Studies in Subjects with Long-Term Nonprogressive Human Immunodeficiency Virus Infection
Giuseppe Pantaleo, M.D., Stefano Menzo, M.D., Mauro Vaccarezza, M.D., Cecilia Graziosi, Ph.D., Oren J. Cohen, M.D., James F. Demarest, B.S., David Montefiori, Ph.D., Jan M. Orenstein, M.D., Cecil Fox, Ph.D., Lewis K. Schrager, M.D., Joseph B. Margolick, M.D., Ph.D., Susan Buchbinder, M.D., Janis V. Giorgi, Ph.D., and Anthony S. Fauci, M.D.
Background In a small percentage of persons infected with humanimmunodeficiency virus type 1 (HIV-1), there is no progressionof disease and CD4+ T-cell counts remain stable for many years.Studies of the histopathological, virologic, and immunologiccharacteristics of these persons may provide insight into thepathogenic mechanisms that lead to HIV disease and the protectivemechanisms that prevent progression to overt disease.
Methods and Results We studied 15 subjects with long-term nonprogressiveHIV infection and 18 subjects with progressive HIV disease.Nonprogressive infection was defined as seven or more yearsof documented HIV infection, with more than 600 CD4+ T cellsper cubic millimeter, no antiretroviral therapy, and no HIV-relateddisease. Lymph nodes from the subjects with nonprogressive infectionhad significantly fewer of the hyperplastic features, and noneof the involuted features, characteristic of nodes from subjectswith progressive disease. Plasma levels of HIV-1 RNA and theviral burden in peripheral-blood mononuclear cells were bothsignificantly lower in the subjects with nonprogressive infectionthan in those with progressive disease (P = 0.003 and P = 0.015,respectively). HIV could not be isolated from the plasma ofthe former, who also had significantly higher titers of neutralizingantibodies than the latter. There was viral replication, however,in the subjects with nonprogressive infection, and virus wasconsistently cultured from mononuclear cells from the lymphnodes. In the lymph nodes virus "trapping" varied with the degreeof formation of germinal centers, and few cells expressing viruswere found by in situ hybridization. HIV-specific cytotoxicactivity was detected in all seven subjects with nonprogressiveinfection who were tested.
Conclusions In persons who remain free of disease for many yearsdespite HIV infection the viral load is low, but viral replicationpersists. Lymph-node architecture and immune function appearto remain intact.
Source Information
From the Laboratory of Immunoregulation (G.P., S.M., M.V., C.G., O.J.C., J.F.D., A.S.F.) and the Division of AIDS (L.K.S.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; the Department of Medicine, Cellular Immunology, and Cytometry, UCLA School of Medicine, Los Angeles (J.V.G.); the Department of Surgery, Center for AIDS Research, Duke University Medical Center, Durham, N.C. (D.M.); the Department of Pathology, George Washington University, Washington, D.C. (J.M.O.); Molecular Histology, Inc., Gaithersburg, Md. (C.F.); the Department of Environmental Health Sciences, Department of Immunology and Infectious Diseases, Johns Hopkins School of Hygiene and Public Health, Baltimore (J.B.M.); the Research Branch, AIDS Office, Department of Public Health, San Francisco (S.B.); and the Institute of Microbiology, University of Ancona Medical School, Ancona, Italy (S.M.).
Address reprint requests to Dr. Pantaleo at the Laboratory of Immunoregulation, Bldg. 10, Rm. 11B13, 10 Center Dr., MSC 1876, Bethesda, MD 20892-1876.
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