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.