title: Phase I trial of interferon alfa-n3 in early-stage human immunodeficiency virus type 1 disease: evidence for drug safety, tolerance, and antiviral activity.
abstract: The safety and tolerance of interferon alfa-n3 (IFN-alpha n3) was tested in 20 adults with asymptomatic human immunodeficiency virus type 1 (HIV-1) infection (> 400 CD4 lymphocytes/mm3). IFN-alpha n3 was self-injected three times per week for 3-6 months: 5 patients received 1 mega-IU (MIU)/dose, 10 received 5 MIU/dose, and 5 escalated to their maximum tolerated dose. Subjects were evaluated every 2-4 weeks through 2 months after cessation of treatment. Neuropsychological tests were given at 3-month intervals. Markers of IFN activity, anti-IFN neutralizing antibodies, and antiviral response were measured monthly. IFN-alpha n3 was safe and well tolerated: influenza-like symptoms were uncommon, laboratory toxicity was minimal, no adverse neurobehavioral side effects were evident, and no patient developed neutralizing antibodies against IFN. IFN-alpha n3 induced IFN-specific biologic responses and dose-related antiviral activity against HIV-1. Subjects showed stabilization of CD4 cells for > 20 months. IFN-alpha n3 should be studied in combination with other antiretroviral agents and in persons with more advanced HIV-1 infection.
authors.affiliation: Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Skillman
authors.forename: J L
authors.initials: JL
authors.lastname: Malone
authors.forename: C F
authors.initials: CF
authors.lastname: Decker
authors.forename: K F
authors.initials: KF
authors.lastname: Wagner
authors.forename: R L
authors.initials: RL
authors.lastname: Mapou
authors.forename: M J
authors.initials: MJ
authors.lastname: Liao
authors.forename: D
authors.initials: D
authors.lastname: Testa
authors.forename: M S
authors.initials: MS
authors.lastname: Meltzer
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D009483:Neuropsychological Tests; D011506:Proteins / Q000032:analysis; D012367:RNA, Viral / Q000097:blood
chemical_list: D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D012367:RNA, Viral; D019204:GTP-Binding Proteins