Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load

Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunolog...

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Bibliographic Details
Published in:Blood 2004-08, Vol.104 (4), p.942-947
Main Authors: Deeks, Steven G., Kitchen, Christina M.R., Liu, Lea, Guo, Hua, Gascon, Ron, Narváez, Amy B., Hunt, Peter, Martin, Jeffrey N., Kahn, James O., Levy, Jay, McGrath, Michael S., Hecht, Frederick M.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Female
HIV Infections - immunology
Human viral diseases
Humans
Immune System - physiology
Infectious diseases
Kinetics
Lymphocyte Activation - immunology
Male
Medical sciences
Prospective Studies
RNA, Viral - blood
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Viral Load
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Summary:Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation“set point” is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4+ and CD8+ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviral-treated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8+ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8+ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8+ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4+ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4+ T cells are lost over time.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-09-3333