Purpose: Evaluate the incidence of cytomegalovirus (CMV) infection in seropositive (R+) solid organ transplant recipients (SOT) receiving high-dose acyclovir (HD-A, 800 mg QID) prophylaxis.

Methods: Retrospective single-center study of R+ adult SOT transplanted without lymphocyte-depleting induction between 1/1/2000-6/30/2013 prescribed 3 months of HD-A prophylaxis at time of hospital discharge. Primary outcome was incidence of prophylaxis failure overall, defined as any CMV infection during the prophylactic period. Secondary outcomes included overall incidence of biopsy-proven tissue invasive disease (TIDx) and subgroup analyses by allograft type.

Results: A total of 1525 transplant recipients met inclusion criteria: 944 renal (RTX), 108 simultaneous pancreas-kidney (SPK), 462 liver (LTX), and 11 pancreas (PTA). During the prophylactic period overall rate of prophylaxis failure was 7% and overall rate of TIDx was 0.4%. On subgroup analysis rate of failure in the RTX population was 4.5% overall with 0.2% incidence of TIDx, SPK – 6.1% overall with no TIDx, LTX -11% overall with 0.7% TIDx and PTA – 20% overall with 10% TIDx. Failure occurred at a statistically significantly higher rate in the LTX population then the RTX population (p=<0.0001, HR 2.6), Incidence of TIDx was minimal and not significantly different between groups (p=0.34). In order to elucidate risk factors associated with failure in the population most likely to benefit from alternative prophylactic schemes (LTX) a multivariable analysis was conducted. CMV donor negativity was associated with a decreased risk of failure (p<0.0001, HR 0.176). Mechanical ventilation increased risk of failure by 1.05 for each week received post-operatively (p=0.04).

Conclusions: In this single center cohort there was a measurable incidence of CMV infection during the 3 month prophylactic period with HD-A. Breakthrough CMV appears to be limited to viremia. In the LTX subgroup donor seronegativity had a protective effect against failure while increasing ventilation time increased risk. Overall, HD-A does not appear to be an appropriate prophylactic modality; however investigation of its use in recipients of CMV seronegative liver allografts is warranted due to known tolerance issues with the standard of care in this population.

CITATION INFORMATION: Fose J, McCreary E, Jorgenson M, Lucey M, Smith J. High-Dose Acyclovir for Cytomegalovirus Prevention in Seropositive Solid Organ Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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