Brand Name



CD4 (domain 2)-directed post-attachment HIV-1 entry inhibitor

FDA Indication

Combination treatment of multidrug resistant HIV-1 infection†,$


Ibalizumab is the first-in-class CD4 (domain 2)-directed post-attachment HIV-1 entry inhibitor. It was designated as a breakthrough therapy by FDA and approved for combination therapy of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab is a humanized monoclonal IgG4 antibody produced by recombinant DNA technology in murine myeloma nonsecreting 0 cells. It represents the first monoclonal antibody for the treatment of HIV and also the first biologic from China to be marketed in the U.S.90,91

The process of HIV-1 infection begins with entry of the virus into target cells.92 The process is initiated when the surface subunit of the HIV-1 envelope glycoprotein (gp120) binds to a host cell CD4 receptor. Binding to CD4 normally allows access of the virus to the CCR5/CXCR co-receptors necessary for fusion of the virus to the outside of the host cell. By binding the CD4 receptor in a location that does not inhibit gp120 binding by the virus, ibalizumab creates a barrier that prevents the virus from reaching the CCR5/CXCR receptor complex. More specifically, the binding of ibalizumab to domain 1 of the CD4 receptor (and leaving domain 2 unencumbered) prevents the virus from fusing with the host cell while also preserving the ability of virus-bound CD4 cells to perform normal CD4 cell-mediated immune system functions.92,93

Ibalizumab is administered intravenously, preferably via the cephalic vein in the arm, as a single loading dose of 2 g followed by a maintenance dose of 800 mg every 2 weeks.7 The half-life is ~3 days.7 Among a total of 292 patients with HIV-1 infection and premarket exposure to the drug, the most common adverse reactions were diarrhea, dizziness, nausea, and rash.7 One patient developed immune reconstitution inflammatory syndrome manifested as an exacerbation of progressive multifocal leukoencephalopathy. Resistance to ibalizumab associated with virologic failure has been characterized and may be associated with mutations giving rise to changes in the V5 loop of viral gp120 envelope proteins.90

In a premarket study of 40 heavily treatment-experienced subjects with multidrug-resistant HIV-1 and viral loads >1000 HIV-1 RNA copies/mL treated for 24 weeks with ibalizumab, 43% achieved a reduction in viral load to <50 copies/mL.7 Of the 27 study participants who continued in a follow-up study, 59% had <50 copies/mL at week 48 and all 15 subjects who achieved <50 copies by week 24 sustained this level of suppression throughout 48 weeks of therapy.94 U.S. Department of Health and Human Services ART Guidelines issued on October 25, 2018 include the use of ibalizumab for patients who lack the option of a fully suppressive HIV treatment regimen.95 The annual cost of therapy is expected to be $118,000.92,96

Further Reading in Goodman & Gilman’s