Publications & Reports

A phase I study of the pharmacokinetics and safety of passive immunotherapy with caprine anti-HIV antibodies, (PE)HRG214, in HIV-1-infected individuals.

Pett SL, Williams LA, Day RO, Lloyd AR, Carr AD, Clezy KR, Emery S, Kaplan E, McPhee DA, McLachlan AJ, Gelder FB, Lewin SR, Liauw W, Williams KM
HIV, Immunology and Infectious Diseases Clinical Services, St. Vincent's Hospital, Sydney, and National Centre in HIV Epidemiology and Clinical Research, University of NSW, Darlinghurst, Sydney, Australia. spett@nchecr.unsw.edu.au

Abstract

PURPOSE: To establish the pharmacokinetics and safety of single-dose polyclonal caprine anti-HIV antibodies ((PE)HRG214)in HIV-1-infected individuals.

DESIGN: A phase 1, open-label, nonrandomized, dose-escalating study.

METHOD: HIV-1-infected patients with CD4+ T-cell counts of < or =200 cells/microL and plasma HIV viral load (VL)of > or =5,000 copies/mL received a single intravenous dose of HRG. Dosing began at 6,000 U/kg HRG with proposed step-wise escalation to 96,000 U/kg.

RESULTS: Eleven males were enrolled; median CD4+T-cell count and VL were 96 cells/microL and 126,200 copies/mL, respectively. HRG exhibited linear pharmacokinetics across the dosing range studied. The mean terminal elimination half-life (t(½)) was 136.6 +/- 44.6 hours (range, 52.6-198 h). Serum sickness occurred in one 48,000 U/kg HRG recipient. One 6,000 U/kg and two 24,000 U/kg HRG recipients developed a mild rash. Between baseline and day 60, VL remained unchanged (n = 6), increased by 0.67 log(10) copies/mL (n = 1), or declined by 0.34-1.55 log(10) copies/mL (n = 4).

CONCLUSION: Single-dose HRG exhibited linear kinetics and a long half-life. Although numbers in each dosing group were very small (n = 3), HRG was generally well tolerated in doses below 48,000 U/kg. Multiple dosing with HRG in the HIV-salvage setting may be complicated by immune-complex formation.

Publication

  • Journal: HIV Clinical Trials
  • Published: 01/03/2004
  • Volume: 5
  • Issue: 2
  • Pagination: 91-98

Health Issue