Am. J. Respir. Crit. Care Med., Volume 160, Number 6, December 1999, 2048-2055

Enhanced In Vivo Human Immunodeficiency Virus-1 Replication in the Lungs of Human Immunodeficiency Virus-Infected Persons with Pneumocystis carinii Pneumonia

HENRY KOZIEL, SUE KIM, CHRISTINE REARDON, XIUHONG LI, ROBERT GARLAND, PAULA PINKSTON, and HARDY KORNFELD

Divisions of Pulmonary and Critical Care Medicine, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston; and Division of Pulmonary and Critical Care, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts

The relationship of serum human immunodeficiency virus-1 (HIV-1) RNA levels to HIV-1 RNA levels in other compartments, such as the lungs, is not well characterized. The purpose of this study was to determine the viral burden of HIV-1 in the lungs by comparing HIV-1 RNA in cell-free bronchoalveolar lavage fluid (BALF) with that in serum. Specimens were examined from 77 HIV-seropositive adults (CD4⁺ cell counts: 0 to 700 cells/mm³; 48% receiving prescribed antiretroviral agents), comprising 43 asymptomatic individuals who were compared with 34 persons with active lung disease caused by Pneumocystis carinii (n = 26), bacteria (n = 3), Mycobacterium avium complex (n = 2), Nocardia sp. (n = 1), Aspergillus sp. (n = 1), or pulmonary Kaposi's sarcoma (n = 1). For serum HIV-1 RNA, the proportion of subjects with detectable levels and the mean values were similar for asymptomatic individuals and persons with active lung disease (85% versus 86%, respectively) (6.64 × 10⁴ versus 1.81 × 10⁵ HIV-1 RNA copies/ml; p = 0.13). In contrast, HIV-1 RNA in BALF was more often detected (16% versus 62%; p = 0.001), and mean values were higher (1.04 × 10⁵ versus 3.31 × 10⁶ HIV-1 RNA copies/ml; p = 0.032), in subjects with active lung disease than in asymptomatic subjects, independent of early or advanced clinical stages of HIV-related disease. For both study groups, HIV-1 RNA levels in BALF exceeded those in serum in 56% of cases by up to 66-fold, and did not correlate with local levels of tumor necrosis factor-, granulocyte-macrophage colony-stimulating factor, or interleukin-16. HIV-1 proviral DNA in cells from BALF was detected in up to 86% of subjects, more frequently in persons with advanced HIV disease (p = 0.0496), and often involved > 10% of BALF cells, but did not correlate with HIV-1 RNA detected in BALF. These data provide evidence for active HIV-1 replication in the lungs. HIV-1 replication is compartmentalized relative to serum, may be restricted, is independent of HIV-1 proviral DNA and clinical stage of HIV, and may be influenced by pulmonary disease such as P. carinii pneumonia or by other local or lung-specific factors. The lungs represent a large reservoir for HIV-1, and may present a source of persistent HIV-1 replication even during periods of apparent clinical latency of HIV-1 infection. Koziel H, Kim S, Reardon C, Li X, Garland R, Pinkston P, Kornfeld H. Enhanced in vivo human immunodeficiency virus-1 replication in the lungs of human immunodeficiency virus-infected persons with Pneumocystis carinii pneumonia.

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