|Title||Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, Weinheimer S, Marsolais C, Lewis S|
|Journal||N Engl J Med|
|Date Published||2018 08 16|
|Keywords||Adult, Aged, Anti-HIV Agents, Antibodies, Monoclonal, CD4 Lymphocyte Count, Diarrhea, Drug Resistance, Multiple, Viral, Drug Therapy, Combination, Female, HIV Fusion Inhibitors, HIV Infections, HIV-1, Humans, Injections, Intravenous, Male, Middle Aged, Viral Load, Young Adult|
BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4.
METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later. Through week 25 of the study, patients received 800 mg of ibalizumab every 14 days, combined with an individually optimized background regimen including at least one fully active agent. The primary end point was the proportion of patients with a decrease in viral load of at least 0.5 log copies per milliliter from baseline (day 7) to day 14.
RESULTS: A total of 31 patients completed the study. The mean baseline viral load was 4.5 log copies per milliliter, and the mean CD4 count was 150 per microliter. Of the 40 patients in the intention-to-treat population, 33 (83%) had a decrease in viral load of at least 0.5 log copies per milliliter from baseline (P
CONCLUSIONS: In patients with MDR HIV-1 infection who had advanced disease and limited treatment options, ibalizumab had significant antiviral activity during a 25-week study. Evidence of the emergence of diminished ibalizumab susceptibility was observed in vitro in patients who had virologic failure. (Funded by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed Biologics; TMB-301 ClinicalTrials.gov number, NCT02475629 .).
|Alternate Journal||N. Engl. J. Med.|