HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

Science. 1996 Mar 15;271(5255):1582-6. doi: 10.1126/science.271.5255.1582.

Abstract

A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t 1/2 = 1.6 days), and plasma virions were estimated to have a mean life-span of 0.3 days (t 1/2 = 0.24 days). The estimated average total HIV-1 production was 10.3 x 10(9) virions per day, which is substantially greater than previous minimum estimates. The results also suggest that the minimum duration of the HIV-1 life cycle in vivo is 1.2 days on average, and that the average HIV-1 generation time--defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles--is 2.6 days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also theoretical principles to guide the development of treatment strategies.

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

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Survival
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Half-Life
  • Humans
  • Kinetics
  • Models, Biological
  • RNA, Viral / blood
  • Regression Analysis
  • Ritonavir
  • Thiazoles / administration & dosage
  • Thiazoles / therapeutic use
  • Valine / administration & dosage
  • Valine / analogs & derivatives
  • Valine / therapeutic use
  • Viremia
  • Virion / drug effects
  • Virion / physiology*
  • Virus Replication

Substances

  • Antiviral Agents
  • HIV Protease Inhibitors
  • RNA, Viral
  • Thiazoles
  • Valine
  • Ritonavir