A patient on antiretroviral therapy has a viral load of 25,000 copies/mL after 6 months despite reported adherence. Genotypic resistance testing shows a M184V mutation in the reverse transcriptase gene. Which drug has this mutation primarily arisen against?
- A Lamivudine (3TC) or Emtricitabine (FTC) ✓
- B Tenofovir disoproxil fumarate (TDF)
- C Efavirenz (NNRTI)
- D Zidovudine (AZT)
Explanation
The M184V (methionine to valine substitution at codon 184 of reverse transcriptase) is the signature resistance mutation for lamivudine (3TC) and emtricitabine (FTC), both nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) that are thymidine analogue-independent. M184V paradoxically improves sensitivity to tenofovir and partially restores it to zidovudine. NNRTI resistance involves different mutations (K103N, Y181C for efavirenz). Zidovudine resistance is associated with thymidine analogue mutations (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219Q).
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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