Assessment of the Human Cytomegalovirus UL97 Gene to identify the Resistance to Ganciclovir in Kidney Transplant Recipients in Labbafi-Nejad Hospital

Abstract

Background: Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation. Approximately, in 60% of the transplant recipients CMV infection can be observed and in > 20% symptomatic diseases can be developed. However, antiviral prophylaxis and treatment have reduced the CMV morbidity and mortality at the time of development of antiviral-resistance CMV strains that can significantly contributed to the adverse clinical outcomes in transplant recipients. Mutations in the human CMV UL97 kinase gene are a major mechanism of viral resistance to the anti-CMV drug “Ganciclovir (GCV)”. GCV, as the most widely used and recognized therapy for CMV, is a substrate for the UL97 kinase. Methods: The studied patients were renal transplant recipients in Tehran Labbafinejad hospital who were positive for CMV-DNA PCR test and have been treated with Ganciclovire. Patients who have been treated for at least 3 weeks with GCV and have not shown a proper therapeutic response were candidate for UL97 gene mutations associated with GCV resistance evaluation. Results: About 60 patients with positive CMV DNA PCR were hospitalized during one year study. Eventually, after 2 times measurement of CMV viral load at the end of the third week and third month of therapy with Ganciclovire, 5 cases were candidate for antiviral resistance evaluation. Genotypic testing was performed, but no mutation neither in UL97 nor in UL 54 was detected by the laboratory. Conclusions: The increasing use of antiviral drugs in transplant patients associated with the narrow range of antiviral agents effective to treat CMV have increased our need for further understanding of the risk factor for development of CMV antiviral resistance and it’s clinical impacts. Detection of UL97 gene mutation plays a major role to determine therapeutic strategies to treat patients infected with the resistant viruses.