Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression
Figure 8
Dynamic correlation between the rate of HIV-1 evolution and the rate of CD4+ T cell count decline.
(A) Evolutionary rate and CD4+ T-cell level as a function of time relative to seroconversion. Based on the estimation of the evolutionary rate as a function of distance to the root (Figure 1A), the evolutionary rate is plotted as a function of time (average sampled time point of all the sequences within the window). Error bars indicate ±1 standard deviation. The dynamics of the evolutionary rate is linked to that of the CD4+ T-cell count: While the CD4+ T-cell level is stable, the evolutionary rate is stable or increasing; the evolutionary rate starts to decrease when the CD4+ T-cell population is depleted. In patients S-P1 to S-P11, the dashed line indicates the stage when stable CD4+ T-cell count starts to decline. CD4+ T-cell counts were provided by J. Mullins and J. Learn. Red horizontal line denotes the period of antiretroviral therapy for each patient. (B) Correlation between the slope of CD4+ T cell count and the slope of the evolutionary rate (r = 0.68, P = 0.0014). For patients S-P1 to S-P11, the slopes are calculated separately before and after the dashed line. For W-P1 to W-P6, the slopes are measured over the whole range of the data. Note that the slope of the evolutionary rate for W-P6 is very large due to tight sampling, and the slope of the CD4+ T cell count is also high in the corresponding time interval, leading to W-P6 becoming an outlier. The inset shows the average evolutionary rate for different rates of disease progression. Each subject's average evolutionary rate is measured as the ratio between the root distance difference and the sampling time difference, averaged over all the sequence pairs in each tree. The error bars indicate ±1 standard deviation. Because we rooted our trees using a sequence from the initial time point, and not the clade B consensus as done by Wolinsky et al. [22], our calculated evolutionary rate differs from theirs. Subjects S-P2, S-P3, S-P7, S-P9, S-P11, W-P5, and W-P6 were classified as slow disease progressors; S-P1, S-P5, S-P6, S-P7, S-P8, W-P3, and W-P4 as intermediate progessors; and W-P1 and W-P2 as rapid progressors.