title: Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.
abstract: We characterized the relative fitness of multiple nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistant HIV-1 variants in the presence of etravirine (ETV), rilpivirine (RPV), and/or the nucleoside RT inhibitor emtricitabine (FTC) by simultaneous competitive culture and 454 deep sequencing. The E138A substitution, typically associated with decreased virologic responses to ETV- and RPV-containing regimens, confers a clear fitness advantage to the virus in the presence of FTC and decreases FTC susceptibility 4.7-fold.
authors.affiliation: University of Pittsburgh, Department of Medicine, Division of Infectious Diseases, Pittsburgh, Pennsylvania, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Huber
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics; D000068679:Emtricitabine; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D003841:Deoxycytidine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068679:Emtricitabine