An HIV patient has a plasma viral load of 180,000 copies/mL and CD4 count of 250/µL at baseline. After 6 months on TDF + 3TC + EFV, viral load remains at 95,000 copies/mL. Resistance testing reveals M184V mutation. What is the significance of M184V in clinical management?
- A M184V confers resistance to tenofovir and requires boosted PI switch
- B M184V confers resistance to all NRTIs including TDF
- C M184V confers high-level resistance to lamivudine (3TC) and emtricitabine (FTC) but hypersensitises to tenofovir ✓
- D M184V is a polymorphism unrelated to treatment failure
Explanation
The M184V mutation in reverse transcriptase is the signature resistance mutation selected by 3TC and FTC, conferring >100-fold resistance to both. However, M184V also decreases viral fitness and paradoxically increases susceptibility to tenofovir and zidovudine (reverse phenotype), which is why some regimens intentionally retain 3TC even in M184V-detected virological failure to maintain this fitness cost. Regimen switch should address the cause of failure—in this case, evaluating EFV susceptibility and considering DTG-based second-line is appropriate per WHO guidelines.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.