A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3.
A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ¿MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.
Losso
M H
MH
Servicio de Inmunocomprometidos, Dept. of Medicine, Hospital JM Ramos Mejia, 1221 Buenos Aires, Argentina. hivramos@elsitio.net.
Belloso
W H
WH
Emery
S
S
Benetucci
J A
JA
Cahn
P E
PE
Lasala
M C
MC
Lopardo
G
G
Salomon
H
H
Saracco
M
M
Nelson
E
E
Law
M G
MG
Davey
R T
RT
Allende
M C
MC
Lane
H C
HC
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016049:Didanosine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage; D019829:Nevirapine / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage; D019258:Saquinavir / Q000008:administration & dosage; D018119:Stavudine / Q000627:therapeutic use; D016047:Zalcitabine / Q000008:administration & dosage; D015215:Zidovudine / Q000008:administration & dosage
D019380:Anti-HIV Agents; D007376:Interleukin-2; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D016047:Zalcitabine; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir