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
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.