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

PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein th e Fv portions of both the heavy and light chains of human IgG2 have been re placed with the D1D2 domains of human CD4. Unlike monovalent and divalent C D4-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 ident ified. Area under the concentration-time curve, and peak serum concentratio ns increased linearly with dose, and a terminal serum half-life of 3-4 days was observed. No patient developed antibodies to PRO 542. Preliminary evid ence of antiviral activity was observed as reductions in both plasma HIV RN A and plasma viremia. Sustained antiviral effects may be achieved with repe at dosing with PRO 542.