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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

521-M. Phase I Study of Anti-LFA-1 Monoclonal Antibody (Cytolin) in Adults with HIV Infection D. Northfelt*1, A. Allen2, and P. Kapustay2 1Univ. of California, San Diego and 2Amerimmune Pharmaceuticals, Woodland Hills, CA Background: Human lymphocyte function-associated antigen (LFA)-1 is a heterodimeric lymphocyte surface glycoprotein. LFA-1 is expressed on CD8+ cytotoxic T lymphocytes (CTLs) prevalent in HIV-infected individuals and may be involved in the progressive depletion of CD4+ T-cell counts. Anti-LFA-1 monoclonal antibodies (mAB) have been shown to reversibly inhibit CTL killing by slowing the initial rate of cytolysis and by interfering with effector/conjugate formation. Cytolin, a mouse anti-human mAB, is believed to bind 4 epitopes of the alpha region of LFA-1. This phase I single-dose study was designed to evaluate the safety and preliminary efficacy of 2 doses of Cytolin in HIV-infected adults. Methods: 13 HIV-infected men (plasma HIV RNA concentrations > 20,000 copies/mL, CD4+ T-cell counts 200-500 cells/mm3) were sequentially enrolled in 2 dose groups: 0.05 mg/kg (n=6) and 0.1 mg/kg (n=7). Cytolin was administered on day 0 by slow IV infusion (0.5 mg protein/minute). Hematologic, biochemical, and clinical adverse events (AE) were assessed at predetermined times after Cytolin administration. Preliminary efficacy assessment consisted of change from baseline in HIV RNA concentration, CD4+ and CD8+ T-cell counts. Parameters were analyzed with descriptive statistics. Results: All Aes were mild to moderate, and only 1 AE (diarrhea) was considered possibly related to study drug. In the 0.05-mg/kg dose group mean HIV RNA concentration was 0.265 log below baseline on day 14 and 0.363 log above baseline on day 56. Mean CD4+ T-cell count was 37.3 cells/mm3 above baseline on day 28 and 15 cells/mm3 below baseline on day 56. Mean CD8+ T-cell count fluctuated, and was 153.6 cell/mm3 below baseline on day 56. In the 0.1-mg/kg dose group, mean HIV RNA concentration was 0.153 log below baseline on day 14 and 0.229 log below baseline on day 56. Mean CD4+ T-cell count was 20.4 cells/mm3 below baseline on day 14, but 70.1 cells/mm3 above baseline on day 56. Mean CD8+ T-cell count fluctuated, and was 107.4 cell/mm3 above baseline on day 56. Conclusions: Cytolin was well tolerated. A single 0.1-mg/kg dose reduced HIV RNA concentration and increased CD4+ and CD8+ T-cell counts at 56 days. The data suggest a dose response relationship, and thus suggest that higher doses may be more effective.

©2002 9th Conference on Retroviruses and Opportunistic Infections