POSTMORTEM LOCALIZATION OF HIV-1 RNA BY INSITU HYBRIDIZATION IN LYMPHOID-TISSUES OF INTRAVENOUS DRUG-ADDICTS WHO DIED UNEXPECTEDLY

The histopathological alterations in lymphoid tissues and the presence of human immunodeficiency virus (HIV-1) RNA were studied in 25 consecutive autopsies of seropositive, apparently asymptomatic, intravenous drug overdose victims without palpable lymphadenopathy. The majority of lymphoid tissues in a given person showed either a combination of follicular hyperplasia and fragmentation or a combination of involution and depletion. Individuals with involuted and depleted lymphoid tissues were significantly older than those individuals with hyperplasia and fragmentation of follicles. Lymph nodes from individuals with hyperplasia with or without fragmentation were slightly but significantly larger than control nodes from seronegative persons. In tissues from infected cases, HIV-1 RNA was demonstrated by in situ hybridization in 49% of follicular centers showing hyperplasia, 62% of hyperplastic fragmented follicles, and 66% of involuted follicles in a distribution of follicular dendritic cells. No signal was detected in tissues demonstrating follicular depletion or nodes from seronegative persons. Scattered inter- and intrafollicular lymphoid cells with positive signal were present only in nodal tissues with follicular hyperplasia without involution. Tonsils, inguinal, axillary, mediastinal, supraclavicular, mesenteric nodes, and spleen were positive for HIV-1 RNA in 78%, 76%, 67%, 65%, 58% 50%, and 28% of cases, respectively, and the prevalence of positivity reflected the presence of follicles. We conclude that the clinically asymptomatic period of HIV-1 infection is characterized by pathological stages in lymphoid tissues that have distinct histological alterations and distribution of viral RNA.