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.