Evolution of Drug-Resistant Viral Populations during Interruption of Antiretroviral Therapy▿†
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Fig. 1.Detection of the M184V mutation after treatment interruption. The M184V mutation was determined by PASS in plasma samples collected on therapy (week −10) and off therapy (week 3 to week 32) in patient PID811. Green and red dots indicate mutant and WT bases detected in amplified individual viral genomes, respectively. Viral loads (VL), numbers of viral genomes detected, numbers of mutants in the viral population, and percentages of mutant viruses in the sequenced genomes are shown above and underneath the PASS images. Due to limited sampling of the viral population, the percentages of mutants observed may differ from the percentage of mutants in the population (see Materials and Methods).
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Fig. 2.Evolution of drug resistance mutations following treatment interruption. Detected individual drug resistance mutations were plotted as percentages (A, C, E, and G) and absolute numbers (B, D, F, and H) in the viral population at each time point in each individual. Drug resistance mutations are indicated by unique symbols as shown at the far right for each patient. The RTI mutations are shown as solid lines, and the PI mutations are shown as dotted lines. The WT virus and viral load data are indicated as red triangles and black crosses, respectively. WT viruses were not included in patient PID895 in order to show the differences among minority drug-resistant virus populations (G and H). The G48V mutation was not analyzed at week 11 and is not shown in the plots (C and D).
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Fig. 3.Dynamic changes of linked MDR viruses following treatment interruption. The viral population changes over time were compared in patients PID811 (A), PID908 (B), and PID268 (C). The numbers of linked drug resistance mutations in viruses are indicated by different symbols and colors as indicated in each graph. The population changes of select predominant viruses with linked MDR mutations in patient PID811 were compared (D).
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Fig. 4.Relationship between relative fitness loss of drug resistance mutants compared to the WT virus and the numbers of drug resistance mutations. The vertical bars indicate the 95% confidence interval range. Note that for patient PID268, the error bars are so small that they cannot be easily visualized. The dashed lines represent the best fit for the trend of fitness loss with higher numbers of mutations.
- Copyright © 2011, American Society for Microbiology
