Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.
OBJECTIVE
To define the tolerated dose of recombinant interleukin-2 (rIL-2) in HIV-infected children (part A), and to determine the safety and immunologic effects of the tolerated rIL-2 dose in a cohort of HIV-infected children (part B).


METHODS
Open-label, dose-escalation.


METHODS
Multiple center study.


METHODS
Twenty HIV-infected children, aged 3-12 years.


METHODS
In part A six subjects received 1 x 10(6) IU/m2 and four subjects received 4 x 10(6) IU/m2 rIL-2 by continuous intravenous infusion for 5 days every 8 weeks for three cycles. In part B 10 different subjects received 1 x 10(6) IU/m2 for 5 days every 8 weeks for six cycles.


METHODS
Toxicity, CD4 cell count and percentage, and viral load.


RESULTS
The tolerated dose of rIL-2 was 1 x 10(6) IU/m2. The most common side effects were fever and vomiting. Of 10 subjects enrolled in part B of the study, five discontinued rIL-2 therapy for a variety of reasons, most related to administration of study drug. Comparable rises in CD4 cell count and percentage were observed in each of the treatment arms. Six cycles of rIL-2 therapy did not appear to be better than three cycles with respect to improvement of CD4 parameters. Transient rises in plasma HIV-1 RNA levels were detected in some subjects.


CONCLUSIONS
These results suggest that rIL-2 therapy can raise CD4 cell counts and percentages in some HIV-infected children, although a high proportion of HIV-infected children may have to discontinue intravenous therapy because of drug- or administration-related toxicity. Controlled trials of rIL-2 in this patient population are warranted.
Starr
Stuart E
SE
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, USA.
McFarland
Elizabeth J
EJ
Muresan
Petronella
P
Fenton
Terence
T
Pitt
Jane
J
Douglas
Steven D
SD
Deveikis
Audra
A
Levin
Myron J
MJ
Rathore
Mobeen H
MH
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D019380:Anti-HIV Agents; D007376:Interleukin-2; D012367:RNA, Viral