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Rapid Activation of Lymph Nodes upon Interrupting HAART in HIV-Infected Patients after Prolonged Viral Suppression J. M. ORENSTEIN*1, N. BHAT2, C. YODER3, C. FOX4, M. POLIS2, J. METCALF2, J. KOVACS3, J. FALLOON2, R. WALKER2, H. MASUR3, H. C. LANE2, and R. DAVEY2.
1George Washington Univ., Washington, DC; 2NIAID, Bethesda, MD; 3NIH Clin. Ctr., Bethesda, MD; and 4Molecular Histology Inc., Gaiithersburg, MD Objective: To compare the architecture, HIV-1 viral RNA, and protein expression in lymph nodes (LN) excised from individuals during chronic treatment with HAART to those removed following plasma virus rebound after HAART interruption.
Material and Methods: Five HIV-infected patients on HAART for at least one year, with CD4+ cell counts >600 cells/µL, and plasma HIV-1 RNA <50 copies/ml underwent an initial inguinal LN excision upon discontinuation of HAART and then a second LN biopsy following rebound of plasma virus. LN were evaluated by immunohistochemical staining, in situ hybridization, and transmission electron microscopy.
Results: LN at baseline while on HAART were quiescent to mildly hyperplastic and contained more primary than secondary follicles. They had no detectable follicular dendritic cell (FDC) associated HIV RNA or p24 protein and only rare mononuclear cells (MNC) expressing RNA (one LN) or p24 (two LN). Plasma virus at the time of the second LN biopsy 1-2 months following interruption of HAART ranged from 329 to 3.2 x 106 copies/ml. The CD4+ cell count decline ranged from 5-48% during this time interval and was greatest in those patients with the highest rebound in plasma viremia. Four of 5 of the second set of LN were more hyperplastic than the initial LN. The fifth showed paracortical hyperplasia but no germinal centers. MNC expression of HIV RNA in the second LN paralleled the level of plasma viremia. Increased cell activation (Ki67 and H3-histone) occurred consistently in the second LN. The 3 patients with the highest levels of HIV RNA in plasma had increased NK cells in their LN.
Conclusion: Quiescent LN from individuals on extended treatment with HAART rapidly become hyperplastic and activated following within one to two months of treatment interruption. Virus expression in LN MNC parallels the rebound in plasma viremia and fall in CD4 cells.
Key Words: HAART, Lymph nodes
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