510-M. Alteration of the IL-7 Homeostatic Response to T-Cell Depletion during the Course of HIV Infection

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

510-M.

Alteration of the IL-7 Homeostatic Response to T-Cell Depletion during the Course of HIV Infection
J. P. Routy *¹, G. Smith¹, R. Boulassel¹, N. Gilmore¹, M. Klein¹, J. MacLeod¹, R. LeBlanc¹, R. P. Sekaly², R. Cheynier², and R. Lalonde¹
¹McGill Univ. and ²Univ. de Montreal, QC, Canada

Background: Interleukin-7 (IL-7) is a potent stimulator of thymic and extra-thymic lymphopoiesis and enhances HIV replication in vitro. Several reports have shown a strong inverse correlation between IL-7 plasma levels and T-cell lymphopenia in advanced HIV-infected patients (CD4<200 cells/mm³). We assessed the relationship between IL-7 and plasma HIV-RNA, in acute and early infected (AEI) patients and in advanced patients.
Methods: Plasma IL-7 levels were measured longitudinally over 18 months in 35 seroconvertors (<6 months) using a highly sensitive ETA technique. Correlations between IL-7 levels, CD4, CD8, and viral load were analyzed according to response to antiretroviral therapy. These results were compared to chronically infected subjects (n = 70, median CD4 = 173/mm³, range: 1-670) during 1-year treatment.
Results: At baseline, higher levels of IL-7 were found in AEI patients (median 14.4 pg/mL, range: 5.1-28, median CD4 = 525/mm³. When compared to normal controls (median = 1.8 pg/mL, range: 0.4-3.6, p<0.0001), but no correlation was found between IL-7, CD3, CD4, and CD8 cell counts and HIV RNA (r = 0.13, p 0.66). Conversely, at months 3, 6, and 18 a progressive negative correlation was observed at each visit for CD3, CD4, and CD8 cell counts (r = -0.75, p<0.0001; r = -0.75, p<0.0001; r -0.36, p= 0.05, respectively). No correlation with plasma HIV RNA in successfully treated or untreated patients was observed during follow-up. A marked increase in IL-7 (>l5pg/mL) was observed in AEI patients with CD4 cell count <500/mm³ while the same IL-7 increase appeared for CD4 <100/mm³ in advanced patients.
Conclusions: Like in advanced HIV infection, IL-7 level is inversely correlated with CD4, CD8 depletion but is independent of viremia in both treated and untreated patients with AEI. High levels of IL-7 are associated with only mild decreases in CD4 cell count in early infection in contrast to what is observed in advanced patients. These findings are consistent with an alteration of IL-7 homeostatic response over the course of HIV infection.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections