Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults

Jeffrey M. Jacobson, Israel Lowy, Courtney V. Fletcher, Tobias J. Neill, Diep N.H. Tran, Thomas J. Ketas, Alexandra Trkola, Mary E. Klotman, Paul J. Maddon, William C. Olson, Robert J. Israel

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv portions of both the heavy and light chains of human IgG2 have been replaced with the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins, tetravalent PRO 542 potently neutralizes diverse primary human immunodeficiency virus (HIV) type 1 isolates. In this phase 1 study, the first evaluation of this compound in humans, HIV-infected adults were treated with a single intravenous infusion of PRO 542 at doses of 0.2-10 mg/kg. PRO 542 was well tolerated, and no dose-limiting toxicities were identified. Area under the concentration-time curve, and peak serum concentrations increased linearly with dose, and a terminal serum half-life of 3-4 days was observed. No patient developed antibodies to PRO 542. Preliminary evidence of antiviral activity was observed as reductions in both plasma HIV RNA and plasma viremia. Sustained antiviral effects may be achieved with repeat dosing with PRO 542.

Original languageEnglish (US)
Pages (from-to)326-329
Number of pages4
JournalJournal of Infectious Diseases
Volume182
Issue number1
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Jacobson, J. M., Lowy, I., Fletcher, C. V., Neill, T. J., Tran, D. N. H., Ketas, T. J., Trkola, A., Klotman, M. E., Maddon, P. J., Olson, W. C., & Israel, R. J. (2000). Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. Journal of Infectious Diseases, 182(1), 326-329. https://doi.org/10.1086/315698