title: HIV-1 dynamics after transient antiretroviral therapy: implications for pathogenesis and clinical management.
abstract: Simple models of CD4 lymphocyte interactions with human immunodeficiency virus (HIV) lead to the hypothesis that progression of HIV infection involves an increase in viral replicative capacity, due either to changes in the virus or in the host environment, or both. In order to consider how changes in plasma virus load after transient, potent antiretroviral therapy can be used to test the above hypothesis--a simple mathematical model that encompasses the processes of (1) arrival of new CD4 lymphocytes, (2) death/removal of these cells by HIV-independent mechanisms, (3) infection of susceptible CD4 lymphocytes by HIV, and (4) death/removal of infected cells was investigated. This showed that the in vivo rate of increase in plasma virus load immediately after transient therapy provides a measure of the viral replicative capacity. Thus, the hypothesis that progression of HIV infection involves an increase in viral replicative capacity can be tested by measuring this viral growth rate in patients with high CD4 counts and in patients with low CD4 counts. Studies should thus investigate dynamics of changes in virus levels after stopping antiretroviral therapy and, in particular, measure rates of increase in virus in patients at high and low CD4 counts. In practice, such data may assist in therapeutic management of patients with HIV infection.
authors.affiliation: Department of Primary Care and Population Sciences, Royal Free Hospital of Medicine, London, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: McLean
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Tyrer
authors.forename: V
authors.initials: V
authors.lastname: Emery
authors.forename: P
authors.initials: P
authors.lastname: Griffiths
authors.forename: M
authors.initials: M
authors.lastname: Bofill
authors.forename: G
authors.initials: G
authors.lastname: Janossy
authors.forename: C
authors.initials: C
authors.lastname: Loveday
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008432:Mathematical Computing; D008954:Models, Biological; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents