Primer ve Sekonder İmmün Yetmezlikli Hastalarda Saptanan Sitomegalovirüs Suşlarında Gansiklovir Direncinin Genotipik Yöntemlerle Araştırılması

Abstract

Firtina A, Investigation of ganciclovir resistance in cytomegalovirus strains isolated from patients with primary and secondary immunodeficiency by genotypic methods, Hacettepe University, Faculty of Medicine, Department of Medical Microbiology, Thesis In Medical Microbiology, Ankara, 2023. Patient groups with immunodeficiency are increasing with the advancement of modern medicine. CMV causes serious illness and death as an opportunistic pathogen, especially in immunocompromised patient groups such as transplant patients and individuals living with HIV. Sometimes, these infections do not respond clinically to ganciclovir, the first-line treatment option. As a result, prolonged treatment and hospitalization time, medical treatment changes with more side effects, permanent organ damage and processes that can lead to death may occur. Considering all these, the importance of antiviral resistance tests in the treatment process increases even more. In this study, it was aimed to investigate CMV infections in patients with primary and secondary immunodeficiency admitted to Hacettepe hospitals and the presence of resistance to ganciclovir in CMV strains causing this infection by genotypic methods. It has been hypothesized that patients with CMV organ involvement have more antiviral resistance than those without. Plasma from patients included in the study for one year were prospectively collected. CMV DNA isolation was performed from plasma samples of 142 patients in total. After primer design and nested-PCR optimization, all DNA isolates were included in this PCR experiment. As a result of the experiments, bands were detected in the targeted region in 77 patients. Band-detected sequences were sequenced by the Sanger DNA sequencing method, resulting in data for 77 patients. The resulting sequences were interpreted on a readily available resistance-associated mutation detection platform. As a result, M460V and A594V mutations associated with ganciclovir resistance were detected in two of 77 patients. D605E mutation associated with genetic polymorphism was found in two patients. In addition, the V542I mutation with unknown effect on ganciclovir resistance was shown in three patients, and the presence of A435V and A427T mutations in two separate patients. Thirty two patients were hematopoietic stem cell transplant (HSCT) recipients, and three patients had possible lung involvement and one patient had CMV pneumonia. The patient diagnosed with CMV pneumonia was the patient with the A594V mutation. In this group, GIS involvement was observed in two patients and retinitis was observed in four patients. The M460V mutation was observed in the patient who was treated with the diagnosis of CMV retinitis. Except for the lung involvement seen in one HIV patient, all organ involvements were seen in HSCT recipients. In addition, seven solid organ transplant (SOT), three HIV infection, two congenital CMV infection and 33 patients with immunodeficiency due to other diseases participated in our study. Possible CNS involvement was observed in one of the patients with congenital CMV infection. In conclusion, no significant difference was found between the patient groups with and without CMV organ involvement in terms of ganciclovir resistance. It was concluded that there is a need for studies that increase the number of participants in patient groups and evaluate each patient group individually.