Extended Low-Dose Valganciclovir Is Effective Prophylaxis Against Cytomegalovirus in High-Risk Kidney Transplant Recipients With Near-Complete Eradication of Late-Onset Disease

Abstract Background Cytomegalovirus (CMV)-seronegative kidney transplant (KTx) recipients of organs from CMV-seropositive donors (D+/R−) are at increased risk for CMV infection. Despite valganciclovir (VGCV) prophylaxis (900 mg daily for 200 days), late-onset CMV (LO-CMV) occurs at excessive rates....

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Published in:	Transplantation proceedings Vol. 48; no. 6; pp. 2056 - 2064.e1
Main Authors:	Fayek, S.A, Beshears, E, Lieber, R, Alvey, N, Sauer, A, Poirier, J, Hollinger, E.F, Olaitan, O.K, Jensik, S, Geyston, J, Brokhof, M.M, Hodowanec, A.C, Hertl, M, Simon, D.M
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-07-2016
Subjects:	Adult Antiviral Agents - therapeutic use Cytomegalovirus - drug effects Cytomegalovirus Infections - prevention & control Delayed-Action Preparations Drug Resistance, Viral Female Ganciclovir - analogs & derivatives Ganciclovir - therapeutic use Humans Kidney Transplantation - adverse effects Male Middle Aged Postoperative Complications - drug therapy Postoperative Complications - etiology Retrospective Studies Risk Factors Surgery Time Factors Tissue Donors Transplant Recipients
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Summary:	Abstract Background Cytomegalovirus (CMV)-seronegative kidney transplant (KTx) recipients of organs from CMV-seropositive donors (D+/R−) are at increased risk for CMV infection. Despite valganciclovir (VGCV) prophylaxis (900 mg daily for 200 days), late-onset CMV (LO-CMV) occurs at excessive rates. VGCV-associated cost and toxicities remain problematic. Methods We retrospectively evaluated 50 D+/R− adult KTx recipients from August 2008 to August 2014 who received low-dose VGCV (450 mg daily) prophylaxis for an extended duration. The primary outcome was occurrence of CMV disease. Results All patients received depletion induction and underwent ABO-compatible KTx. Mean prophylaxis and follow-up durations were 22.8 and 40.7 months, respectively. Eight patients developed CMV: 5 breakthrough cases (1 case of colitis [2%] and 4 cases of infection [8%]) and 3 cases of LO-CMV (1 syndrome [2.9%] and 2 cases of infection [5.7%]). On logistic regression, longer duration of VGCV prophylaxis was protective against CMV infection or disease ( P = .044; odds ratio, 1.12 [95% confidence interval, 1.03–1.29]). None of 19 recipients with prophylaxis for ≥12 months developed LO-CMV compared with 3 of 16 recipients with prophylaxis for <12 months (18.8%) ( P = .086). Four patients had recurrence of CMV, and 1 patient developed resistance. CMV was not responsible for graft or patient loss and did not affect survival. Conclusions Low-dose VGCV is an effective prophylaxis for D+/R− KTx recipients despite depleting induction. Longer prophylaxis is more protective, and receiving VGCV for ≥12 months nearly eradicated LO-CMV without increasing antiviral resistance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-1345 1873-2623
DOI:	10.1016/j.transproceed.2016.05.004