Decay Characteristics of HIV-1-infected Compartments During Combination Therapy

Nature. 1997 May 8;387(6629):188-91. doi: 10.1038/387188a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / virology*
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / physiology*
  • Half-Life
  • Humans
  • Isoquinolines / therapeutic use
  • Lamivudine / therapeutic use
  • Leukocytes, Mononuclear / virology
  • Macrophages / virology
  • Mathematics
  • Models, Biological
  • Nelfinavir
  • Proviruses / physiology
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Sulfonic Acids / therapeutic use
  • Viral Load
  • Viremia
  • Virus Latency
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Isoquinolines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Sulfonic Acids
  • Lamivudine
  • Zidovudine
  • Nelfinavir