Incidence and Clinical Features of Ganciclovir- Resistant Cytomegalovirus Disease in Heart Transplant Recipients

Abstract

The incidence and clinical and virologic aspects of ganciclovir-resistant cytomegalovirus (CMV) disease have not been well-characterized in heart transplant recipients. We retrospectively analyzed all patients who underwent their first heart transplantation during the period from 1 January 1995 through 30 June 2005 at a single health care center. Cox proportional hazard regression was used to assess the relationship between clinical variables and CMV disease. Portions of the UL97 gene were sequenced in patients with slow clinical and/or virologic response to ganciclovir therapy. Cytomegalovirus disease developed in 32 (11.7%) of 274 patients at a median of 4.2 months after transplantation (range, 1.8-11.6 months after transplantation) and was independently associated with donor-seropositive/recipient-seronegative (D+/R-) serostatus (adjusted hazard ratio, 6.93; P<.001). The incidence of ganciclovir-resistant CMV disease was 1.5% overall (4 of 274 patients), 5% among D+/R- serostatus recipients (4 of 80 patients), and 12.5% among patients who developed CMV disease (4 of 32 patients). Ganciclovir-resistant CMV disease was significantly associated with D+/R- serostatus (4 [5%] of 80 vs. 0 [0%] of 153 patients; P=.02), greater prior exposure to ganciclovir (median duration of exposure, 150 vs. 69 days; P=.003), and substantial morbidity, including prolonged CMV-associated hospitalization (median duration of hospitalization, 66 vs. 0 days; P<.01). CMV disease, including ganciclovir-resistant disease, is an important clinical problem in D+/R- heart transplant recipients who receive antiviral prophylaxis. Strategies specifically designed to reduce the incidence and impact of CMV disease in this population are warranted.