High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

BACKGROUND AND AIMS: Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations. METHODS: This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger’s sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool. RESULTS: Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18). CONCLUSIONS: The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.