Hepatitis B virus variants with natural resistance to adefovir and lamivudine and S-escape mutants isolated from children in Argentina.

CUESTAS ML, .; MATHET VL,; MINASSIAN ML,; TRINKS J,; RIVERO C,; ANDREETTA AM,; CASTILLO A,; GENTILE E,; LEZAMA C,; GALOPPO M,; GIACOVO G,; GALOPPO C,; OUBIÑA JR

Buenos Aires

Congreso; . 6th World Congress of the World Society for Pediatric Infectious Diseases; 2009

World Society for Pediatric Infectious Diseases

Background and aims: Despite the availability of therapeutic and preventive strategies, Hepatitis B virus (HBV) infection is still the most common cause of liver cirrhosis and hepatocellular carcinoma. The unique genomic structure and the replication cycle of HBV together with the high error-prone of its viral polymerase provide much opportunity for mutations to occur. Emergence of different viral variants or “escape” mutants is thus inevitable. In this connection, several reports have documented the appearance of S-escape mutants from protective anti-HBs antibodies, the occurrence of drug-resistant mutants to the current nucleos(t)ide analogues approved for the treatment of chronic hepatitis B; and the presence of pre-core/core and X mutants that may cause severe and progressive liver disease. The aim of this study is to report three cases of chronically HBV-infected children in Argentina who developed natural antiviral resistance to adefovir, and one of them to lamivudine as well. Two of the patients studied are also carriers of S-escape mutants. Methods. Serum samples from 3 chronically infected HBV pediatric patients who had never undergone antiviral therapy were the source of viral DNA. PCR-amplification and sequence analysis of the overlapping S/Pol genes were carried out. Results. This study reports 3 cases of chronically HBV-infected patients, who developed natural resistance to adefovir (rtL217R), and one of them to lamivudine as well (rtL180M+M204V). Two of these patients were also carriers of S-mutants (Y100C, P120L, T125S, P127C, D144A and Y161F). . Conclusion. Sequence analysis of the HBV reverse transcriptase should be an essential tool before starting an antiviral regimen. Circulation and transmission of S-escape variants resistant to antiviral drugs should be of public health concern as they may represent a potential risk for the community.