Antiviral drug-associated potential vaccine-escape hepatitis B virus mutants in Turkish patients with chronic hepatitis B

Abstract

The hepatitis B virus (HBV) polymerase (pol) gene completely overlaps with the envelope (S) gene. Mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in the overlapping hepatitis B surface antigen (HBsAg). Recent studies have conferred a new acronym to these HBV pol/S gene overlap mutants: ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The present study aimed to assess the prevalence and pattern of ADAPVEMs in Turkish patients with chronic hepatitis B (CHB). The investigation was conducted between March 2007 and July 2010 and involved a total of 442 patients. These patients were in the following phases of HBV infection: immune tolerant (n=50), immune reactive (n=37), inactive carrier (n=90), HBeAg-negative CHB (n=217), and HBsAg-negative (n=12), or were hemodialysis patients (n=36). One hundred eighty-six patients were receiving nucleos(t)ide analogue (NUC) therapy and 256 patients had treatment-naïve CHB. Seven types of ADAPVEM were detected in the total CHB patients: rtM204V/sI195M, rtM204I/sW196S, rtM204I/sW196L, rtV173L/sE164D, rtA181T/sW172*, rtA181T/sW172L, and rtA181V/sL173F. The ADAPVEMs were associated with lamivudine, telbivudine, and adefovir. The prevalence of ADAPVEMs in all CHB patients was found to be 10% (46/442). The difference in the prevalence of ADAPVEMs across the different CHB clinical phases was not significant (Pearson Chi-square, p=0.112). The prevalence of ADAPVEMs was 24% (44/186) in those undergoing NUC therapy and 0.7% (2/256) in the treatment-naïve group; this difference was significant (Pearson Chi-square, p=0.00). We determined the prevalence and pattern of ADAPVEMs in Turkish patients in the different phases of CHB. Preferred drugs in Turkey, such as lamivudine, have the potential to cause the emergence of ADAPVEMs, with the possibility that these will spread to both individuals immunized with the hepatitis B vaccine and nonimmunized individuals. ADAPVEMs should be monitored in infected and treated patients and their public health risks assessed.