Estimates of intracellular delay and average drug efficacy from viral load data of HIV-infected individuals under antiretroviral therapy.
We analyse viral load data of five patients under ritonavir monotherapy using a model of HIV dynamics under antiretroviral therapy that includes both drug pharmacokinetics and the intracellular delay from the time of cell infection to viral production. Using this approach we separate pharamacokinetic from intracellular delays, and obtain new estimates of intracellular delay and the antiviral efficacy of ritonavir. We find the average intracellular delay to be 1 day, in agreement with experiments. The average viral generation time is now estimated at 2 days, resulting in approximately 180 replication cycles per year. The model also reveals that ritonavir monotherapy is approximately 65% as efficacious as a recently used potent four-drug therapy, suggesting that selection for drug resistance may be facilitated by the relatively low efficacy of individual drugs, contributing in part to the inherent limitations of current therapies in combating HIV-1 infection.
Dixit
Narendra M
NM
Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Markowitz
Martin
M
Ho
David D
DD
Perelson
Alan S
AS
D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019438:Ritonavir