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Impact of High‐Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients
Author(s) -
Siodlak Magdalena,
Jorgenson Margaret R.,
Descourouez Jillian L.,
Leverson Glen E.,
Mandelbrot Didier A.,
Smith Jeannina A.,
Redfield Robert R.
Publication year - 2018
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2126
Subject(s) - medicine , valganciclovir , interquartile range , ganciclovir , immunosuppression , gastroenterology , retrospective cohort study , cytomegalovirus , population , surgery , human cytomegalovirus , immunology , viral disease , herpesviridae , virus , environmental health
Study Objective To evaluate the clinical course and long‐term impact of high‐dose acyclovir ( HD ‐A, 800 mg 4 times/day) cytomegalovirus ( CMV ) prophylaxis failure in a CMV ‐seropositive abdominal solid organ transplant population. Design Retrospective cohort study. Setting Tertiary academic medical center. Patients A total of 691 adults who received solid organ transplants between January 1, 2008, and June 30, 2013, without lymphocyte‐depleting induction and were prescribed 3 months of HD ‐A prophylaxis at the time of hospital discharge. Of those patients, 54 experienced prophylaxis failure, defined as CMV detected via molecular diagnostics or on biopsy while receiving HD ‐A (prophylaxis failure group), and 637 did not (comparator group). Measurements and Main Results Mean ± SD time to failure was 64 ± 23 days; 98% (53/54 patients) was attributable to viremia diagnosed via positive polymerase chain reaction ( PCR ). Of these 53 patients, 34% (18 patients) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 1531 IU/ml (interquartile range [ IQR ] less than 250–2947) and 4442 IU/ml ( IQR less than 250–32,500); 19 (36%) had a single detectable CMV PCR . Treatment was required in 56% (30/54 patients), with a median duration of 63 days; 40% (12 patients) were treated with valganciclovir alone, and the remainder received intravenous ganciclovir. CMV disease resulted in hospitalization in 28% (15 patients). Immunosuppression was modified in 52% (28 patients). The rate of CMV recurrence after 100 days was significantly higher in the prophylaxis failure group (59% vs 13%, p<0.0001). Higher rates of rejection; higher rates of 1‐, 3‐, and 5‐year graft failure; and higher rates of 1‐, 3‐, and 5‐year mortality were noted in the prophylaxis failure group on univariate analysis (43% vs 30%, p=0.045; 8%, 17%, and 34% vs 4%, 12%, and 17%, p=0.006; and 6%, 17%, and 26% vs 1%, 6%, and 10%, p=0.003, respectively). Multivariate analysis demonstrated an increased risk of graft failure in the prophylaxis failure group (hazard ratio [ HR ] 1.76, 95% confidence interval [ CI ] 1–3.1, p=0.0499) and a trend to increased mortality ( HR 1.6, 95% CI 0.83–3.1, p=0.16). Conclusion Prophylaxis failure with HD ‐A was mostly limited to mild viremia; however, it was associated with significantly reduced long‐term graft survival, likely reflecting the negative impact of CMV viremia.