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Session 70 Poster Session Thymic Function and Immune Reconstitution Session Time: 4:30-6:30 pm Room 4E-F

513-M. Growth Hormone Enhances Thymocyte Development and Induces Differentiation into Functional Peripheral T Cells in HAART Treated HIV-1+ Patients A. Pires*, J. Pido-Lopez, G. Moyle, B. Gazzard, F. Gotch, and N. Imami Imperial Coll. of Sci., Technology, and Med., Chelsea and Westminster Hosp., London, UK Background: Administration of human recombinant growth hormone (hrGH) with HAART in HIV-1 infection may increase thymic activity, resulting in the production of naïve T cells, and drive differentiation into functional peripheral memory/effector cells. Methods: 12 chronic HIV-1-infected individuals (mean age 43.4 ± 7.4 years) on HAART received rhGH. Viral load was undetectable in 10 patients and mean CD4 counts were 478.4 ± 192.7 cells/muL blood. We carried out 4-colour flow cytometry at baseline, 12 weeks post receiving 4mg/day of hrGH, and 24 weeks after randomisation into 3 groups (receiving placebo or, alternate day or, twice weekly dosing of hrGH). Parameters assessed were: naïve, memory and effector subsets based on CD45RA/CD27, CD45RO, and CCR7 expression, and activation marker CD38. T-cell receptor rearrangement excision circles (TREC) analysis was performed for all time points. Statistical analysis was carried out using a Mann-Whitney-U test. Results: At baseline, 4 patients showed a second, larger, activated subset of lymphocytes. 12 weeks post administration of hrGH, this was seen in 11 patients and consisted of >50% of T cells. This subset comprised mainly of memory lymphocytes, 80% and 53.4% of CD4+ and CD8+, respectively. There was an increase in the naïve compartment in the smaller subset, from 24.9% to 37% (p<0.01) and from 23.6% to 32% (p<0.01) in CD4+ and CD8+ cells, respectively. An emergence in memory/effector CD45RO+CCR7- in the larger lymphocyte subset, in both CD4+ and CD8+ T cells was observed. Changes in TREC levels correlated with phenotype in 5 patients. By week 24 all patients had undetectable TREC levels, which may be due to dilution by proliferative effector cells. The larger lymphocyte subset was sustained in 11 patients, the majority of these cells comprised of CD8+ T cells. A significant increase was seen in expression of CD38 on both CD4 and CD8 T cells to 68.9% and 71%, respectively, from baseline (p<0.01 for both). Conclusion: The use of hrGH appears to have a direct effect on thymic function, promotes thymocyte development resulting in an increase in naïve T cells, and induces differentiation into functional memory effector T cells.

©2002 9th Conference on Retroviruses and Opportunistic Infections