FDA has approved a new molecular entity for for use in combination with other antiretroviral agents for the treatment of adults with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
Maraviroc binds selectively to the human chemo-kine receptor CCR5 on cell membranes, thereby blocking the interaction between HIV-1 gp120 and CCR5 that is necessary for CCR5-tropic HIV-1 to enter cells. This agent was approved on August 6, 2007, for use in combination with other antiretroviral agents for the treatment of adults with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
Efficacy. The efficacy of maraviroc was evaluated in analyses of 24-week data from 2 ongoing double-blind, randomized, placebo-controlled, multicenter studies, A4001027 (MOTIVATE-1) and A4001028 (MOTIVATE-2), which enrolled antiretroviral treatment-experienced adult patients with CCR5-tropic HIV-1. An exploratory, randomized, double-blind, multicenter trial, A4001029, was also carried out in antiretroviral treatment-experienced adult patients with dual/mixed-tropic HIV-1. The MOTIVATE-1 and MOTIVATE-2 studies enrolled patients with HIV-1 RNA >5,000 copies/ mL in spite of ≥6 months of prior therapy with ≥1 agent from 3 of the 4 antiretroviral drug classes or documented resistance or intolerance to ≥1 member of each class. All patients were treated with an optimized background regimen of 3 to 6 antiretroviral agents (excluding low-dose ritonavir) based on the patient's treatment history and baseline genotypic and phenotypic viral resistance measurements. Patients were randomized 2:2:1 to maraviroc 300 mg QD, maraviroc 300 mg BID, or placebo. Doses were adjusted based on background therapy. After 24 weeks of therapy, 60.8% of patients treated with maraviroc 300 mg BID had HIV-1 RNA <400 copies/mL versus 27.8% of patients who received placebo. From baseline to Week 24, patients treated with maraviroc 300 mg BID experienced a mean change in HIV-1 RNA of –1.96 log10. In Study A4001029, patients were required to meet inclusion/exclusion criteria similar to those of MOTIVATE-1 and MOTIVATE-2. Patients were randomized 1:1:1 to maraviroc QD, maraviroc BID, or placebo. Patients treated with maraviroc demonstrated no increased risk of infection or HIV disease progression. Maraviroc use among these patients was not associated with a significant decrease in HIV-1 RNA versus placebo-treated patients.
Safety. Treatment with maraviroc has been associated with hepatotoxicity and an increase in hepatic adverse events. Maraviroc should be used with caution in patients at increased risk for cardiovascular events. Caution should also be used when maraviroc is administered to patients with a history of postural hypotension and in patients taking concomitant medications that are known to lower blood pressure. Combination antiretroviral therapy has been associated with immune reconstitution syndrome. Patients treated with maraviroc may be at increased risk of developing infections. Maraviroc therapy could affect immune surveillance and lead to an increased risk of malignancy. The most common adverse events reported in patients treated with maraviroc include upper respiratory tract infections, cough, pyrexia, rash, musculoskeletal symptoms, abdominal pain, and dizziness.
Pricing. The wholesale acquisition cost of maraviroc is expected to be approximately $29 per day, or $10,585 per year.