HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection
Figure 7
Selective advantage of intermediate viral mutants of the Q151M-complex during DNA-dependent polymerization in the presence of TFV-DP.
Dashed blue-, solid green- and dotted magenta line indicate the selective advantage of the Q151M, the multi-drug resistant Q151M-complex (Q151Mc: A62V/V75I/F77L/F116Y/Q151M) and the Q151Mc+K70Q mutation during DNA-dependent polymerization of a random sequence of length 500 with 25% respective dNTP content in unstimulated cells. The light grey area indicates the in vivo concentrations range of TFV-DP from [56], [71], [73], 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.
. Panel A: Selective advantage of the respective mutants with regard to wild type
. B: Selective advantage of a succeeding mutants with regard to progenitor in Q151M complex formation
. All utilized parameters are indicated in Table 1 and Tables S1, S2 (supplementary material).