Lymph node architecture preceding and following 6 months of potent antiviral therapy: follicular hyperplasia persists in parallel with p24 antigen restoration after involution and CD4 cell depletion in an AIDS patient

Objectives: To evaluate changes in architecture, viral RNA, and viral prote in over 6 months in lymph nodes from retroviral-naive HIV-infected persons before and after commencing highly active antiretroviral therapy (HAART). Methods: Nine antiretroviral-naive HIV-infected persons had lymph nodes exc ised at baseline and at 2 and 6-8 months after beginning a four-drug combin ation regimen containing zidovudine, lamivudine, nevirapine, and indinavir. Two patients had AIDS. Lymph nodes were examined by immunohistochemical st aining for Gag p24 HIV, CD3, CD21, CD20, HAM 56, and Ki67 antigens and by i n-situ hybridization (ISH) for HIV RNA and H3-histone RNA. Results: Eight of nine baseline lymph nodes showed follicular hyperplasia a nd germinal center and paracortical mononuclear cell activation. At 2 month s, the lymph nodes from seven patients, including the AIDS patients, showed more follicular hyperplasia and activation than their baseline specimens b ut with decreased mononuclear cell activation. By 6 months, seven lymph nod es were less hyperplastic and activated than their corresponding 2 month sp ecimens. Combined ISH/immunohistochemical staining of baseline lymph nodes revealed productively infected T (CD3) and B (CD20) cells and macrophages ( HAM56+). HIV RNA-positive mononuclear cells were infrequent at 2 months, an d rare at 6 months. HIV RNA was still associated with follicular dendritic cells (FDC) at 2 months, but not at 6 months. HIV p24-positive antigen in g erminal centers persisted through all 6, and the one 8 month specimens. The baseline lymph nodes from one of the AIDS patients was involuted and T cel l depleted, whereas the follow-up lymph nodes were hyperplastic with normal T cell levels. Conclusion: Follicular hyperplasia and cell activation, possibly caused by persistent viral protein in germinal centers, may help explain why HIV vire mia rebounds so rapidly after the interruption of HAART. Restoration of arc hitecture may follow the treatment of patients with AIDS who initially had involuted and CD4 cell-depleted lymph nodes. (C) 1999 Lippincott Williams & Wilkins.