Maraviroc for previously treated patients with R5 HIV-1 infection.
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.)
Gulick
Roy M
RM
Weill-Cornell Medical College, New York, NY 10065, USA. rgulick@med.cornell.edu
Lalezari
Jacob
J
Goodrich
James
J
Clumeck
Nathan
N
DeJesus
Edwin
E
Horban
Andrzej
A
Nadler
Jeffrey
J
Clotet
Bonaventura
B
Karlsson
Anders
A
Wohlfeiler
Michael
M
Montana
John B
JB
McHale
Mary
M
Sullivan
John
J
Ridgway
Caroline
C
Felstead
Steve
S
Dunne
Michael W
MW
van der Ryst
Elna
E
Mayer
Howard
H
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D017211:Treatment Failure; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc