Analysis of a model for the pathogenesis of AIDS.

According to a previously proposed mathematical model, the pathogenesis of acquired immunodeficiency syndrome (AIDS) could be explained by two phenomena: direct human immunodeficiency virus (HIV) infection of CD4+ T-cell populations and ongoing generation and selection of HIV mutants with increasing replicative capacity. In the present paper, the results obtained with this model are described in more detail. For different values of biologically interpretable parameters, the model predicts very different patterns of CD4+ T-cell decline after primary infection. With the assumption of a variability of 10% to 25% of three parameters between infected individuals, the model yields a realistic distribution curve of the incubation period to AIDS.

[1]  B. Rocha,et al.  Lymphocyte lifespans: homeostasis, selection and competition. , 1993, Immunology today.

[2]  M. Somasundaran,et al.  Unexpectedly high levels of HIV-1 RNA and protein synthesis in a cytocidal infection. , 1988, Science.

[3]  D. Richman,et al.  A cross-sectional comparison of persons with syncytium- and non-syncytium-inducing human immunodeficiency virus. , 1993, The Journal of infectious diseases.

[4]  A. Fauci,et al.  The immunopathogenesis of human immunodeficiency virus infection. , 1993, The New England journal of medicine.

[5]  A. McLean,et al.  Lifespan of human lymphocyte subsets defined by CD45 isoforms , 1992, Nature.

[6]  J. Phair,et al.  A1, Cw7, B8, DR3 HLA antigen combination associated with rapid decline of T-helper lymphocytes in HIV-1 infection A report from the Multicenter AIDS Cohort Study , 1990, The Lancet.

[7]  Andrew N. Phillips,et al.  Reduction of HIV Concentration During Acute Infection: Independence from a Specific Immune Response , 1996, Science.

[8]  R. Coutinho,et al.  HIV‐1 biological phenotype in long‐term infected individuals evaluated with an MT‐2 cocultivation assay , 1992, AIDS.

[9]  J. Groopman,et al.  Characterization of Serum Netralization Response to the Human Immunodeficiency Virus (HIV) , 1987 .

[10]  R. V. van Lier,et al.  AIDS pathogenesis: a dynamic interaction between HIV and the immune system. , 1990, Immunology today.

[11]  Robin A. Weiss,et al.  How does HIV cause AIDS , 1993 .

[12]  F. Walshe The structure of medicine. , 1948, Lancet.

[13]  Martin A. Nowak,et al.  Viral dynamics in human immunodeficiency virus type 1 infection , 1995, Nature.

[14]  D. Ho,et al.  Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome , 1994, Journal of virology.

[15]  S. Vermund,et al.  Long-term survivors of HIV-1 infection: Definitions and research challenges , 1994 .

[16]  D Schenzle,et al.  A model for AIDS pathogenesis. , 1994, Statistics in medicine.

[17]  John W. Ward,et al.  1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. , 1993, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[18]  I. Keet,et al.  Prognostic Value of HIV-1 Syncytium-Inducing Phenotype for Rate of CD4+ Cell Depletion and Progression to AIDS , 1993, Annals of Internal Medicine.

[19]  J. Albert,et al.  REPLICATIVE CAPACITY OF HUMAN IMMUNODEFICIENCY VIRUS FROM PATIENTS WITH VARYING SEVERITY OF HIV INFECTION , 1986, The Lancet.

[20]  J. Spouge,et al.  Quantifying the infectivity of human immunodeficiency virus. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Kaslow,et al.  The role of the major histocompatibility complex in human immunodeficiency virus infection--ever more complex? , 1994, Journal of Infectious Diseases.

[22]  J. Phair Keynote address: variations in the natural history of HIV infection. , 1994, AIDS research and human retroviruses.

[23]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[24]  A. Perelson,et al.  HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time , 1996, Science.

[25]  D. Ho,et al.  Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression , 1994, Journal of virology.

[26]  F. de Wolf,et al.  Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV‐1 phenotype , 1992, AIDS.

[27]  J. Goedert,et al.  HLA phenotype is a factor in determining rate of disease progression and outcome in HIV-1-infected individuals. , 1992, AIDS Research and Human Retroviruses.

[28]  A. McLean,et al.  In vivo estimates of division and death rates of human T lymphocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  B. Walker,et al.  Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. , 1996, AIDS research and human retroviruses.