Biochemical mechanism of HIV-1 resistance to rilpivirine

Kamalendra Singh, Bruno Marchand, Devendra K. Rai, Bechan Sharma, Eleftherios Michailidis, Emily M. Ryan, Kayla B. Matzek, Maxwell D. Leslie, Ariel N. Hagedorn, Zhe Li, Pieter R. Norden, Atsuko Hachiya, Michael A. Parniak, Hong Tao Xu, Mark A. Wainberg, Stefan G. Sarafianos

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Background: Reverse transcriptase mutations E138K and M184I emerged most frequently in HIV-1 patients who failed rilpivirine/emtricitabine/tenofovir combination therapy. Results: M184I reduces polymerase efficiency, and E138K restores it. E138K also reduces rilpivirine binding affinity mainly by increasing its dissociation rate. Conclusion: E138K abrogates the polymerase defect of M184I and increases rilpivirine dissociation. Significance: Our results provide a biochemical explanation for the selection of E138K/M184I in patients who failed combination therapy.

Original languageEnglish (US)
Pages (from-to)38110-38123
Number of pages14
JournalJournal of Biological Chemistry
Issue number45
StatePublished - Nov 2 2012

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