title: Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine.
abstract: The contribution of E138 mutations to etravirine resistance was investigated. Amino acids at position E138 after failure with etravirine in DUET were A (n = 1), G (n = 5), K (n = 3), P (n = 1), Q (n = 5), and V (n = 2). At baseline, only E138A and Q were found at 3.0% and 2.5%, respectively. Virologic response (less than 50 copies/mL) was observed in six of 12 and eight of 10 patients with E138A and E138Q, respectively. Site-directed mutants harboring E138A/G/K/Q/R or S showed etravirine fold change values of 2.9, 2.4, 2.6, 3.0, 3.6, and 2.8, respectively. E138G, K, and Q were added to the existing etravirine-weighted genotypic score including 17 etravirine resistance-associated mutations.
authors.affiliation: Tibotec BVBA, Beerse, Belgium.
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: Steven
authors.initials: S
authors.lastname: Nijs
authors.forename: Bjorn
authors.initials: B
authors.lastname: Daems
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D009570:Nitriles; D010641:Phenotype; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase