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Session 71 Poster Session IL-2 and Other Forms of Immunotherapy Session Time: 4:30-6:30 pm Room 4E-F

523-M. The Effects of GM-CSF on Plasma HIV-1 RNA and CD4 Lymphocyte Counts in HIV-1-Infected Subjects Receiving Concomitant Potent Antiretroviral Therapy J. Jacobson*1, M. Lederman2, J. Spritzler3, H. Valdez2, P. Tebas4, G. Skowron5, R. Wang3, J. B. Jackson6, L. Fox7, and M. Gilbert8 for the ACTG 5041 Team 1Mount Sinai Sch. of Med., New York, NY; 2Case Western Reserve Univ., Cleveland, OH; 3Harvard Univ., Boston, MA; 4Washington Univ. Sch. of Med., St. Louis, MO; 5Brown Univ., Providence, RI; 6Johns Hopkins Univ. Sch. of Med., Baltimore, MD; 7NIH, Bethesda, MD; and 8Immunex Corp., Seattle, WA Background: Earlier studies reported improvements in plasma HIV RNA levels and CD4 lymphocyte counts in patients with HIV infection after treatment with GM-CSF. Methods: In ACTG 5041, 116 patients were enrolled in a randomized, double-blind, placebo-controlled evaluation of 16 weeks of GM-CSF (250 µg sc 3 times per week), followed by open-label treatment for an additional 32 weeks. Patients had stable baseline plasma HIV RNA levels >1500 copies/mL, and stayed on a constant antiretroviral regimen through at least the first 16 weeks. Subjects were stratified by screening CD4 lymphocyte counts (>200 cells/mm3 [n = 62] or <200 cells/mm3 [n = 54]). The primary endpoint was the change in plasma HIV RNA level from baseline to week 16; secondary analyses were immunologic. Analyses were on-treatment. Results: In the >200 CD4 cell and <200 CD4 cell strata, baseline median plasma HIV RNA levels were 3.81 log copies/mL and 4.46 log copies/mL, respectively. After 16 weeks, the placebo group tended to have greater median decreases in plasma HIV RNA than the GM-CSF group (-0.058 log vs +0.259 log copies/mL, p = 0.20, > 200 CD4 cell stratum; -0.227 log vs -0.014 copies/mL, p = 0.086, <200 CD4 cell stratum; -0.103 log vs +0.048 log copies/mL, p = 0.036, post hoc, combined strata). There were trends toward increases in CD4 cell counts with GM-CSF treatment (29 vs -8 cells/mm3, p = 0.20, >200 CD4 cell stratum; 5 vs -5 cells/mm3, p = 0.22, <200 CD4 cell stratum; 14 vs -6 cells/mm3, p = 0.06, combined strata). CD8 lymphocytes also increased (158 vs 1 cell/mm3, p = 0.083, >200 CD4 cell stratum; 48 vs -71 cells/mm3, p = 0.028, <200 CD4 cell stratum). In the <200 CD4 cell stratum, the median naïve CD4 cell increase was 1 vs -4 cells/mm3 (p = 0.034) and the median naïve CD8 cell increase was 1 vs -27 cells/mm3 (p = 0.091) in the GM-CSF and placebo groups respectively. Conclusions: Short-term GM-CSF administration modestly, but not significantly, increased HIV replication and CD4 cell counts among HIV-infected persons with incompletely controlled HIV replication. The relative preservation of naïve phenotype cells by GM-CSF in the <200 CD4 cell stratum suggests that bone marrow output may limit T-cell production in advanced HIV disease and that this can be ameliorated by GM-CSF. The durability and magnitude of the effect on CD4 cells, particularly naïve phenotype cells, will be determined by the longer administration of GM-CSF.

©2002 9th Conference on Retroviruses and Opportunistic Infections