ObjectivesWe conducted this study to describe whether mutations in the gene coding for the enzyme reverse transcriptase (RT) were related to drugs used in the treatment of hepatitis B in Vietnam. MethodsPatients receiving antiretroviral therapy with evidence of treatment failure were included in the study. The RT fragment was cloned using the polymerase chain reaction technique after being extracted from patients’ blood samples. The nucleotide sequences were analysed using Sanger method. The HBV drug resistance database contains mutations associated to resistance to existing HBV therapies. Medical records were accessed to collect information on patient parameters, such as treatment, viral load, biochemistry, and blood count. ResultsResistance mutations to lamivudine, telbivudine, and entecavir were found in the highest proportion (75–91.7%) of HBV samples from patients who had failed antiretroviral therapy. Only 20.8% of HBV strains had mutations exhibiting adefovir resistance, while none had mutations conferring tenofovir resistance. M204I/V, L180M, and L80I are frequent variants linked with resistance to lamivudine, telbivudine, and entecavir. In contrast, the A181L/T/V mutation was detected predominantly in tenofovir-resistant HBV strains. Following the drug resistance mutation test, patients achieved the greatest virological response after 24 weeks of therapy with tenofovir and entecavir at a daily dose of one tablet. ConclusionLamivudine, telbivudine, and entecavir were all highly resistant to the RT enzyme modifications in 24 treatment failure patients, with M204I/V, L180M, and L80I being the most prevalent mutations. Tenofovir resistance mutations have not been found in Vietnam.