- ADJUNCT ASSISTANT CLINICAL PROFESSOR Medicine, Infectious Diseases
molecular biology and application of human T-cell immortalization with Herpesvirus saimiri
Jacobson J, Lowy I, Fletcher CV, O'Neill TJ, Tran DN, Ketas TJ, Trkola A, Klotman M, Maddon PJ, Olson WC, Israel RJ. Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. J Infect Dis 2000 Jul; 182(1): 326-9.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.
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Dr.Lowy is not currently required to report Industry relationships.
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