4th Conference on Retroviruses and Opportunistic Infections Washington, DC - January 22-26, 1997

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:71 (abstract no. 36)

Walker RE, Hahn B, Kelly GG, Miller K, Piscitelli S, Figg WD, Davey RT, Falloon J, Kovacs JA, Polis MA, Masur H, Metcalf JA, Baseler M, Fyfe G, Thomas S, McCloskey RV, Lane HC; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Background: Continuous 5 day IV infusions of IL-2 given every 8 weeks for 1 year produce greater than or equal to 50% increases in CD4 counts in a majority of HIV-1 infected patients with baseline CD4 greater than 200. In pilot studies, dose-limiting constitutional symptoms and transient increases in viral load paralleled increases in serum levels of TNF-alpha. Anti-TNF antibodies and thalidomide inhibit TNF in vitro and in vivo.

Objective: To determine if TNF inhibition during IL-2 treatment would reduce IL-2 associated adverse events and ablate viral activation.

Methods: Patients with CD4=200-500 were randomized to receive IL-2 alone, IL-2 plus chimeric murine-human anti-TNF monoclonal antibody (cA2) (1 mg/kg on days 1 and 4 of IL-2), or IL-2 plus thalidomide (100 mg PO q8h). IL-2 was administered by continuous 5 day IV infusions q8wk.

Results: 13 patients to date received greater than or equal to 6 months of therapy: 3 with IL-2 alone; 5 with IL-2 plus anti-TNF; 5 with IL-2 plus thalidomide. CD4 count increases over 6 months were not substantially different among the groups. Mean(median) CD4 at baseline=304(249) for IL-2 alone; 401(383) for IL-2 plus anti-TNF; and 384(353) for IL-2 plus thalidomide. At month 6, counts were 397(369), 452(454), and 538(631), respectively. Mean number of moderate to severe adverse events/patient-cycle were 1.2, 0.8, and 1.4, respectively. Transient viral load increases during the IL-2 infusions were observed in all 3 groups. Over 6 months, median viral load changes by bDNA (log₁₀) were -0.19, -0.05, and -0.05, respectively. Peak serum TNF levels (pg/ml) by ELISA during the first IL-2 cycle ranged from 9-15, 175-433, and 6-20, respectively, for the 3 groups.

Conclusions: At the doses studied, IL-2 administered with anti-TNF antibody (cA2) or thalidomide was safe. Further evaluation at higher doses of thalidomide and cA2 on TNF blockade will be necessary to assess the contribution of TNF to IL-2 treatment toxicity.

970122
36

Copyright © 1980, 1997 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed through AIDSLINE, National Library of Medicine.