Lamivudine therapy for chronic hepatitis B frequently fails after one to two years because resistance appears rapidly. Resistance maps to which feature of the hepatitis B virus?
- A Mutations in the YMDD motif of the reverse transcriptase domain of the viral polymerase ✓
- B Mutations in the surface antigen 'a' determinant escaping neutralization
- C Mutations in the basal core promoter increasing X gene transcription
- D Mutations in the packaging signal epsilon allowing encapsidation escape
Correct answer: A. Mutations in the YMDD motif of the reverse transcriptase domain of the viral polymerase
Explanation
HBV replicates through an RNA intermediate, so its polymerase functions as a reverse transcriptase, and nucleos(t)ide analogues act on this RT domain. Lamivudine resistance arises from mutations in the conserved YMDD (tyrosine-methionine-aspartate-aspartate) catalytic motif of the RT region, analogous to HIV resistance. The 'a' determinant mutations produce HBsAg vaccine/diagnostic escape, and precore or basal core promoter changes alter HBeAg expression, not drug susceptibility, eliminating the remaining distractors.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.