Phase I trial of interferon alfa-n3 in early-stage human immunodeficiency virus type 1 disease: evidence for drug safety, tolerance, and antiviral activity

J Infect Dis. 1996 May;173(5):1107-14. doi: 10.1093/infdis/173.5.1107.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / analysis
  • Antiviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Erythrocytes / immunology
  • Female
  • GTP-Binding Proteins*
  • HIV Infections / therapy*
  • HIV-1*
  • Histocompatibility Antigens Class I / analysis
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Leukocytes / immunology
  • Male
  • Middle Aged
  • Myxovirus Resistance Proteins
  • Neuropsychological Tests
  • Proteins / analysis
  • RNA, Viral / blood

Substances

  • Antiviral Agents
  • Histocompatibility Antigens Class I
  • Interferon-alpha
  • Myxovirus Resistance Proteins
  • Proteins
  • RNA, Viral
  • GTP-Binding Proteins