Viral dynamics in vivo: limitations on estimates of intracellular delay and virus decay.
Anti-viral drug treatment of human immunodeficiency virus type I (HIV-1) and hepatitis B virus (HBV) infections causes rapid reduction in plasma virus load. Viral decline occurs in several phases and provides information on important kinetic constants of virus replication in vivo and pharmacodynamical properties. We develop a mathematical model that takes into account the intracellular phase of the viral life-cycle, defined as the time between infection of a cell and production of new virus particles. We derive analytic solutions for the dynamics following treatment with reverse transcriptase inhibitors, protease inhibitors, or a combination of both. For HIV-1, our results show that the phase of rapid decay in plasma virus (days 2-7) allows precise estimates for the turnover rate of productively infected cells. The initial quasi-stationary phase (days 0-1) and the transition phase (days 1-2) are explained by the combined effects of pharmacological and intracellular delays, the clearance of free virus particles, and the decay of infected cells. Reliable estimates of the first three quantities are not possible from data on virus load only; such estimates require additional measurements. In contrast with HIV-1, for HBV our model predicts that frequent early sampling of plasma virus will lead to reliable estimates of the free virus half-life and the pharmacological properties of the administered drug. On the other hand, for HBV the half-life of infected cells cannot be estimated from plasma virus decay.
Herz
A V
AV
Department of Zoology, University of Oxford, United Kingdom.
Bonhoeffer
S
S
Anderson
R M
RM
May
R M
RM
Nowak
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008433:Mathematics; D008962:Models, Theoretical; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors