11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:29 (abstract no. LB.B.6038)
Smith KA, Jacobson L, Pilaro F; New York Hospital-Cornell University Medical College, New York, NY. Fax: (212) 746-8167. E-mail: kasmith@mail.med.cornell.edu.

OBJECTIVES: When administered in high doses to HIV+ individuals, interleukin 2 (IL-2) causes extreme toxicity and markedly increases plasma HIV levels. Integration of the information from the structure-activity relationships of the IL-2 receptor interaction, the cellular distribution of the different classes of IL-2 receptors, and the pharmacokinetics of IL-2 provides for the rationale that low IL-2 doses should circumvent toxicity.

METHODS: To identify a nontoxic, but effective and safe IL-2 treatment regimen that does not stimulate viral replication, doses of IL-2 from 62,500 to 250,000 IU/m(2)/d were administered subcutaneously for 6 months to 16 HIV+ individuals with 200-500 CD4+ T cells/mm³. IL-2 was already detectable in the plasma of most HIV+ individuals even before therapy. Peak plasma IL-2 levels were near saturating for high affinity IL-2 receptors in ten individuals who received the maximum nontoxic dose, which ranged from 187,500 to 250,000 IU/m(2)/d.

RESULTS AND CONCLUSIONS: During the 6 months of treatment at this dose range, plasma levels of proinflammatory cytokines remained undetectable, and plasma HIV RNA levels did not change significantly. However, delayed-type hypersensitivity responses to common recall antigens were markedly augmented, and there were IL-2-dose-dependent increases in circulating NK cells, eosinophils, and monocytes. CD4+ T cells increased at a rate of 27 cells/mm³/month, so that during 6 months of IL-2 therapy, circulating CD4+ T cells increased from 383 plus or minus 45 cells/mm³ (mean plus or minus SE) to 543 plus or minus 110 cells/mm³. Expanded clinical trials of low dose IL-2 are now warranted, especially in combination with effective antivirals to test for the prevention of the immunodeficiency and the emergence of drug-resistant mutants, and for eradication of residual virions.

960707
LBB6038

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