title: Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy.
abstract: 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.
authors.affiliation: National Institutes of Health, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA. rdavey@niaid.nih.gov
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Peter E
authors.initials: PE
authors.lastname: Pertel
authors.forename: Alice
authors.initials: A
authors.lastname: Benson
authors.forename: Delanie J
authors.initials: DJ
authors.lastname: Cassell
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gazzard
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Mitsuyasu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Prabhu
authors.initials: P
authors.lastname: Rajagopalan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.forename: Beverly E
authors.initials: BE
authors.lastname: Sha
authors.forename: Shurjeel
authors.initials: S
authors.lastname: Choudhri
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin