A phase I, placebo-controlled trial of multi-dose recombinant human interleukin-12 in patients with HIV infection

Mark A. Jacobson, John Spritzler, Alan Landay, Ellen Chan, David Katzenstein, Barbara Schock, Lawrence Fox, Joana D'Arc Roe, Smriti Kundu, Richard Pollard

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Objectives: Interleukin (IL)-12 is a cytokine that stimulates T lymphocytes and natural killer cells to generate a Type 1 T-helper lymphocyte immune response. The primary objective of this study was to determine the safety and immunologic activity of repeated recombinant human IL-12 (rhlL-12) dosing in HIV-infected patients over a broad range of the HIV disease spectrum. Design: A randomized, placebo-controlled, Phase 1 trial design was chosen to control for the effects of HIV disease alone on safety and immunologic measurements. Methods: HIV-infected patients on antiretroviral therapy received rhlL-12 or placebo twice weekly for 4 weeks. Subjects were monitored for safety and changes in absolute lymphocyte subset number, serum interferon (IFN)γ and neopterin levels, plasma HIV RNA level, peripheral blood mononuclear cell (PBMC)-inducible IFNγ responses to mitogen, and PBMC proliferative responses to phytohemagglutinin, tetanus, Candida, Mycobacterium avium complex, streptokinase, and HIV p24 and gp160 antigens. Results: rhlL-12 was well tolerated at doses up to 100 ng/kg in subjects enrolled with CD4 cell counts < 50 × 106 cells/I and at all doses in subjects with CD4 cell counts of 300 × 106-500 × 106 cells/I. rhlL-12 resulted in dose-related increases in serum neopterin (particularly in subjects with baseline CD4 cell counts of 300-500 × 106 cells/I) but in no significant changes in other immunologic measurements or plasma HIV RNA levels. Conclusions: rhlL-12 dosed twice weekly at ≤ 100 ng/kg was well tolerated in HIV-infected patients and resulted in dose-related increases in serum neopterin (possibly reflecting the effect of some degree of IFNγ induction). However, there was no evidence of improvement in antigen-specific immune response.

Original languageEnglish (US)
Pages (from-to)1147-1154
Number of pages8
Issue number8
StatePublished - May 24 2002
Externally publishedYes


  • AIDS
  • Cytokines
  • HIV
  • Interleukin-12
  • T-helper 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


Dive into the research topics of 'A phase I, placebo-controlled trial of multi-dose recombinant human interleukin-12 in patients with HIV infection'. Together they form a unique fingerprint.

Cite this