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Low-Dose Subcutaneous (SC) IL-2 in Combination with HAART Therapy Induces Significant Increases in NK Cells and Naive T-cells in Patients with <300 CD4+ T-cells/mm3: Results of a Randomized Controlled Trial MA-9801 J. LALAZARI*1, J. BEAL2, P. RUANE3, C. COHEN4, E. JACOBSON5, D. SUNDIN6, K. SMITH5, and the MA9801 Study Group. 1Quest Clin. Res, San Francisco, CA; 2Assoc. Med/Mental Hlth., Tulsa, OK; 3Tower ID, Los Angeles, CA; 4Comm. Res. Initiative, Boston, MA; 5Cornell NY Hosp. and 6 Chiron, Emeryville, 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. Key Words: HIV, Interleukin-2 |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |