As with all other anti-HIV drugs, strains of HIV that are resistant to FTC (emtricitabine, Emtriva) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug. HIV can rapidly develop resistance to FTC if viral load is not suppressed below the limit of detection.

The M184V/I mutation, which is associated with resistance to 3TC (lamivudine, Epivir), is also the key resistance mutation for FTC^[1]. However, this mutation develops more slowly in people taking FTC^[2].

FTC is unlikely to have anti-HIV effect in people who have already developed resistance to 3TC. However, the M184V mutation can enhance the antiviral efficacy of other drugs such as AZT (zidovudine, Retrovir), because it slows the ability of the virus to develop resistance to them. The mutation does not affect susceptibility to other nucleoside reverse transcriptase inhibitors (NRTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

No other mutations have been associated with high-level FTC resistance, including other NRTI and NNRTI mutations. However, the K65R mutation, which is associated with ddC (zalcitabine, Hivid) resistance, may slightly reduce the efficacy of FTC.