Complex patterns of viral load decay under antiretroviral therapy: influence of pharmacokinetics and intracellular delay.
We present a model of HIV dynamics under antiretroviral therapy that combines drug pharmacokinetics and intracellular delay. A two compartment pharmacokinetic model is employed to determine the time evolution of the intracellular concentrations of the active forms of drugs, and thereby drug efficacy. The viral replication period is divided into pre- and post-drug action parts, allowing for the introduction of an intracellular delay in drug action. The standard model of viral dynamics is modified to account for the drug dependence of intracellular delay and continuously varying drug efficacy. Model calculations reveal that viral load decay in HIV infected patients under monotherapy can exhibit remarkably complex patterns depending on the relative magnitudes of the pharmacokinetic, intracellular, and intrinsic viral dynamic time-scales. The commonly assumed exponential decay is only a special case. However, uncertainties in measurement and the low sampling frequencies employed in present clinical studies preclude the identification of these patterns from existing clinical viral load data.
Dixit
Narendra M
NM
Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, MS K710, Los Alamos, NM 87545, USA.
Perelson
Alan S
AS
D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068698:Tenofovir; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir