Figure 3. Dose response curves help explain the dynamics of treated viral populations.

(A) HIV antigen levels initially decline when treated with AZT monotherapy (6x200 mg/day) to below a detectable threshold (dotted line). Starting at week 16, the viral population begins to rebound even in the presence of the drug, indicating the evolution of drug resistance. (A) Is reprinted with annotations from Figure 1A from The Lancet, 1 (8582), Reiss et al, ‘Resumption of HIV antigen production during continuous zidovudine treatment’, Page 421, Copyright (1988), with permission from Elsevier. It is not covered by the CC-BY 4.0 licence and further reproduction of this panel would need permission from the copyright holder. (B) Schematic shows different regimes of viral behavior dependent on the concentration of a particular drug. At high concentrations (right side of the plot), both drug-resistant (dashed red) and drug-sensitive (solid black) viruses are suppressed, with R₀ below 1. As drug concentration decreases, a window of concentrations emerges where the drug-resistant virus can grow in population size in the presence of the drug ($R_0>1$), but the drug-sensitive genotype cannot. This is termed the ‘mutant selection window’ (Drlica, 2003). At lowest concentrations, both wild-type (WT) and drug-resistant viruses can replicate, but the WT virus out-competes the drug-resistant type because it does not carry the fitness penalty of costly drug resistance mutations. Labels 1 and 2 show how the dynamics of the population in A can be explained by a mutation which behaves like the black arrow in B. If the drug concentration is higher and the resistance mutation only confers a change in R₀ according to the blue arrow, the viral population will remain suppressed.

© 1988, Elsevier

is reprinted with annotations from Figure 1A from Reiss et al., 1988, Copyright (1988), with permission from Elsevier. It is not covered by the CC-BY 4.0 licence and further reproduction of this panel would need permission from the copyright holder.