Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy.
We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary.
Davey
Richard T
RT
National Institutes of Health, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA. rdavey@niaid.nih.gov
Pertel
Peter E
PE
Benson
Alice
A
Cassell
Delanie J
DJ
Gazzard
Brian G
BG
Holodniy
Mark
M
Lalezari
Jacob P
JP
Levy
Yves
Y
Mitsuyasu
Ronald T
RT
Palella
Frank J
FJ
Pollard
Richard B
RB
Rajagopalan
Prabhu
P
Saag
Michael S
MS
Salata
Robert A
RA
Sha
Beverly E
BE
Choudhri
Shurjeel
S
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000819:agonists / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018655:Lymphocyte Count; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin