Prolonged Low-Dose Prophylaxis With Valganciclovir in Cytomegalovirus-Negative Recipients of Kidney Transplants From Cytomegalovirus-Positive Donors Allows Seroconversion and Prevents Cytomegalovirus Disease

• Published in: Transplantation proceedings 2017-12, Vol.49 (10), p.2280-2284
• Main Authors: Halleck, F., Khadzhynov, D., Schrezenmeier, E., Lehner, L., Budde, K., Staeck, O.
• Format: Article
• Language: English
• Subjects: Adult; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Cytomegalovirus - drug effects; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - transmission; Cytomegalovirus Infections - virology; Drug Administration Schedule; Female; Ganciclovir - administration & dosage; Ganciclovir - analogs & derivatives; Humans; Incidence; Kidney Transplantation - adverse effects; Longitudinal Studies; Male; Middle Aged; Postoperative Complications - prevention & control; Postoperative Complications - virology; Pre-Exposure Prophylaxis - methods; Retrospective Studies; Seroconversion - drug effects; Time Factors; Tissue Donors; Transplants - immunology; Transplants - virology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2017.10.004

Cytomegalovirus-negative recipients of kidneys from cytomegalovirus (CMV)-positive donors (D+/R−) are at high risk to develop severe clinical manifestations of CMV disease. Long-term data about incidence and timing of CMV seroconversion, CMV disease, and the influence of prolonged valganciclovir prophylaxis on the clinical course of CMV infection are missing. We conducted a retrospective long-term study of 89 consecutive CMV D+/R− kidney transplant recipients transplanted between 2003 and 2012. All recipients received valganciclovir prophylaxis after transplantation (median 187 [126-261] days) with a median dose of 213 (181-338) mg/d. Long-term outcome was assessed over a maximum of 10 years post-transplant. During follow-up (median 62 months) 60 of 89 (67%) patients had CMV seroconversion, and 29 of 89 (33%) developed symptomatic CMV disease. In addition, in 38 of the 60 (63%), seroconversion occurred during prophylaxis (median 154 days post-transplant), and in 22 patients, after the end of prophylaxis (median 320 days after transplantation). Baseline characteristics of the 2 groups did not differ significantly. Seroconversion during prophylaxis vs seroconversion after the end of prophylaxis was associated with significantly lower incidence of CMV disease (34% vs 73%, P = .007), less severe CMV disease (16% vs 64%, P < .001), and fewer organ manifestations (26% vs 64%, P = .006). The risk of CMV disease was limited to the first 475 days after transplantation. Valganciclovir resistance occurred in just 1 case (1%). Prolonged prophylaxis with low-dose valganciclovir allowed CMV seroconversion during prophylaxis in a high proportion of D+/R− patients. Seroconversion occurred after a median of 154 days and was associated with significantly lower incidence of CMV disease, less severe CMV disease, and fewer CMV complications.