As with all other anti-HIV drugs, strains of HIV that are resistant to efavirenz (Sustiva) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug. If blood levels of the drug fall too low, this will help the development of resistance to efavirenz and may affect future treatment options.

All non-nucleoside reverse transcriptase inhibitors (NNRTIs) have a low barrier to resistance, meaning that only one mutation is needed to result in a drop in the drug’s efficacy. The major mutation is K103N in the reverse transcriptase gene. Other efavirenz resistance mutations include L100I, V108I, Y188L, G190S and P225H^[1][2][3][4].

Once resistance to efavirenz has developed, the other NNRTIs nevirapine (Viramune) and delavirdine (Rescriptor), which is rarely used today, are unlikely to be effective. Similarly, patients with resistance to one of the other NNRTIs are unlikely to benefit from efavirenz. One possible exception is the Y181C mutation, which is associated with nevirapine resistance, but which may not cause resistance to efavirenz.

In some instances, response to an NNRTI-based regimen may be enhanced by the presence of certain mutations linked to nucleoside reverse transcriptase inhibitors (NRTIs)^[5]. NRTI resistance mutations including M41L, M184V, L210W and T215Y have been associated with better virological and immunological responses to efavirenz-based regimens^[6][7][8]. However, this effect may be transient and its relevance for patients remains to be established.

A genetic polymorphism in the multidrug resistance gene 1 has been associated with a reduced likelihood of efavirenz treatment failure and a decreased rate of emergence of efavirenz resistance mutations^[9].