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 owi...

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Veröffentlicht in:Nature (London) 1997-05, Vol.387 (6629), p.188-191
Hauptverfasser: Perelson, Alan S, Essunger, Paulina, Cao, Yunzhen, Vesanen, Mika, Hurley, Arlene, Saksela, Kalle, Markowitz, Martin, Ho, David D
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container_end_page 191
container_issue 6629
container_start_page 188
container_title Nature (London)
container_volume 387
creator Perelson, Alan S
Essunger, Paulina
Cao, Yunzhen
Vesanen, Mika
Hurley, Arlene
Saksela, Kalle
Markowitz, Martin
Ho, David D
description 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.
doi_str_mv 10.1038/387188a0
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subjects AIDS/HIV
Anti-HIV Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiretroviral agents
Antiviral agents
Biological and medical sciences
CD4-Positive T-Lymphocytes - virology
Decay
Drug therapy
Drug Therapy, Combination
Half-Life
HIV
HIV Infections - drug therapy
HIV Infections - virology
HIV Protease Inhibitors - therapeutic use
HIV-1 - physiology
Human immunodeficiency virus
human immunodeficiency virus 1
Humans
Isoquinolines - therapeutic use
Lamivudine - therapeutic use
Leukocytes, Mononuclear - virology
Lymphocytes
Macrophages - virology
Mathematics
Medical research
Medical sciences
Models, Biological
Nelfinavir
Pharmacology. Drug treatments
Proviruses - physiology
Reverse Transcriptase Inhibitors - therapeutic use
RNA, Viral - blood
Sulfonic Acids - therapeutic use
Viral Load
Viremia
Virus Latency
Zidovudine - therapeutic use
title Decay characteristics of HIV-1-infected compartments during combination therapy
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