Sanger sequencing of the HIV-1 reverse transcriptase gene from a treatment-naive patient reveals an M184V mutation. Which antiretroviral drug is this mutation most commonly associated with, and what is its clinical implication?

• A Lamivudine/Emtricitabine — confers high-level resistance but hypersensitises the virus to zidovudine ✓
• B Efavirenz — associated with K103N and V179D mutations, not M184V
• C Tenofovir alafenamide — K65R is the signature tenofovir mutation
• D Dolutegravir — integrase strand transfer inhibitor, not affected by RT mutations

Explanation

M184V is the signature resistance mutation for the nucleoside reverse transcriptase inhibitors lamivudine (3TC) and emtricitabine (FTC), conferring high-level resistance (>1000-fold increase in MIC). Paradoxically, M184V impairs viral fitness and increases sensitivity to zidovudine (AZT) and tenofovir, which is sometimes exploited in salvage therapy. K103N is the primary efavirenz resistance mutation; K65R is tenofovir's signature mutation; dolutegravir is an integrase inhibitor with a completely different resistance profile.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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