Figure 2.
Figure 2. Kinetics of adenoviremia in 12 patients treated with cidofovir followed by brincidofovir. (A) Kinetics of adenoviremia (plotted on left y-axis) and corresponding lymphocyte count (plotted on right y-axis) in 12 episodes treated with cidofovir followed by brincidofovir. Days after HCT are plotted on x-axis. Black arrows indicate the start of cidofovir and blue arrows indicate the start of brincidofovir. Major (blue line) and minor (broken blue line) responses were observed in 9 of 11 episodes unresponsive to cidofovir. No response in 2 weeks is shown as red line. The circulating lymphocyte count is shown as brown line and CD4+ T-cell count (where available) is shown as green diamonds. The median circulating lymphocyte count at CR was 300/μL (160 to 3000). In patient number 10, coexistent CMV viremia (broken green line) resulted in T-cell expansion and resolution of CMV viremia. However, adenoviremia and gut adenoviral disease continued despite CD4+ T-cell reconstitution. Adenovirus-specific T-cell response was absent despite CD4+ T-cell expansion (shown as green circle). In the remaining 7 patients who had lymphocyte subsets measured, CD4+ T cells were <100/μL. (B) Change in adenovirus load between cidofovir and brincidofovir in patients unresponsive to cidofovir (n = 11). The median change in log10 viral load on cidofovir treatment was +1.2 (range, 0.3 to 2.3). In contrast, median change in log10 viral load after 2 weeks of brincidofovir treatment was −2.9 (range, −5.1 to 0.6; P < .005). The solid lines represent median and IQR, and whiskers represent minimum and maximum values. Pt, patient.

Kinetics of adenoviremia in 12 patients treated with cidofovir followed by brincidofovir. (A) Kinetics of adenoviremia (plotted on left y-axis) and corresponding lymphocyte count (plotted on right y-axis) in 12 episodes treated with cidofovir followed by brincidofovir. Days after HCT are plotted on x-axis. Black arrows indicate the start of cidofovir and blue arrows indicate the start of brincidofovir. Major (blue line) and minor (broken blue line) responses were observed in 9 of 11 episodes unresponsive to cidofovir. No response in 2 weeks is shown as red line. The circulating lymphocyte count is shown as brown line and CD4+ T-cell count (where available) is shown as green diamonds. The median circulating lymphocyte count at CR was 300/μL (160 to 3000). In patient number 10, coexistent CMV viremia (broken green line) resulted in T-cell expansion and resolution of CMV viremia. However, adenoviremia and gut adenoviral disease continued despite CD4+ T-cell reconstitution. Adenovirus-specific T-cell response was absent despite CD4+ T-cell expansion (shown as green circle). In the remaining 7 patients who had lymphocyte subsets measured, CD4+ T cells were <100/μL. (B) Change in adenovirus load between cidofovir and brincidofovir in patients unresponsive to cidofovir (n = 11). The median change in log10 viral load on cidofovir treatment was +1.2 (range, 0.3 to 2.3). In contrast, median change in log10 viral load after 2 weeks of brincidofovir treatment was −2.9 (range, −5.1 to 0.6; P < .005). The solid lines represent median and IQR, and whiskers represent minimum and maximum values. Pt, patient.

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