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Journal article
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
Antimicrobial agents and chemotherapy, v 53(2), pp 450-457
Feb 2009
PMID: 19015347
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 log(10)) 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.
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Details
- Title
- 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
- Creators
- Jeffrey M Jacobson - Drexel UniversityDaniel R Kuritzkes - Brigham and Women's HospitalEliot Godofsky - Bach & Godofsky Infectious DiseasesEdwin DeJesus - IDC Research Initiative, Altamonte Springs, FloridaJeffrey A Larson - Tanox, Incorporated, Houston, TexasSteven P Weinheimer - TaiMed Biologics, Inc., Bellaire, TexasStanley T Lewis - The University of Texas Health Science Center at Houston
- Publication Details
- Antimicrobial agents and chemotherapy, v 53(2), pp 450-457
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000262646500012
- Scopus ID
- 2-s2.0-59749089619
- Other Identifier
- 991019335234704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy