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Abstract
SAFETY AND ACTIVITY OF RECOMBINANT HUMAN INTERLEUKIN-12 (RHIL-12) IN HIV+ PATIENTS
POLLARD R, JACOBSON M, LANDAY A, SPRITZLER J, FOX L, SCHOCK B, CHAN E
Objective/Background: To evaluate the safety and activity of rhIL-12, a cytokine that stimulates T and NK cells to generate a TH1 type immune response. Exogenously administered rhIL-12 might maintain TH1 cellular immune responses and thus be beneficial to long-term survivors of HIV infection.
Methods: In a randomized, placebo-controlled trial, HIV+ patients on antiretroviral therapy received rhIL-12 or placebo biweekly for 4 wks. Patients with CD4 counts <50 were assigned, 3:1, rhIL-12 (30, 100 or 300 ng/kg) or placebo in dose-escalated cohorts. Patients with CD4 counts=300-500 were assigned, 1:1:1, rhIL-12 100 ng/kg, rhIL-12 300 ng/kg or placebo. Subjects were monitored for safety; changes in absolute lymphocyte subset, serum IFN?, serum neopterin, and plasma HIV RNA levels; lymphocyte proliferative responses to PHA, tetanus, candida, MAC, and HIV p24 and gp120 antigens; and PBMC inducible IFN? responses to PHA.
Final Results: rhIL-12 was well tolerated at doses up to 100 ng/kg in patients enrolled with CD4 counts <50 and at all doses in patients with CD4 counts =300-500. At baseline, immune responses were directly proportional to baseline CD4 count. rhIL-12 administration resulted in highly significant, dose-related, increases in serum neopterin, a marginally significant increase in serum IFN? at the 300 ng/kg dose only, but no significant changes in HIV RNA, lymphocyte subsets, or lymphocyte proliferative or inducible IFN? responses to specific antigens.
Conclusion: rhIL-12 administered biweekly at doses up to 300 ng/kg was well tolerated in HIV+ patients with CD4 counts in the 300-500 range and resulted in significant, dose-related, increases in serum neopterin (probably reflecting the effect of systemic IFN? induction). However, there was no evidence of augmentation of antigen-specific immune response. The effects of rhIL-12 may have relevance for the treatment of AIDS-related OI’s or for strategies designed to activate the latent HIV reservoir.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
106
Suggested Citation
"POLLARDR, et al.
SAFETY AND ACTIVITY OF RECOMBINANT HUMAN INTERLEUKIN-12 (RHIL-12) IN HIV+ PATIENTS.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
106"
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