Patient Specificity and the difference in the half-life of
productively infected T-cells.
Patrick W. Nelson, John E. Mittler, and Alan S. Perelson
Fits of mathematical models for HIV
drug treatment dynamics to the decline in HIV-1 RNA following
antiretroviral therapies have yielded estimates for the life span of
productively infected cells of about 1.5 days. Subsequent models have
extended the analysis to account for imperfect viral suppression and
the presence of an intracellular delay (the eclipse phase of the viral
life cycle). The interactions between these factors, however, have
not previously been explored. Here we show that if drug is not
completely efficacious that the addition of an intracellular delay
will decrease the estimated lifespan of virus producing cells (while
increasing the expected lifespan of a cell that has just been
infected). When we fit this model to published data on the decline of
HIV-1 RNA following treatment with the protease inhibitor ritonavir,
the estimated death rate of virus producing cells increased from 0.5
day$^{-1}$ to 0.89 $^{-1}$ day as the efficacy parameter was reduced
from 100\% to 80\%. For efficacies in this range, the estimated
half-lives of the virus producing stage range from 0.8 to 1.4 days,
while the estimated viral generation times range from 2.1 to 3.3
days.