Decay characteristics of HIV-1-infected compartments during combination therapy

Alan S. Perelson, Paulina Essunger, Yunzhen Cao, Mika Vesanen, Arlene Hurley, Kalle Saksela, Martin Markowitz and David D. Ho
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Alan S. Perelson: Los Alamos National Laboratory
Paulina Essunger: Los Alamos National Laboratory
Yunzhen Cao: Los Alamos National Laboratory
Mika Vesanen: Los Alamos National Laboratory
Arlene Hurley: Los Alamos National Laboratory
Kalle Saksela: Los Alamos National Laboratory
Martin Markowitz: Los Alamos National Laboratory
David D. Ho: Los Alamos National Laboratory

Nature, 1997, vol. 387, issue 6629, 188-191

Abstract: 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)1–3. The concentration of HIV-1 in plasma drops by ∼99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t1/2) of ≤6 hours and loss of productively infected cells with a t1/2 of 1.6 days3. 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 (t1/2of1–4weeks) 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.

Date: 1997
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DOI: 10.1038/387188a0

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