Abstract 406 - A Randomized, Controlled Pilot Study of HAART versus HAART plus IL-2 for the Treatment of Recently Acquired HIV Infection.

406 A Randomized, Controlled Pilot Study of HAART versus HAART plus IL-2 for the Treatment of Recently Acquired HIV Infection.

M. Dybul*, T. W. Chun, M. Belson, B. Hidalgo, B. Herpin, C. Perry, C. Hallahan, J. Metcalf, R. Davey, and A. S. Fauci.
NIAID, NIH, Bethesda, MD.

Background:Early antiretroviral therapy may preserve important HIV-specific immune responses. IL-2 may enhance these responses by peripherally expanding T cells. Enhanced immune responses may promote decreases in HIV tissue reservoirs. Therefore, early therapy with HAART or HAART + IL-2 may be useful to treat recently acquired HIV infection.

Methods:Patients with documented HIV infection occurring <6 months previously and a CD4⁺T cell count >300 cells/mm³were randomized to receive 4-drug HAART, or HAART plus subcutaneous IL-2 (3 cycles with a starting dosage of 7.5 mIU for 5 days every 8 weeks for 6 months) administered after achieving plasma HIV RNA <50 copies/ml. 5 patients received HAART alone, with plasma HIV RNA 5,650—>500,000 copies/ml and mean CD4⁺T cell count 528 cells/mm³(range 150—714) at diagnosis. 4 patients received HAART + 3 cycles of IL-2, with plasma HIV RNA 52,000—>750,00 and mean CD4⁺T cell count 580 cells/mm³(range 432—793) at diagnosis.

Results:While patients treated with HAART alone had a mean paired increase in CD4⁺T cells of 48% (549 at enrollment to 791 cell/mm³at 12 mos) and a 121% increase in naïve CD4⁺(CD45RO^-) T cells (70 to 138 cells/ mm³), patients treated with HAART + IL-2 had an increase in CD4⁺T cells of 277% (574 to 2042 cells/mm³) and an increase in naïve CD4⁺T cells of 1264% (52 to 507 cells/mm³). By regression analysis, HAART + IL-2 significantly increased CD4⁺T cells (p = 0.04) and increased naïve CD4⁺T cells (p = 0.07). Replication- competent HIV in resting CD4⁺T cells decreased in individuals treated with HAART alone from a median of 40.50 IUPM at baseline to 0.032 at 12 months versus 61.10 to 0.22 for the group treated with HAART + IL-2. Data will be presented on CD4⁺and CD8⁺HIV-specific immune responses.

Conclusion:While HAART plus intermittent IL-2 given to individuals with recent HIV infection results in a significant enhancement of CD4⁺T cells in the periphery, there is no change in replication-competent HIV in resting CD4⁺T cells compared with patients treated with HAART alone over a 12-month period of follow-up. Data on HIV-specific immune responses will be presented.