Circulation of Hepatitis B Virus Variants Carrying Mutations in Polymerase Gene among HBV-Infected and HBV/HIV Coinfected Patients
The aim of the investigation was to study the prevalence of hepatitis B virus (HBV) variants with polymerase gene mutations among HBV-infected and HBV/HIV-coinfected patients previously received no nucleotide/nucleoside analogues therapy.
Materials and Methods. We studied the blood serum samples of 459 patients with HBV-monoinfection and 590 HIV-infected patients (a group with a high risk of HBV infection) who did not receive nucleotide/nucleoside analogues therapy. HBV DNA was determined by PCR method with primers to conservative part of overlapping S and P genes coding the surface protein and DNA-polymerase of HBV, respectively. HBV polymerase gene was sequenced for 241 isolates from HBV-infected patients, and 30 — from patients with HBV/HIV-coinfection. Phylogenic analysis of HBV sequences was performed using Mega 4.0. program.
Results. The viral genome in 7 of 241 patients (2.9%) with HBV-monoinfection was found to have significant amino-acid replacements: in 2 patients (0.8%) — A181S mutation associated with adefovir-resistance, in 4 (1.7%) — T184I related to HBV entecavir-resistance, and in 1 (0.4%) — L199W associated with telbivudine-resistance development. Among 30 examined patients with HBV/HIV-coinfection, 1 patient (3.3%) was found to have significant amino-acid replacement in HBV polymerase gene (in YMDD-motif — M204I) associated with the development of resistance to lamivudine, entecavir, telbivudine and tenofovir. Overall detection rate of primary drug resistance of HBV was 6.2% among HBV-infected and 10% — among HBV/HIV-coinfected patients.
Conclusion. The obtained data on the prevalence of HBV primary drug resistance indicate the need for screening of patients with HBV/HIV-coinfection before starting the antiviral therapy. The patients are to be screened on mutations associated with resistance to the main nucleotide/nucleoside analogues used in hepatitis B therapy.
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