Drug-Resistant Mutations in 3 Pediatric Cases of Chronic Hepatitis B Following Lamivudine Therapy

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Abstract
Managing chronic hepatitis B in children presents significant challenges, particularly due to the risk of antiviral resistance with prolonged lamivudine use. We report 3 pediatric cases in Vietnam who experienced virologic breakthrough after lamivudine therapy failure. Genotypic testing of the hepatitis B virus polymerase gene revealed resistance mutations: M204V/I in all 3 cases, L180M in 2 cases (cases 2 and 3), L80I in case 1, and M250L in case 2. After resistance was identified, switching to tenofovir disoproxil fumarate achieved complete viral suppression, whereas switching to entecavir resulted in a partial yet clinically meaningful virologic response, due to cross-resistance conferred by the M204V/I mutations. These cases provide clinical observations from a resource-limited setting, suggesting that tenofovir disoproxil fumarate may be preferable to entecavir for salvage therapy following lamivudine failure. This emphasizes the urgent need for accessible genotypic testing to guide treatment decisions and prevent the use of ineffective sequential monotherapies.