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Model of HIV-1 Disease Progression Based on Virus-Induced Lymph Node Homing and Homing-Induced Apoptosis of CD4+ Lymphocytes

Kirschner, Denise; Webb, G. F.; Cloyd, Miles
JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2000
CLINICAL SCIENCE: PDF Only

Several proposed theories have described the progression of HIV infection. Even so, no concrete evidence supports any as comprehensive, including, for example, why the CD4+ T-cell counts fall from 1000/mm3 of blood to roughly 100/mm3 over an average 10-year period, whereas concomitant viral loads are relatively constant, increasing by several orders of magnitude in late-stage disease. Here, we develop and validate a theoretical model that altered lymphocyte circulation patterns between the lymph system and blood due to HIV-induced enhanced lymph-node homing and subsequent apoptosis of resting CD4+ T cells can explain many aspects of HIV-1 disease progression. These results lead to a recalculation of the CD4+ lymphocyte dynamics during highly active antiretroviral therapy, and also suggest new targets for therapy.

Address correspondence and reprint requests to Denise Kirschner, Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, U.S.A.; email: kirschne@umich.edu.

Manuscript received February 2, 2000; accepted April 24, 2000.

© 2000 Lippincott Williams & Wilkins, Inc.