Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.

Objectives: 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).

Design: Open-label, dose-escalation.

Setting: Multiple center study.

Subjects: Twenty HIV-infected children, aged 3-12 years.

Intervention: 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.

Main Outcome Measures: 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.