A phase I study of interferon-alpha 2b in combination with interleukin-2 in patients with human immunodeficiency virus infection.
Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4+ T cells/mm3. A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4+ T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 x 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity.
Schnittman
S M
SM
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Vogel
S
S
Baseler
M
M
Lane
H C
HC
Davey
R T
RT
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000628:therapy
D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins