Comparative Effectiveness of Cidofovir Preemptive Therapy for Human Adenovirus Infection in Pediatric Hematopoietic Cell Transplant Recipients. (4th October 2017)

• Record Type: Journal Article
• Authors: Boge, Craig L.K; Petersen, Hans; Seif, Alix E; Cardenas, Ana Maria; Bryan, Matthew; Purdy, Dale; Loudon, Brandon; Kajon, Adriana E; Fisher, Brian T
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S715
• Page End: S715
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.1921
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Human adenovirus (HAdV) has been associated with significant morbidity and mortality in pediatric hematopoietic cell transplant (HCT) populations. This has led some centers to adopt a preemptive approach of plasma surveillance testing with initiation of cidofovir at detection of asymptomatic HAdV. While cidofovir has been shown to have in vitro activity against HAdV there are no comparative effectiveness data for preemptive therapy. Methods: Allogeneic HCT recipients between 2004 and 2013 with asymptomatic HAdV infection detected during plasma surveillance testing within 160 days from transplant were retrospectively identified at Children's Hospital of Philadelphia. A discrete-time failure model was performed to assess the effectiveness of preemptive cidofovir in preventing the progression of HAdV infection. Progression of HAdV infection was defined as a one-log increase in the plasma HAdV viral load or development of HAdV disease within 2 to 21 days of first detection of HAdV in the plasma. HAdV disease was defined by organ-specific radiologic and laboratory data. Inverse probability treatment weights (IPTW) were included in the model to adjust for a patient's likelihood to receive preemptive cidofovir. Results: In 2004–2013, 56 (29.3%) patients developed asymptomatic HAdV infection within 160 days of HAdV infection onset. Thirteen subjects were excluded as they already had progression of HAdV infection within 1 day of plasma detection of HAdV. Of the remaining 43 subjects, 14 (32.6%) had progression of HAdV infection within 21 days of plasma detection. After inclusion of IPTW informed by the absolute lymphocyte count at the time of asymptomatic HAdV infection and number of days from HCT, preemptive cidofovir was associated with a nonsignificant decrease in risk of progression of HAdV infection on any given day (OR: 0.62, 95% CI: 0.13–2.85). Conclusion: Preemptive cidofovir in pediatric HCT recipients with asymptomatic HAdV infection did not result in a statistically significant reduction in the risk of progression of HAdV infection. However, the OR point estimate suggests the possibility for clinical benefit from preemptive therapy. Further investigation with a larger study population is necessary. Disclosures: B. T. Fisher, Pfizer, Inc.: Grant Investigator, Research support. Merck, Inc.: Investigator, Research support. T2 Biosystems, Inc.: Investigator, Research support. Ansun Biopharma: Investigator, Research support