A phase I study of the pharmacokinetics and safety of passive immunotherapy with caprine anti-HIV antibodies, PEHRG214, in HIV-1-infected individuals

Abstract

Purpose: To establish the pharmacokinetics and safety of single-dose polyclonal caprine anti-HIV antibodies (PEHRG214) 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 ≤200 cells/μL and plasma HIV viral load (VL) of ≥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/μL and 126,200 copies/mL, respectively. HRG exhibited linear pharmacokinetics across the dosing range studied. The mean terminal elimination half-life (t1/2) 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 log10 copies/mL (n = 1), or declined by 0.34-1.55 log10 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. © 2004 Thomas Land Publishers, Inc.