Tavel JA, Walker RE, Hahn B, Kovacs JA, Stevens RA, Davey RT, Falloon J, Polis MA, Masur H, Metcalf JA, Lane HC; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 147 (abstract no. 348).

NIAID, Bethesda, MD.

Background: Recombinant IL-2 (rIL-2) can produce significant and sustained increases in CD4+ cell count but is associated with constitutional symptoms including flu-like symptoms which may be dose-limiting. Prednisone has potent anti-inflammatory properties. The objective of this prospective, randomized, double-blind, placebo-controlled clinical trial was to determine if prednisone given during rIL-2 administration decreased rIL-2-associated toxicities, allowed higher rIL-2 dosing and effected rIL-2-associated immunologic outcomes. Methods: HIV-seropositive adults on highly active antiretroviral therapy with baseline CD4+ cell counts over 350 cells/mm3 were randomized to receive rIL-2 7.5 MIU SQ BID for 5 days every 8 weeks in combination with placebo or prednisone dosed at 0.5 mg/kg divided into two daily doses during and two days after rIL-2 administration. rIL- 2 dose could be adjusted in decrements of 1.5 MIU per dose for toxicity management. Analyses were performed on an intent-to-treat basis. Results: Ten patients completed a total of 37 cycles of rIL-2 with prednisone or placebo with a mean follow-up of 7 months. Mean IL-2 dose per cycle was 58.7 MIU in the placebo group and 61.3 MIU in the prednisone group (p = 0.17). A total of 31 grade 3 or 4 toxicities were observed in 3 patients receiving placebo, compared with 3 grade 3 or 4 toxicities in 2 patients receiving prednisone (p < 0.001). Slope analysis of CD4+ cell count change demonstrated a mean increase of 0.7 cells per day in the prednisone group and 2.4 cells per day in the placebo group (p = 0.02). At day 4 of the IL-2 cycle, serum TNF levels were significantly lower in the prednisone group compared to placebo group (9.4 vs 22.0 picograms/ml, respectively; p = 0.009), as were serum IL-6 levels (13.6 vs. 28.5 picograms/ml, respectively; p = 0.04). HIV-RNA decreased or remained undetectable in all patients, with no significant difference between the groups (p = 0.49). Conclusions: Although fewer grade 3 and 4 toxicities are observed in rIL-2 recipients receiving prednisone, this trend does not permit higher rIL-2 dosing. In addition, rIL-2-associated CD4+ cell count increases are significantly blunted by prednisone coadministration. This blunting of toxicities and immunologic response is associated with decreased serum proinflammatory cytokine levels.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Adult
• Anti-HIV Agents
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes
• Drug Toxicity
• HIV
• HIV Infections
• HIV Protease Inhibitors
• HIV Seropositivity
• Humans
• Interleukin-2
• Longitudinal Studies
• Prednisone

Other ID:

• GWAIDS0006635

UI: 102244131

From Meeting Abstracts