1469. Drug-resistance associated mutations of Human Cytomegalovirus (CMV) UL97 and UL54 genes in immunocompromised patients. Experience in Colombia, South America.

Abstract

Abstract Background Cytomegalovirus (CMV) infection is a significant disease in immunocompromised patients, particularly transplant patients. The wide use of antivirals for prophylaxis and treatment has decreased the incidence and impact of this disease. Although, this exposure can lead to mutations in CMV UL54 and UL97 genes, which are associated with antiviral resistance. Little is known of the frequency of these mutations in Latin America, despite an increase in the transplant population. Methods We performed a prospective observational study. Patients with suspected CMV resistance based on the persistence of CMV DNAemia despite treatment were included from April to December 2019 in Fundación Valle del Lili. The blood samples were processed for DNA extraction, amplification, and sequencing for molecular characterization of (UL97) and (UL54) genes. Laboratory and clinical data were recollected from the clinical laboratory database and clinical charts. Results We enrolled 50 patients with CMV DNAemia, 32 amplified for gene sequencing. The median age was 31.7 years old, and 46.8% were males. 65.6% had a stem cell transplant, and 28.1% had a solid organ transplant. Only 65.2% had previous antiviral exposure. 93.7% manifested with CMV DNAemia alone, and 6.2% had CMV disease, hepatitis, and colitis. According to our findings, 56.2% had only UL54 mutations, 6.25% had only UL97 mutations, and 37.5% had both. The mutations associated with antiviral resistance were D605E and A594V for UL97 and A692S for UL54. The most common UL97 polymorphisms were V355A and F396L, while for UL54 were N898D, N685S, and S655L. On day 14 of treatment, 21.8% (7/32) had treatment failure. No canonic resistance mutations were found. 15.6% (5/32) of patients died; none had UL97 mutations, two had UL54 mutations associated with antiviral resistance, and three had polymorphisms of this gene. Conclusion Our study is the first one performed in Colombia. Although resistance was low, it was present in a few patients and related to mortality. It is important to study this evolving resistance as the use of antivirals increases in the transplant population in Latin America. Disclosures Olga Agudelo, n/a, Fundación valle del lili: Board Member.