Selection of hepatitis B virus (HBV) vaccine escape mutants in HBV-infected and HBV/HIV-coinfected patients failing antiretroviral drugs with anti-HBV activity

Abstract

Background: Given the overlap between envelope and polymerase in the hepatitis B virus (HBV) genome, changes in antigenic sites of the HBV surface antigen may occur as a result of selection of drug-resistance mutations.

Methods: Serum HBV-DNA was isolated from 71 patients with chronic hepatitis B receiving anti-HBV drugs for longer than 12 months, 52 of whom were HIV-positive. The reverse transcriptase/envelope gene from each HBV isolate was amplified using a nested polymerase chain reaction (PCR) covering 720 bp (aa 48 to 288), which includes all known nucleos(t)ide analogue resistance mutations in HBV.

Results: All but 13 patients had received lamivudine. Of the rest, 10 HBV-monoinfected subjects had received adefovir and 3 HBV/HIV-coinfected patients had been treated with tenofovir. Only lamivudine-resistance-associated mutations produced changes in the HBV envelope antigenic sites. Lamivudine resistance mutations were more frequent in HBV genotype A than D (P = 0.014). Contrary to monoinfected individuals, HBV genotype A was the predominant genotype among HBV/HIV-coinfected patients. The triple-HBV mutant rtV173L + rtL180M + rtM204V, which has been shown to produce a diminished hepatitis B surface (HBs) antigen-antibody binding, was found in 3 individuals, all coinfected with HIV and HBV.

Conclusion: Circulation of HBV encoding envelope mutations with diminished HBs antigen-antibody binding as result of selection of drug-resistance mutations may occur, particularly in patients infected with HBV genotype A, the most prevalent genotype among HBV/HIV-coinfected patients. Such mutations might represent a public health concern because of the potential risk of transmission of HBV drug- and vaccine-resistant strains.