Selzentry (maraviroc) is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Blocking this interaction prevents CCR5-tropic HIV-1 entry into cells.
Selzentry is specifically indicated, in combination with other antiretroviral agents, for treatment experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
Selzentry is supplied as a film coated tablet designed for oral administration.
The recommended initial dose of this drug differs based on concomitant medications due to drug interactions. It must be given in combination with other antiretroviral medications.
Selzentry plus CYP3A inhibitors (with or without a
The recommended initial dose of Selzentry is 150 mg twice daily.
Selzentry plus other concomitant medications,
including tipranavir/ritonavir, nevirapine, all NRTIs and
The recommended dose is 300 mg twice daily.
Selzentry plus CYP3A inducers (without a strong
The recommended initial dose of Selzentry is 600 mg twice daily.
FDA approval of Selzentry was based on the results of one completed clinical trial, A4001029, and two ongoing clinical trials, A4001027 (MOTIVATE-1) and A4001028 (MOTIVATE-2).
This exploratory, randomized, double blind, multicenter trial was designed to determine the safety and efficacy of maraviroc in subjects infected with dual/mixed co-receptor tropic HIV-1. Subjects were randomized in a 1:1:1 ratio to Selzentry once daily, Selzentry twice daily, or placebo. Selzentry treatment was not associated with increased risk of infection or HIV disease progression nor was it associated with a significant decrease in HIV-1 RNA compared to placebo. In addition, no adverse effect was noted on CD4 cell count.
A4001027 (MOTIVATE-1) and A4001028
These ongoing, double-blind, randomized, placebo-controlled, multicenter studies enrolled approximately 1,000 subjects infected with CCR5-tropic HIV-1. All subjects received an optimized background therapy (OBT) of consisting of 3 to 6 antiretroviral agents (excluding low-dose ritonavir). They were then randomized 2:2:1 to maraviroc 300 mg once daily, maraviroc 300 mg twice daily, or placebo. Pooled analysis at 24 weeks revealed the percentage of subjects with a mean change from baseline to week 24 in HIV-1 RNA (log10 copies/mL) to <400 copies/mL was 60.8% in the Selzentry group versus 27.8% for placebo. The percentage of subjects with a mean change from baseline to week 24 in HIV-1 RNA (log10 copies/mL) to <50 copies/mL was 45.3% in the Selzentry arm compared to 23.0% in the placebo arm. The mean changes in plasma HIV-1 RNA from baseline to week 24 was -1.96 log10 copies/mL for subjects receiving maraviroc + OBT compared to -0.99 log10 copies/mL for subjects receiving OBT only. The mean increase in CD4+ counts was higher on maraviroc twice daily + OBT (106.3 cells/mm3) than on placebo + OBT (57.4 cells/mm3 ).
Ongoing Study Commitments
Adverse events associated with the use of Selzentry may include, but are not limited to, the following:
Selzentry (maraviroc) is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.
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Fätkenheuer G, Pozniak AL, Johnson MA, Plettenberg A, Staszewski S, Hoepelman AI, Saag MS, Goebel FD, Rockstroh JK, Dezube BJ, Jenkins TM, Medhurst C, Sullivan JF, Ridgway C, Abel S, James IT, Youle M, van der Ryst E Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nature Medicine 2005 Nov;11(11):1170-2. Epub 2005 Oct 5
Wood A, Armour D The discovery of the CCR5 receptor antagonist, UK-427,857, a new agent for the treatment of HIV infection and AIDS. Progress in Medicinal Chemistry 2005;43:239-71
Walker DK, Abel S, Comby P, Muirhead GJ, Nedderman AN, Smith DA Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV. Drug Metabolism and Disposition: The Biological Fate of Chemicals 2005 Apr;33(4):587-95
For additional information regarding Selzentry or HIV, please visit the Selzentry web page.