649 Interleukin-2 in Conjunction with HAART in Early HIV Infection Increases Na´ve and Memory CD4 Cells and Lowers Activation Markers F. M. Hecht, C. B. Hare*, M. S. McGrath, L. Liu, R. L. Gascon, J. O. Kahn, J. A. Levy Univ of California at San Francisco
Background: We examined immunologic and virologic markers when Interleukin-2 (IL-2) was added to HAART in the treatment of early HIV infection.
Methods: Subjects started on Combivir + nelfinavir or other HAART within 12 months (mos) of HIV infection. Once HIV-1 RNA was < 500 copies/mL, subjects were randomized to add IL-2 immediately or delayed by 48 wks. IL-2 was administered 7.5 million units SQ BID for 5 days every 8 wks for 6 cycles. HIV-1 RNA was quantitated by bDNA 3.0 (Bayer), and flow cytometry was performed to measure CD4 na´ve (RA+) and memory (RO+) cells and CD4 and CD8 activation (CD38+).
Results: Of 62 subjects, 29 were randomized to early IL-2 and 33 to delayed IL-2. To date, 31 subjects have completed all 6 cycles of IL-2 (19 in the early IL-2 group and 12 in the delayed IL-2 group). There were no baseline differences between groups in age, gender, ethnicity, HIV risk factors, time to initiation of HAART, CD4 count, HIV-1 RNA, or CD4/CD8 activation. From randomization to wk 48, median CD4 cell activation (CD38+) declined from 38.9 mean fluorescent intensity units (IQ range, 15.0-57.8) to 5.5 (2.6-7.1) in the early IL-2 group, and from 38.1 (23.3-43.7) to 19.0 (7.1-29.5) in the delayed IL-2 group (difference between groups, p = 0.008). Median CD8 cell activation (CD38+) declined from 52.8 (25.0-98.7) to 1.0 (1.0-5.1) in the early IL-2 group, and 115 (59.5-257) to 3.7 (1.0-14.3) in the delayed IL-2 group (difference between groups, p = 0.12). Comparing baseline to wk 12 of IL-2, the mean change in the percentage of na´ve (RA+) and memory (RO+) CD4 cells was +2.1% (range -17 to +16) and +0.8% (-18 to +17), respectively. Forty-eight (48) weeks after starting IL-2, median CD4 count increased from 645 cells/mL (IQ range, 520-918) to 1,326 (945-2,142) in the early IL-2 group and from 629 (540-714) to 1,431 (1,160-1,771) in the delayed IL-2 group (difference between groups, p = 0.81), and HIV-1 RNA was < 50 copies/mL in 79% and 92% of subjects in the early and delayed IL-2 groups, respectively (p = 0.62).
Conclusions: Subjects exhibited a similar rise in CD4 counts with no differences in HIV suppression when IL-2 was added to HAART in early HIV infection, whether IL-2 was initiated immediately after viral suppression or delayed by 48 wks. Na´ve and memory CD4 cells were increased in equal proportions after IL-2 administration. CD4/CD8 activation declined on HAART with or without IL-2. CD4 activation declined to a greater extent when IL-2 was administered.