Purpose: To describe the long-term clinical impact of high-dose acyclovir (HD-A, 800 mg 4 times daily) cytomegalovirus (CMV) prophylaxis failure in the seropositive (R+) abdominal solid-organ transplant (aSOT) population

Methods: Retrospective single-center study of R+ adults who received aSOT without lymphocyte-depleting induction between 1/1/2008-6/30/2013 prescribed 3 months of HD-A prophylaxis at the time of hospital discharge. Primary goal was to describe cases of patients who experienced prophylaxis failure defined as CMV detected via molecular diagnostics or on biopsy while receiving HD-A. Secondary outcomes included evaluation of long-term impact of prophylaxis failure including recurrent viremia, rejection, graft loss, and mortality.

Results: A total of 691 patients met inclusion criteria; 54 in the breakthrough group, and 637 in the comparator (Table 1). Mean time to prophylaxis failure in the breakthrough group was 64 ± 23 days. Failure attributed to viremia diagnosed via positive polymerase-chain reaction (PCR) accounted for 98% (n=53) of patients with breakthrough disease; of these 33% (n=18) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 2633 copies/ml and 7641 copies/ml; 35% had a single detectable CMV PCR. Treatment was required in 56% who experienced failure. Median duration of treatment was 63 days; 43% were treated with valganciclovir alone, the remainder received intravenous ganciclovir. Only 28% required hospitalization for CMV disease; however 54% were already inpatient at detection of viremia. Baseline immunosuppression was modified in 52%. In the breakthrough group 58% went on to have CMV disease >100 days after transplant vs 17% in the comparator group (p<0.0001). Rejection occurred in 43% of the breakthrough group vs 30% in the comparator group (p=0.045). Overall rates of graft loss were 92%, 83%, 66% in the breakthrough group vs 96%, 88%, 83% in the comparator (p=0.006); 1,3 and 5 years mortality was 94%, 83%, 74% vs 99%, 94%, 90% (p=0.003).

Conclusion: In this observational study prophylaxis failure while receiving HD-A was mostly limited to mild viremia, however the breakthrough group had significantly worse long term graft and patient survival, perhaps reflecting the negative impact of the presence of CMV viremia.

CITATION INFORMATION: Fose J., Jorgenson M., Siodlak M., Leverson G., Smith J., Redfield R. Impact of High Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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