Competitive Fitness Assays Indicate that the E138A Substitution in HIV-1 Reverse Transcriptase Decreases In Vitro Susceptibility to Emtricitabine
Author(s) -
Nicolas SluisCremer,
Kelly Huber,
Chanson J. Brumme,
P. Richard Harrigan
Publication year - 2014
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02114-13
Subject(s) - etravirine , rilpivirine , emtricitabine , reverse transcriptase , virology , reverse transcriptase inhibitor , nucleoside reverse transcriptase inhibitor , tenofovir , human immunodeficiency virus (hiv) , biology , nucleoside , in vitro , lamivudine , virus , genetics , rna , antiretroviral therapy , viral load , gene , hepatitis b virus
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.
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