Decay characteristics of HIV-1-infected compartments during combination therapy.
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.
Perelson
A S
AS
Theoretical Division, Los Alamos National Laboratory, New Mexico 87545, USA.
Essunger
P
P
Cao
Y
Y
Vesanen
M
M
Hurley
A
A
Saksela
K
K
Markowitz
M
M
Ho
D D
DD
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
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