Subcutaneous interleukin-2 in combination with anti-retroviral therapy for treatment of HIV-1-infected subjects.
A total of 11 HIV-1 positive patients, with CD4+ cell counts between 200 and 500/microl, who were in stable anti-retroviral therapy, were treated with subcutaneous recombinant human IL-2 thrice weekly administered on an out-patient basis in a dose-escalating manner. Subcutaneous IL-2 was well tolerated and associated with only mild to moderate constitutional symptoms and local inflammation at the injection site. CD4+ cell count increased from 404 +/- 48/microl at baseline to 639 +/- 88/microl at week 6, with proportionate increases in naive cells and memory cells. Increased doses of IL-2 were then needed to sustain the number of CD4+ cells. After discontinuation of IL-2 treatment, CD4+ cell count returned to baseline levels. IL-2 induced a reduction in the percentage of CD8+ CD38+ and CD8+ HLA-DR+ cells, an increase in the fraction of CD8+ CD25+ and CD8+ CD122+, and an elevation in the number of NK-cells. IL-2 did not induce any clinically significant change in plasma HIV-RNA. In conclusion, IL-2 can safely be administered subcutaneously on an out-patient basis to HIV-infected individuals with CD4+ cell counts from 200/microl to 500/microl and with some improvement in immunological abnormalities. Continuous therapy, however, seems to result in the development of tachyphylaxia.
Larsen
C S
CS
Department of Medicine and Infectious Diseases, Aarhus University Hospital, Denmark.
Ostergård
L
L
Møller
B K
BK
Buhl
M R
MR
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016827:CD8 Antigens / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000097:blood / Q000627:therapeutic use*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000032:analysis; D012367:RNA, Viral / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013618:Tachyphylaxis; D013997:Time Factors
D019380:Anti-HIV Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1