Pw. Nelson et al., Effect of drug efficacy and the eclipse phase of the viral life cycle on estimates of HIV viral dynamic parameters, J ACQ IMM D, 26(5), 2001, pp. 405-412
Fits of mathematic models to the decline in HIV-1 RNA after antiretroviral
therapies have yielded estimates for the life span of productively infected
cells of 1 to 2 days. In a previous report, we described the mathematic pr
operties of an extended model that accounts for imperfect viral suppression
and the eclipse phase of the viral life cycle (the intracellular delay bet
ween initial infection and release of progeny virions). In this article, we
fit this extended model to detailed data on the decline of plasma HIV-1 RN
A after treatment with the protease inhibitor ritonavir. Because the therap
y in this study was most likely not completely suppressive, we allowed the
drug efficacy parameter to vary from 70% to 100%. Estimates for the clearan
ce rate of free virus, c, increased with the addition of the intracellular
delay (as reported previously) but were not appreciably affected by changes
in the drug efficacy parameter. By contrast, the estimated death rate of v
irus-producing cells, delta, increased from an average of 0.49 day(-1) to 0
.90 day(-1) (an increase of 84%) because the drug efficacy parameter was re
duced from 100% to 70%. Neglecting the intracellular delay, the comparable
increase in delta was only about 55%. The inferred increases in delta doubl
ed when the model was extended to account for possible increases in target
cell densities after treatment initiation. This work suggests that estimate
s for delta may be greater than previously reported and that the half-life
of a cell in vivo that is producing virus, on average, may be 1 day.