title: Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States.
abstract: Abstract   The prevalence of susceptibility to etravirine was investigated among clinical samples submitted for routine clinical testing in the United States using two separate weighted genotypic scoring systems. The presence of etravirine mutations and susceptibility to etravirine by phenotype of clinical samples from HIV-1-infected patients, submitted to Monogram Biosciences for routine resistance testing between June 2008 and June 2009, were analyzed. Susceptibility by genotype was determined using the Monogram and Tibotec etravirine-weighted genotypic scoring systems, with scores of ≤3 and ≤2, respectively, indicating full susceptibility. Susceptibility by phenotype was determined using the PhenoSense HIV assay, with lower and higher clinical cut-offs of 2.9 and 10, respectively. The frequency of individual etravirine mutations and the impact of the K103N mutation on susceptibility to etravirine by genotype were also determined. Among the 5482 samples with ≥1 defined nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations associated with resistance, 67% were classed as susceptible to etravirine by genotype by both scoring systems. Susceptibility to etravirine by phenotype was higher (76%). The proportion of first-generation NNRTI-resistant samples with (n=3598) and without (n=1884) K103N with susceptibility to etravirine by genotype was 77% and 49%, respectively. Among samples susceptible to first-generation NNRTIs (n=9458), >99% of samples were susceptible to etravirine by phenotype (FC <2.9); the remaining samples had FC ≥2.9-10. In summary, among samples submitted for routine clinical testing in the United States, a high proportion of samples with first-generation NNRTI resistance was susceptible to etravirine by genotype and phenotype. A higher proportion of NNRTI-resistant samples with K103N than without was susceptible to etravirine.
authors.affiliation: Tibotec Inc ., Titusville, New Jersey 08560, USA. gpicchio@its.jnj.com
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: Eoin
authors.initials: E
authors.lastname: Coakley
authors.forename: Mojgan
authors.initials: M
authors.lastname: Haddad
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D009570:Nitriles; D010641:Phenotype; D015995:Prevalence; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine