title: Administration of imiquimod, an interferon inducer, in asymptomatic human immunodeficiency virus-infected persons to determine safety and biologic response modification.
abstract: A phase I study to determine safety, maximum tolerated dose, and biologic response during multiple once-a-week administration of oral imiquimod, an immune response modifier, was conducted in 12 adults with early human immunodeficiency virus (HIV) infection. All completed the dose-escalation phase of weekly dosing at 100-mg increments and received at least one maintenance dose, 100 mg below the patient's toxic dose, for 12 weeks. Dose-limiting toxicity occurred in 3 patients at 200-mg, 5 at 300-mg, and 3 at 400-mg dose levels. One tolerated the 500-mg dose without dose-limiting toxicity. Dose-limiting toxicities included fatigue, fever, malaise, increased transaminases, hypotension, vomiting, and depression. Seven of 12 completed 12 weeks of maintenance. At > or = 200 mg of imiquimod, all patients had biologic responses, measured by elevations in serum interferon, beta2-microglobulin, and neopterin levels. Imiquimod induced pronounced levels of circulating interferon in asymptomatic HIV-infected persons, with variable effect on virus load.
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. d.goldstein@unsw.edu.au
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: P
authors.initials: P
authors.lastname: Hertzog
authors.forename: E
authors.initials: E
authors.lastname: Tomkinson
authors.forename: D
authors.initials: D
authors.lastname: Couldwell
authors.forename: S
authors.initials: S
authors.lastname: McCarville
authors.forename: S
authors.initials: S
authors.lastname: Parrish
authors.forename: P
authors.initials: P
authors.lastname: Cunningham
authors.forename: M
authors.initials: M
authors.lastname: Newell
authors.forename: M
authors.initials: M
authors.lastname: Owens
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D007369:Interferon Inducers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007372:Interferons / Q000097:blood; D008297:Male; D008875:Middle Aged; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D000634:Aminoquinolines; D007369:Interferon Inducers; D001613:beta 2-Microglobulin; D007372:Interferons; D000077271:Imiquimod