347   Extended Therapy with Subcutaneous Interleukin-2 (scIL-2) in HIV-Infection: Long- Term Follow-Up of 3 Trials.

D. Chaitt*¹, J. Metcalf², J. Kovacs¹, J. Falloon², M. Polis², J. Tavel², H. Masur¹, C. Lane², and R. Davey².
¹The Clin. Ctr., NIH and²NIAID, NIH, Bethesda, MD.

Background:Numerous phase I-II trials have established that the combination of scIL-2 and antiretroviral therapy (ART) is capable of inducing substantial CD4 cell increases in HIV-infected patients. To examine the long-term feasibility and durability of this approach, we studied all patients continuing in active follow-up in longitudinal studies of scIL-2 therapy at our center.

Methods:Evaluable patients were those participating in the ongoing extension phases of 3 separate, prospective trials of scIL-2 plus ART in either moderate (2 trials, entry CD4>200) or early (1 trial, entry CD4>500) stage disease. In each trial, treatment continued with intermittent 5-day cycles of scIL-2 at whatever doses and frequencies were required to maintain CD4 counts substantially above baseline.

Results:Of 97 patients originally enrolled between 1993—1997, 73 entered the extension phases of these trials and 63 (100% male, mean age = 42 years) remain on active follow-up. The mean duration of study participation for these 63 patients is 4.6 (range: 3.4 —7) years. Their mean CD4 cell count and CD4% rose from values of 532 cells/µL and 27% at study entry to present levels of 1030 cells/µl and 40%, respectively. The mean number of scIL-2 cycles required to achieve and maintain these increases was 10 (range: 3—28) cycles. Patients tolerated a mean total daily scIL-2 dose of 11.9 (range: 3.0—15.0) million IU during their most recent cycle. The mean interval since the last cycle was 31 (range: 7—60) months. No AIDS-defining OIs have occurred in this cohort. For the 56 of 63 patients for whom viral load data are available, median plasma virus levels dropped from a baseline of 3.40 log₁₀copies/ml to 1.69 log₁₀copies/ml.

Conclusion:Long-term scIL-2 therapy is well tolerated and capable of maintaining CD4 cell increases for an extended period. Following initial induction of the CD4 response, patients are able to maintain these responses with a low frequency of intermittent scIL-2 therapy. These observations provide a compelling rationale for inclusion of scIL-2 in long-term treatment.