HIV Type 1 RNA Expression in Bone Marrows of Patients with a Spectrum of Disease

Abstract

HIV-1-infected individuals at various stages of disease harbor virus in their lymphoid organs, which serve as reservoirs of viral replication throughout the course of infection. Hematologic abnormalities are extremely common in HIV-1-infected individuals and occur at all stages of disease. To determine if the bone marrow is a reservoir of HIV-1 in vivo and if active HIV-1 RNA expression in that site is related to hematologic disease in infected individuals, we examined HIV-1 RNA expression in bone marrow biopsies from 37 patients with a broad spectrum of hematologic and HIV-1-related disease. To detect HIV-1 RNA expression, we performed in situ hybridization. Double-label in situ hybridization–immunohistochemistry was used for precise identification of the type of cell expressing viral RNA. Six of 37 (16%) patients demonstrated HIV-1 RNA expression in the bone marrow. Double-label analysis performed on two marrows localized HIV-1 RNA to cells of the macrophage lineage. Active HIV-1 expression correlated with advanced HIV-1-related disease and CD4 cell depletion rather than a specific hematologic or clinical diagnosis. These data suggest that although the bone marrow does not serve as a reservoir of viral expression throughout the course of infection as do the lymphoid organs, HIV-1-expressing cells are present in the bone marrow during late stages of disease. These data also suggest that hematologic abnormalities in the majority of infected individuals may result from indirect effects of HIV-1 such as cytokine dysregulation rather than HIV-1 expression in the bone marrow itself.