We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R-patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigatortreated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p = 0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, oncedaily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.

We investigated the emergence of cytomegalovirus (CMV) ganciclovir-resistance mutations in 301 high-risk solid-organ transplant (SOT) recipients after oral prophylaxis, for 100 days, with either valganciclovir or ganciclovir. For patients treated with ganciclovir, the incidence of CMV UL97 mutations was 1.9% (2/103) at the end of prophylaxis and 6.1% (2/33) for patients with suspected CMV disease up to 1 year after transplantation. No resistance mutations were detected in samples from valganciclovir-treated patients. Dual polymerase (UL54) and UL97 resistance mutations were not seen. Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients.

The frequency of constipation and diarrhoea remains relatively stable over time. Changes in IBS subtypes are common, but changes between constipation and diarrhoea are rare. Alternating IBS is more frequent in women.

Despite prophylaxis, cytomegalovirus (CMV) disease is common in donor seropositive (D+ +)/recipient seronegative (R-) transplant patients after cessation of prophylaxis. Early detection of CMV may allow for preemptive therapy to prevent active disease. The clinical utility of quantitative plasma viral load measurements for predicting CMV disease was determined in 364 D+ +/R-organ transplant patients receiving prophylaxis (100 d of valganciclovir or oral ganciclovir). Measurements were performed every 2 weeks until day 100 and at months 4, 4.5, 5, 6, 8 and 12 post-transplant. CMV disease occurred in 64 (17.6%) patients by 12 months. Using a positive cut-off value of > > 400 copies/mL, sensitivity was 38%, specificity 60%, positive predictive value 17%, and negative predictive value 82% for prediction of CMV disease. Therefore, routine monitoring would have predicted disease in only 24/64 (38%) patients. The test characteristics were not improved by changing the viral load cut-off point for defining a positive result. Similarly, single time point measures at the end of prophylaxis or month 4 had low sensitivity for disease prediction. Overall, regular CMV plasma viral load measurements were only of modest value in predicting CMV disease.

Low Ccr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC- and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.