title: Decay characteristics of HIV-1-infected compartments during combination therapy.
abstract: Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t1/2) of < or =6 hours and loss of productively infected cells with a t1/2 of 1.6 days. Here we show that with combination therapy this initial decrease is followed by a slower second-phase decay of plasma viraemia. Detailed mathematical analysis shows that the loss of long-lived infected cells (t1/2 of 1-4 weeks) is a major contributor to the second phase, whereas the activation of latently infected lymphocytes (t1/2 of 0.5-2 weeks) is only a minor source. Based on these decay characteristics, we estimate that 2.3-3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments. To eradicate HIV-1 completely, even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, New Mexico 87545, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Perelson
authors.forename: P
authors.initials: P
authors.lastname: Essunger
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Vesanen
authors.forename: A
authors.initials: A
authors.lastname: Hurley
authors.forename: K
authors.initials: K
authors.lastname: Saksela
authors.forename: M
authors.initials: M
authors.lastname: Markowitz
authors.forename: D D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008433:Mathematics; D008954:Models, Biological; D019888:Nelfinavir; D011533:Proviruses / Q000502:physiology; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013451:Sulfonic Acids / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia; D017735:Virus Latency; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007546:Isoquinolines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013451:Sulfonic Acids; D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir