HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time.
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.
Perelson
A S
AS
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA.
Neumann
A U
AU
Markowitz
M
M
Leonard
J M
JM
Ho
D D
DD
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D002470:Cell Survival; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D019438:Ritonavir; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014766:Viremia; D014771:Virion / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013844:Thiazoles; D014633:Valine; D019438:Ritonavir