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Cytokine Activation in HIV+ Individuals Receiving IL-2 and Antiretrovirals. Results from a Randomized 4-Arms Trial C. FORTIS*, L. SOLDINI, S. GHEZZI, F. VEGLIA, S. NOZZA, G. TAMBUSSI, A. LAZZARIN, and G. POLI. San Raffaele Sci. Inst., Milano, Italy Sixty three HIV+ individuals with absolute CD4+ cell counts ranging between 200 and 500 cells/µl at the study entry were enrolled in a randomized phase II trial designed to compare 3 different regimens of IL-2 administration in combination with ART over 12 months. The treatment arms were: A. ART + continuous iv IL-2 (12 MU/die x5 days every 8 weeks x2 cycles), followed by high dose sc IL-2 (7.5 MU/bid x5 days every 8 weeks x4 cycles); B. ART + high dose sc IL-2 (7.5 MU/bid x5 days every 8 weeks x6 cycles); C. ART + low dose sc IL-2 (3 MU/bid x5 days every 4 weeks x12 cycles); D. ART alone. During IL-2 administrati- on serum concentrations of IL-2, sIL-2R, TNF-a, viremia, and phenotypic analysis of T lymphocyte subsets were investigated. In all IL-2 containing arms, a significant correlation among the variations of IL-2, sIL-2R and TNF-a serum concentrations were observed (0.0001< p <0.045). IL-2 peaked at the third day of each cycle and returned to the baseline during the intercycles, whereas sIL-2R peaked with a mean delay of 2 days compared to IL-2, but remained at levels significantly higher than baseline during the intercycles. In A and B arms, peak IL-2 levels tended to decrease whereas sIL-2R levels augmented; in contrast, in arm C IL-2 peak levels were unchanged despite an increase of sIL-2R. TNF-a peaked during IL-2 infusion with a tendency to increase in the last cycles in arms A and B, whereas it decrea- sed in arm C. Detectable levels of TNF-a were also found in the D group with a net increasing trend overtime. A steady increase in the absolute number and % of CD4+ lymphocytes was observed, with an inversion of the CD4/CD8 ratio reached earlier in arm C than in A and B. The % of CD4+ cells expressing CD25 Ag increased progressively during the study in individuals receiving IL-2. Conversely, HLA-DR molecules were mostly present on CD8+ cells, and decreased in individuals receiving IL-2, but increased in the D group. A positive correlation between the variations of circulating CD4+CD25+ and CD4+DR+ cells and the sIL-2R serum concentrations was observed (0.0001< p < 0.0008). In conclusion, low doses sc IL-2 induces the same immunological stimulations than high doses, but with reduced toxic effects. Key Words: cytokines, IL-2 therapy, immune modulation |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |