Maraviroc is the first in a new class of antiretrovirals called CCR5 antagonists. Maraviroc blocks the interaction between HIV-1 and the CCR5 chemokine co-receptor on the CD4 T-cell membrane, preventing the virus from entering T-cells.
It is effective only against those strains of HIV-1 that are CCR5-tropic (i.e. use the CCR5 co-receptor to gain entry to cells). Maraviroc is not active against viruses which use CXCR4 as their entry co-receptor. Therefore, tropism testing should be done prior to starting treatment to ensure that CXCR4 or dual/mixed-tropic viruses are not detected.
The efficacy of maraviroc has been evaluated in two ongoing trials (MOTIVATE 1 and 2, n=1076). At study entry, patients with CCR5-tropic HIV-1 infection had a viral load of >5,000 copies/ml with prior exposure to at least one agent from three classes of antiretrovirals, or resistance or intolerance to at least one member of each drug class.
Patients were placed on an optimised background therapy (OBT) regimen with three to six antiretrovirals, and then randomised to receive maraviroc 300mg once daily, maraviroc 300mg twice daily or placebo. The dose of maraviroc was adjusted depending on co-administered medication and the results for the licensed twice-daily regimen are given below.
Pooled analysis1 after 48 weeks showed that maraviroc plus OBT was superior to placebo plus OBT in achieving undetectable viral load (<50 copies/ml); 45.5 per cent in the maraviroc arm, compared with 16.7 per cent for placebo. Mean change from baseline in CD4 cell count was 124.07 cells/mm3 in the maraviroc arm, compared to 60.93 cells/mm3 for placebo. There were no clinically relevant differences in the safety profile between the treatment groups.
1. Celsentri Summary of Product Characteristics, 17th September 2007; Pfizer.