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Antimicrobial Agents and Chemotherapy, February 2009, p. 450-457, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00942-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Safety, Pharmacokinetics, and Antiretroviral Activity of Multiple Doses of Ibalizumab (formerly TNX-355), an Anti-CD4 Monoclonal Antibody, in Human Immunodeficiency Virus Type 1-Infected Adults {triangledown}

Jeffrey M. Jacobson,1* Daniel R. Kuritzkes,2 Eliot Godofsky,3 Edwin DeJesus,4 Jeffrey A. Larson,5 Steven P. Weinheimer,6 and Stanley T. Lewis6,7

Drexel University College of Medicine, Philadelphia, Pennsylvania,1 Brigham and Women's Hospital and Harvard University School of Medicine, Boston, Massachusetts,2 Bach and Godofsky, Bradenton, Florida,3 IDC Research Initiative, Altamonte Springs, Florida,4 Tanox, Incorporated, Houston, Texas,5 TaiMed Biologics, Inc., Bellaire, Texas,6 University of Texas Medical School—Houston, Houston, Texas7

Received 16 July 2008/ Returned for modification 24 August 2008/ Accepted 7 November 2008

Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log10) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4+ T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4+ T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.

* Corresponding author. Mailing address: Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, 245 N. 15th Street, MS 461, Philadelphia, PA 19102. Phone: (215) 762-6555. Fax: (215) 762-3031. E-mail: jeffrey.jacobson{at}drexelmed.edu

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 450-457, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00942-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vermeire, K., Van Laethem, K., Janssens, W., Bell, T. W., Schols, D. (2009). Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol. 83: 9577-9583 [Abstract] [Full Text]  


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