title: A randomized, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus.
abstract: Intermittent administration of interleukin (IL)-2 produces significant and sustained increases in CD4(+) T lymphocyte count in human immunodeficiency virus (HIV)-infected subjects but can be associated with dose-limiting toxicities. The primary objective of this study was to determine whether concomitant administration of prednisone could decrease these toxicities. HIV-seropositive adults receiving highly active antiretroviral therapy (HAART) were randomized to receive either (1) intermittent subcutaneous IL-2 and placebo, (2) intermittent subcutaneous IL-2 and prednisone, (3) intermittent prednisone, or (4) intermittent placebo. Prednisone decreased levels of proinflammatory cytokines during IL-2 cycles but, despite induction of expression of CD25, blunted increases in IL-2-associated CD4(+) T lymphocyte count. Whereas intermittent administration of IL-2 reduced basal proliferation of CD4(+) T cells, this effect was inhibited by prednisone, suggesting that prednisone potentially interferes with IL-2's long-term effects on survival of T lymphocytes.
authors.affiliation: Office of the Clinical Director, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, US. jtavel@nih.gov.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Tavel
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Robert E
authors.initials: RE
authors.lastname: Walker
authors.forename: Barbara
authors.initials: B
authors.lastname: Hahn
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Shyla
authors.initials: S
authors.lastname: Jagannatha
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Judith
authors.initials: J
authors.lastname: Falloon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Julia A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: Randy
authors.initials: R
authors.lastname: Stevens
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.forename: Michael
authors.initials: M
authors.lastname: Baseler
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011241:Prednisone / Q000008:administration & dosage* / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D005938:Glucocorticoids; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011241:Prednisone