M184I

M184I is a substitution in the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It involves replacing methionine with isoleucine at position 184 within the YMDD motif, a catalytic region essential for viral DNA synthesis.

Clinically, M184I is associated with resistance to the nucleoside reverse transcriptase inhibitors lamivudine (3TC) and emtricitabine (FTC). It is less common and often less stable than the more frequent M184V mutation, and in many cases M184I appears as an intermediate that can revert to M184V under continued drug pressure. High‑level resistance to 3TC/FTC can be observed when M184I coexists with additional mutations, particularly M184V. The mutation typically incurs a reduction in viral replication capacity, contributing to fitness costs for the virus.

Impact on susceptibility to other antiretroviral agents is variable; some evidence suggests M184I (and M184V) may modestly influence susceptibility to zidovudine (AZT) or interact with other thymidine analogue mutations to affect overall resistance patterns. Genotypic testing identifying M184I can inform treatment decisions, especially in the context of lamivudine/emtricitabine exposure. In clinical practice, M184I is often discussed alongside M184V as part of resistance interpretation and therapy planning.