lalezari, Jacob
AU - Goodrich, James
AU - Clumeck, Nathan
AU - DeJesus, Edwin
AU - Horban, Andrzej
AU - Nadler, Jeffrey
AU - Clotet, Bonaventura
AU - Karlsson, Anders
AU - Wohlfeiler, Michael
AU - Montana, John B.
AU - McHale, Mary
AU - Sullivan, John
AU - Ridgway, Caroline
AU - Felstead, Steve
AU - Dunne, Michael W.
AU - van der Ryst, Elna
AU - Mayer, Howard
AU - AUTHOR GROUP
AU - Angel, Jonathan
AU - Conway, Brian
AU - Gough, Kevin A.
AU - Lalonde, Richard G.
AU - Laplante, Francois
AU - Leblanc, Roger P.
AU - Montaner, Julio S. G.
AU - Rachlis, Anita R.
AU - Romanowski, Barbara
AU - Rosser, Stuart J.
AU - Rubinstein, Ethan
AU - Shafran, Stephen David
AU - Smaill, Fiona
AU - Tremblay, Cecile
AU - Trottier, Benoit
AU - Trottier, Sylvie
AU - Tsoukas, Christos
AU - Walmsley, Sharon Lynn
AU - Voskanian, Alen
AU - Akil, Bisher
AU - Arduino, Roberto Claudio
AU - Asmuth, David
AU - Beatty, George William
AU - Becker, Stephen Lawrence
AU - Bellos, Nicholaos C.
AU - Blue, Sky Robert
AU - Bolan, Robert Key
AU - Brand, John D.
AU - Burnazian, George Ghazaros
AU - Burnside, Alfred F.
AU - Campbell, Thomas B.
AU - Prins, J. M.
PY - 2008
Y1 - 2008
N2 - 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.)
AB - 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.)
U2 - https://doi.org/10.1056/NEJMoa0803152
DO - https://doi.org/10.1056/NEJMoa0803152
M3 - Article
C2 - 18832244
SN - 0028-4793
VL - 359
SP - 1429
EP - 1441
JO - New England journal of medicine
JF - New England journal of medicine
IS - 14
ER -