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


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


METHODS
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(1/2)) 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 log(10) copies/mL (n = 1), or declined by 0.34-1.55 log(10) copies/mL (n = 4).


CONCLUSIONS
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.
Pett
Sarah L
SL
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
Williams
Lisa A
LA
Day
Richard O
RO
Lloyd
Andrew R
AR
Carr
Andrew D
AD
Clezy
Kathleen R
KR
Emery
Sean
S
Kaplan
Errol
E
McPhee
Dale A
DA
McLachlan
Andrew J
AJ
Gelder
Frank B
FB
Lewin
Sharon R
SR
Liauw
Winston
W
Williams
Kenneth M
KM
D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D019540:Area Under Curve; D006041:Goats / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007275:Injections, Intravenous; D008297:Male; D010865:Pilot Projects
D000914:Antibodies, Viral; D007106:Immune Sera; D007074:Immunoglobulin G