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Ibalizumab is a CD4-specific antibody used to treat HIV infections.
Ibalizumab is a CD4-specific antibody used to treat HIV infections.
Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors. Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 . Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion . CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function . In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action .
Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen . The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with ≥10 antiretroviral medications .
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