Ibalizumab-uiyk is an injectable recombinant monoclonal antibody that binds to the surface proteins of CD4 cells leading to conformational changes that prevent the postattachment steps required for HIV-1 fusion and entry into the cell. It is the only monoclonal medication used in the treatment of HIV. Because of its unique binding specificity, ibalizumab-uiyk blocks viral entry without causing immunosuppression, a concern in many monoclonal medications.[4,15] It is indicated in combination with other ARVs for treatment in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 who are failing their current ARV therapy regimen.
The approval of ibalizumab-uiyk was based on a trial conducted on 40 HTE HIV patients with viral load greater than 1,000 copies/mL and a documented resistance to at least one NRTI, NNRTI, and a protease inhibitor. Patients were also required to have had at least 6 months of treatment and to have recently failed therapy. The trial included three periods, beginning with a 6-day period where baseline viral load was established and confirmed (control period). On day 7, patients received a 2,000-mg loading dose of ibalizumab-uiyk in addition to their standard ART regimen (functional monotherapy period). At day 14, viral load was reassessed and regimens were monitored and adjusted to ensure proper activity against their HIV infection. Ibalizumab-uiyk 800 mg was administered IV every 2 weeks until conclusion of the study (maintenance period). The primary endpoint evaluated the difference in the proportion of viral load decrease from the control period to the functional monotherapy period, specifically comparing the percentage of patients with a ≥0.5 log10 decrease in overall viral load. During the control period, 3% of patients were found to have such a decrease, while the functional monotherapy period resulted in 83% of patients meeting the stated viral-load decrease. At the end of 25 weeks, 43% of patients achieved a viral load of <50 copies/mL.
Based on this study, the approved dosing of ibalizumab-uiyk is a one-time IV loading dose of 2,000 mg, followed by an 800-mg IV maintenance dose every 2 weeks.[4,16] Careful monitoring is required for 1 hour after administration of the first infusion for infusion-related reactions, with subsequent infusion monitoring reduced to 15 minutes after toleration of the initial dose. Ibalizumab-uiyk seems to be otherwise well-tolerated; the most adverse effects associated with ibalizumab-uiyk were nausea, dizziness, and diarrhea.[4,16]
US Pharmacist. 2020;45(10):17-25. © 2020 Jobson Publishing