Phase I Trial of Interferon Alfa-n3 in Early-Stage Human Immunodeficiency Virus Type 1 Disease: Evidence for Drug Safety, Tolerance, and Antiviral Activity

• Published in: The Journal of infectious diseases 1996-05, Vol.173 (5), p.1107-1114
• Main Authors: Skillman, Donald R., Malone, Joseph L., Decker, Catherine F., Wagner, Kenneth F., Mapou, Robert L., Liao, Mei-June, Testa, Douglas, Meltzer, Monte S.
• Format: Article
• Language: English
• Subjects: Adult; AIDS; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - analysis; Antiviral Agents - therapeutic use; Antivirals; Biological and medical sciences; CD4 Lymphocyte Count; Dosage; Erythrocytes - immunology; Female; GTP-Binding Proteins; Histocompatibility Antigens Class I - analysis; HIV 1; HIV Infections - therapy; human immunodeficiency virus 1; Humans; Infections; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Interferons; Kaposi sarcoma; Leukocytes - immunology; Major Articles; Male; Medical sciences; Middle Aged; Myxovirus Resistance Proteins; Neuropsychological Tests; Pharmacology. Drug treatments; Proteins - analysis; RNA; RNA, Viral - blood; Viruses; White people
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/173.5.1107

The safety and tolerance of interferon alfa-n3 (IFN-αn3) was tested in 20 adults with asymptomatic human immunodeficiency virus type 1 (HIV-l) infection (>400 CD4Iymphocytes/mm3). IFN-αn3 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. IFNαn3 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-αn3 induced IFN-specific biologic responses and dose-related antiviral activity against HIV-1. Subjects showed stabilization of CD4 cells for > 20 months. IFN-αn3 should be studied in combination with other antiretroviral agents and in persons with more advanced HIV-1 infection.