STUDIES IN SUBJECTS WITH LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Citation
G. Pantaleo et al., STUDIES IN SUBJECTS WITH LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION, The New England journal of medicine, 332(4), 1995, pp. 209-216
Citations number
35
Categorie Soggetti
Medicine, General & Internal
ISSN journal
00284793
Volume
332
Issue
4
Year of publication
1995
Pages
209 - 216
Database
ISI
SICI code
0028-4793(1995)332:4<209:SISWLN>2.0.ZU;2-B
Abstract
Background. In a small percentage of persons infected with human immun odeficiency Virus type 1 (HIV-1), there is no progression of disease a nd CD4+ T-cell counts remain stable for many years. Studies of the his topathological, virologic, and immunologic characteristics of these pe rsons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease. Methods and Results. We studied 15 subjects with long-t erm nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years o f documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lym ph nodes from the subjects with nonprogressive infection had significa ntly fewer of the hyperplastic features, and none of the involuted fea tures, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood m ononuclear cells were both significantly lower in the subjects with no nprogressive infection than in those with progressive disease (P = 0.0 03 and P = 0.015, respectively). HIV could not be isolated from the pl asma of the former, who also had significantly higher titers of neutra lizing antibodies than the latter. There was viral replication, howeve r, in the subjects with nonprogressive infection, and virus was consis tently cultured from mononuclear cells from the lymph nodes. In the ly mph nodes virus ''trapping'' varied with the degree of formation of ge rminal centers, and few cells expressing virus were found by in situ h ybridization. HIV-specific cytotoxic activity was detected in ail seve n subjects with nonprogressive infection who were tested. Conclusions. in persons who remain free of disease for many years despite HIV infe ction the Viral load is low, but viral replication persists. Lymph-nod e architecture and immune function appear to remain intact.