A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine.
OBJECTIVE
A Phase I study of subcutaneous recombinant interleukin-2 (rIL-2).


METHODS
Sixteen patients with advanced HIV infection receiving 600-1200 mg zidovudine per day were divided into three groups, which received sequentially 0.2 x 10(6), 0.7 x 10(6) or 2 x 10(6) units/m2 per day of rIL-2 subcutaneously 5 consecutive days.


METHODS
Five-day admission to an academic tertiary care hospital.


METHODS
Sixteen unblinded, non-randomized volunteers.


METHODS
Subcutaneous rIL-2.


METHODS
Tolerance, toxicity, hematologic, immunologic and antiviral responses.


RESULTS
rIL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rIL-2 administration, with rebound within 48 h after rIL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rIL-2 receptor levels increased transiently during and immediately following rIL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rIL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden.


CONCLUSIONS
Subcutaneous rIL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261.
D K
DK
McMahon
J A
JA
Armstrong
X L
XL
Huang
C R
CR
Rinaldo
P
P
Gupta
T L
TL
Whiteside
G J
GJ
Pazin
C
C
Tripoli
M
M
Ho
D000328:Adult; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015215:Zidovudine