1747. Impact of Inappropriately Low Cytomegalovirus (CMV) Prophylaxis Dosing on CMV Outcomes Among Lung Transplant (LT) Recipients

Abstract Background Valganciclovir (VGCV) and ganciclovir (GCV) are commonly used to prevent CMV in at-risk lung transplant recipients (LTRs). Because renal function changes frequently in the post-transplant setting, antiviral under-dosing may occur. We sought to determine the frequency of GCV/VGCV under-dosing and its impact on CMV-related outcomes among LTRs. Methods We conducted a retrospective cohort study of all adult LTRs with a CMV seropositive donor (D+) between 2014 and 2016 at the Hospital of the University of Pennsylvania. Exposed patients were those with exposure to inappropriately low-dose GCV/VGCV. Unexposed patients were those whose antiviral dosing was consistently appropriate for their creatinine clearance. We employed a multivariable Cox proportional hazard analysis to determine the impact of low-dose prophylaxis on time to CMV infection post-transplant; prophylaxis dosing was incorporated as a time-varying covariate in this survival analysis. Results 108 adults underwent CMV D+ LT during the study period. 46 (43%) experienced low prophylaxis dosing at some point during their prophylaxis course. 47 (43%) LTRs developed CMV viremia, of which 10 (9%) were still on prophylaxis. 20 (19%) LTRs developed CMV disease and 6 (6%) had ganciclovir-resistant CMV. In the multivariable Cox analysis, we found that there was not a significant association between exposure to any low-dose prophylaxis and the hazard of CMV infection (HR = 1.001, 95% CI 0.99–1.01, P = 0.75; Table 1), even among CMV seronegative recipients (D+/R−) (HR = 1.002, 95% CI 0.99–1.01, P = 0.68). When only those who received > 28 days of low-dose prophylaxis (N = 6, 6%) were evaluated, there was a trend toward an increased hazard of CMV infection (HR = 1.001, 95% CI 0.999–1.004, P = 0.18; Table 2). Conclusion CMV D+ LTR are frequently exposed to inappropriately low CMV prophylaxis dosing. This does not appear to significantly increase the risk for CMV infection, though prolonged subtherapeutic exposure merits further exploration as a risk factor for CMV outcomes in higher-risk patients. Disclosures All authors: No reported disclosures.