Figure 3

Effect of immune pressure on rate of development and reversion of drug resistance. (a) Concentration of digestive (C _d ), plasma (C _b ), intracellular (C _c ), intracellular phosphorylated (C _cp ), and intracellular diphosphorylated (C _cpp ) tenofovir using the model of Dixit and Perelson [42] that includes drug partitioning across the cell membrane. (b) Example of viral load and CD4+ T cell response to TDF monotherapy with perfect adherence and cessation after 300 days. TDF-DP concentration, re-scaled from (a) in units of μg/mL along the righthand axis, is overlaid for reference. (c) Basic reproductive ratio of WT and drug-resistant virus at steady-state peak and trough TDF-DP concentrations, as a function CTL efficacy p varied with f to maintain a setpoint viral load of 51,000 copies/mL. (d) Influence of p, varied as in (c), on the time from HIV infection on TDF monotherapy until emergence of the K65R mutant at a viral load above 50 copies/mL. The time to resistance is 29 days at p = 0, and rises to ever-increasing durations as p reduces R₀. (d) Influence of p on the time until reversion of resistance after monotherapy cessation. Reversion times range from 37 days at p = 0 to 15 days as R₀ approaches 1.