Association between adenovirus viral load and mortality in pediatric allo-HCT recipients: the multinational AdVance study

This multivariable analysis from the AdVance multicenter observational study assessed adenovirus (AdV) viremia peak, duration, and overall AdV viral burden-measured as time-averaged area under the viremia curve over 16 weeks (AAUC(0-16)) -as predictors of all-cause mortality in pediatric allo-HCT recipients with AdV viremia. In the 6 months following allo-HCT, 241 patients had AdV viremia >= 1000 copies/ml. Among these, 18% (43/241) died within 6 months of first AdV >= 1000 copies/ml. Measures of AdV viral peak, duration, and overall burden of infection consistently correlate with all-cause mortality. In multivariable analyses, controlling for lymphocyte recovery, patients with AdV AAUC(0-16) in the highest quartile had a hazard ratio of 11.1 versus the lowest quartile (confidence interval 5.3-23.6); for peak AdV viremia, the hazard ratio was 2.2 for the highest versus lowest quartile. Both the peak level and duration of AdV viremia were correlated with short-term mortality, independent of other known risk factors for AdV-related mortality, such as lymphocyte recovery. AdV AAUC(0-16), which assesses both peak and duration of AdV viremia, is highly correlated with mortality under the current standard of care. New therapeutic agents that decrease AdV AAUC(0-16) have the potential of reducing mortality in this at-risk patient population.