465 The Persistence of Morphological and T-lymphocyte Subsets Abnormalities in Lymphoid Tissue in HIV-1 Infected Patients Successfully Treated with HAART Correlate with Lymphoid Tissue Viral Replication L. Alós, V. Morente, F. García*, M. Caballero, G. Mestre, A. Cruceta, M. Arnedo, T. Pumarola, M. Plana, T. Gallart, E. Martínez, J. Mallolas, J. L. Blanco, J. M. Miró, J. M. Gatell Inst d'Investigacions Biomèdiques August Pi i Sunyer, Hosp Clín, Univ of Barcelona, Spain
Background: Patients (pts) successfully treated with HAART still have abnormalities in lymphoid tissue (LT). A complete lymph node recovery may not be possible or may be linked to a persistence of viral replication.
Methods: Fourteen (14) HIV-infected persons in early stages (baseline lymphocytes T CD4+ > 500) treated with HAART for 1 yr and with sustained PVL below 20 c/ml. Tonsil biopsies were performed before and after 1 yr of HAART. Lymphoid tissue viral load (LTVL) was determined, and histological analyses and immunohistochemical procedures were performed using the antibodies HIV-1 p24, CD20, CD21 (FDC, follicular dendritic cells), CD4, CD8, Cytotoxic T-lymphocytes (CTL, granzyme B). The mean cell count per HPF was calculated. The LT morphology was graded: I: follicular hyperplasia; II: follicular regression; III: absence of follicles. The expression of HIV-1 p24 protein was graded, 0: negative; 1: scattered and scarce positive cells; 2: small groups of positive cells with mild intensity; 3: extensive and intense positive cells. Five (5) tonsils of non HIV-infected persons were controls.
Results: Before treatment, 8 cases (57%) were in histological stage III and the immunoexpression of p24 antigen was extense and intense (grade 3) in 12 cases (86%). The CD4 and CD8 T-cell counts were 286 and 276 x HPF, respectively. The mean percentage of CTL was 73%. After treatment, 8 cases were in histological stage II (57%) and 6 in stage I (43%), and the immunoexpression of p24 antigen was positive in 8 cases (57%) (6 cases in grade 2 and 2 in grade 1), mainly in FDC. After treatment, a significant increase of CD4 T-cells and decrease of CD8 T-cells and CTL (463 and 148 x HPF and 39%, respectively) was evidenced. The tonsil LT of non-HIV persons had a higher count of CD4 (638 x HPF), and a lower count of CD8 (96 x HPF) and CTL (28%), than the LT of HIV-infected persons, even after treatment. The morphological parameters and lymph tissue T-cell subsets in HIV-1 infected pts after 1 yr of HAART were significantly correlated with LTVL and the immunoexpression of p24 protein.
Conclusions: Lack of complete suppression of viral replication in LT may be the cause of the persistence of abnormalities in LT.
