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

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.

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.

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).

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.

All authors: No reported disclosures.