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: Richard T Davey, Peter E Pertel, Alice Benson, Delanie J Cassell, Brian G Gazzard, Mark Holodniy, Jacob P Lalezari, Yves Levy, Ronald T Mitsuyasu, Frank J Palella, Richard B Pollard, Prabhu Rajagopalan, Michael S Saag, Robert A Salata, Beverly E Sha, Shurjeel Choudhri
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 28 Issue 2 Pg. 89-100 (Feb 2008) ISSN: 1079-9907 [Print] United States
• PMID: 18279104 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anti-HIV Agents
• Cytokines
• Interleukin-2
• Recombinant Proteins
• aldesleukin

Topics

• Adult
• Anti-HIV Agents (administration & dosage, adverse effects, pharmacokinetics)
• Antiretroviral Therapy, Highly Active
• Cytokines (metabolism)
• Double-Blind Method
• Female
• HIV Infections (drug therapy, immunology, metabolism)
• Humans
• Injections, Subcutaneous
• Interleukin-2 (administration & dosage, adverse effects, agonists, analogs & derivatives, pharmacokinetics)
• Lymphocyte Count
• Male
• Maximum Tolerated Dose
• Middle Aged
• Recombinant Proteins (administration & dosage, adverse effects, pharmacokinetics)