HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection
Figure 6
Selective advantage of the ‘D67N/K70R/T215Y/K219Q’ mutant against the wild type during RNA- and DNA-dependent polymerization in the presence of AZT-TP.
The solid lines (green = activated cells, blue = unstimulated
cells, red = macrophages) indicate the selection parameter
, defined in eq. (4), for different levels of intracellular ATZ-TP during RNA- and DNA dependent polymerization (Panels A & B) of a random sequence of length 500 with 25% respective dNTP content. The light grey area indicates the in vivo concentrations range of AZT in purified circulating
T-cells from [71], converted to units
by assuming a cell volume of
for resting
T-cells [72]. The dashed horizontal line indicates the threshold for resistance selection, i.e.
. All utilized parameters are indicated in Table 1 and Tables S1, S2, S3 (supplementary material).