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Rilpivirine is listed as a recommended or alternative key drug in the current ART guidelines. E138K in HIV-1 reverse transcriptase (RT) is a primary mutation in resistance to rilpivirine, although in vitro experiments showed it confers only &lt;3-fold resistance. An unidentified mechanism could amplify resistance to rilpivirine conferred by E138K.

Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations