AEGiS-07CROI: Low-dose subcutaneous (SC) IL-2 in combination with HAART therapy induces significant increases in NK cells and naïve T-cells in patients with <300 CD4+ T-cells/mm<sup>3</sup>: results of a randomized controlled trial MA-9801.

3:ÿresultsÿofÿaÿrandomizedÿcontrolledÿtrialÿMA-9801.ý/Aþ ConfÿRetrovirusesÿOpportunisticÿInfectÿ2000ÿJanÿ30-Febÿ2;ÿ7:148ÿ(abstractÿno.ÿ381) > AEGiS-07CROI: Low-dose subcutaneous (SC) IL-2 in combination with HAART therapy induces significant increases in NK cells and naïve T-cells in patients with <300 CD4+ T-cells/mm<sup>3</sup>: results of a randomized controlled trial MA-9801.

7th Conference on Retroviruses and Opportunistic Infections

San Francisco, CA - January 30 -February 4, 2000

Low-dose subcutaneous (SC) IL-2 in combination with HAART therapy induces significant increases in NK cells and naïve T-cells in patients with <300 CD4+ T-cells/mm³: results of a randomized controlled trial MA-9801.

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:148 (abstract no. 381)

Lalazari J, Beal J, Ruane P, Cohen C, Jacobson E, Sundin D, Smith K; Quest Clin. Res, San Francisco, CA.

Recombinant IL-2 (Proleukin) is a pleotrophic T-cell growth factor that has been extensively tested in patients living with HIV. Studies to date have examined IL-2 given in an intermittent regimen at a dose of 9-15 MIU/day and results from these studies demonstrate significant increases in CD4+ T-cell counts with no deleterious impact on plasma HIV RNA. Patients were eligible for the study if they had a stable viral load of less then 500 copies/mm³ for more than 2 months and CD4 < 300 cells/mm³. Patients received either 6 months of SC IL-2 1.2 MIU/m²/day plus HAART or HAART alone. Dose reductions were allowed if grade 2 toxicities were encountered. 115 patients (56 IL-2 and 59 control) were enrolled. The most common side effects attributable to IL-2 included: local site reactions, flu like symptoms, asthenia, nausea and diarrhea. No significant differences in viral titers were noted in either group at 6 months. Statistically significant immunological changes were noted in the IL-2 arm. CD16+CD56+ (NK) lymphocytes rose a mean of 157 cells/mm³ vs. 20 cells/mm³ in the control arm (p< 0.001). While mean absolute change in CD4+ T- counts did not reach statistical significance in the IL-2 arm compared to the controls (61 cells vs. 35 cells, P = 0.095), CD4 percentage showed a 3.6% increase in the IL-2 arm vs. a 1.4% increase in controls (p< 0.001). Of interest there was a 4.8% increase in CD4+CD45RA+ cells and a 2.1% increase in CD8+CD45RA+ cells compared to a 0.4% and -1.7% change in the control patients respectively (p<0.001). These data support an IL-2 effect involving preferential expansion of the naïve lymphocyte population. This trial demonstrates that low-dose daily IL-2 is tolerable, has a significant impact upon NK cells and preferentially expands naïve T-cells at levels not seen in the control group. The clinical impact of these changes awaits further study.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Interleukin-2, Killer Cells, Natural, Antigens, CD4, T-Lymphocytes, CD4 Lymphocyte Count, Viral Load, HIV Infections, Anti-HIV Agents, HIV, Lymphocytes, Receptors, Interleukin-2, Antigens, CD45, Antigens, CD56, aldesleukin, Human, therapy, drug therapy, AIDS

2000-01-30
381

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