Recovery of Lymphoid Tissue Architecture and CD4 Cell Count Could Be Limited by Fibrotic Changes in HIV+ Patients under Antiretroviral Treatment
A Diaz, A Mozos, F Garcia, M Caballero, A Martinez, JM Gatell, L Alos. Hospital Clinic, IDIBAPS, UB, Barcelona, Spain
Background: Although peripheral blood viral load and T-cell subsets are usually used for monitoring HIV infection, key pathogenesis events take place in lymphoid tissues. Lymphoid tissue (LT) indemnity is crucial for the immunological recovery in HIV-infected patients under highly active antiretroviral therapy (HAART). The aim of our study was to evaluate the changes of LT architecture and CD4+ cell counts in HIV patients receiving HAART.
Design: Tonsillar biopsies were performed in 7 patients with chronic asymptomatic HIV-1 infection before initiating HAART and 25 after receiving HAART for a long time (from 17 to 112 months). Five tonsillar resections of HIV-negative individuals were used as controls. From formalin-fixed and paraffin-embedded tissue we performed in each case H&E, Masson trichrome and immunostain for CD4 (Novocastra, 1F6). Quantitative image analysis was used to assess LT architecture, with the measurement of the proportion of LT occupied by follicular areas (FA), collagen deposition (fibrosis), and the mean interfollicular CD4+ cell count per m2.
Results: Before HAART, LT showed effacement of the architecture, with absence or small follicle structures (mean proportion of FA of 0.045). After initiating HAART, there was a recovery of LT architecture (mean FA of 0.157), which correlated with a significant increase of interfollicular CD4+ cells (p<0.001). However the CD4+ cell count did not reach the CD4+cell count of HIV- patients. We observed a higher proportion of fibrosis in tonsillar biopsies of patients receiving HAART (median 5%), compared to those from HIV- patients. We also found that the biopsies with a higher amount of fibrosis had a lower CD4+ cells, although this finding was not significant. There was a significant increase of LT fibrosis in patients receiving reverse transcriptase inhibitors when compared to those receiving protease inhibitors (p=0.029).
Conclusions: The treatment with HAART produces a significant recovery of LT architecture and CD4+ cells but it does not reach the CD4+ cell count of HIV- patients LT, even after a long time of treatment. We have found for the first time a higher amount of collagen deposition in LT of patients receiving reverse transcriptase inhibitors, compared to those receiving protease inhibitors. This fact could limit the immune recovery in these patients.
Monday, March 9, 2009 1:00 PM
Poster Session II # 185, Monday Afternoon